O tratamento para o câncer de mama invasivo primário é complexo e altamente individualizado e leva em consideração diferentes fatores, como idade, capacidade funcional, estádio da doença, tipo de tumor, biologia do tumor (por exemplo, status para receptor de hormônio [HR], status para HER2, perfil genético) e prognóstico (risco de recidiva).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[163]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[203]Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. 2017 Aug 1;28(8):1700-12.
https://www.annalsofoncology.org/article/S0923-7534(19)32181-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/28838210?tool=bestpractice.com
Há diferenças na abordagem para pacientes com câncer de mama em estádio inicial (estádios I a IIB [T2 N1 M0]) e para pacientes com câncer de mama localmente avançado (estádios IIB [T3 N0 M0] a III, incluindo câncer de mama inflamatório).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Os objetivos do tratamento são:
Alcançar esses objetivos exige uma abordagem de tratamento multimodal que pode incluir um ou mais dos seguintes:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Ressecção cirúrgica do tumor primário (por exemplo, mastectomia total ou lumpectomia [cirurgia conservadora da mama])
Estadiamento cirúrgico dos linfonodos axilares (por exemplo, biópsia de linfonodo sentinela [BLS] ou dissecção dos linfonodos axilares [DLA])
Quimioterapia
Radioterapia
Terapia endócrina (para doença positiva para HR)
Terapia direcionada para HER2 (para doença positiva para HER2)
Inibidor de quinase (abemaciclibe ou ribociclibe) para doença HR-positiva e HER2-negativa
Inibidor de poli (adenosina difosfato-ribose) polimerase (PARP) (olaparibe) para câncer de mama negativo para HER2
Imunoterapia (pembrolizumabe, um anticorpo monoclonal bloqueador do receptor da proteína de morte celular programada 1 [PD-1]) para câncer de mama triplo negativo (isto é, negativo para HR e negativo para HER2).
As pacientes são mais bem tratadas por uma equipe multidisciplinar de especialistas em câncer de mama, composta de oncologistas, cirurgiões, rádio-oncologistas, radiologistas, patologistas e enfermeiros.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
As pacientes devem ser envolvidas na tomada de decisão e no plano de tratamento durante todo o ciclo do tratamento.
O aconselhamento genético é recomendado para mulheres com alto risco de câncer de mama hereditário. O impacto do tratamento para câncer de mama sobre a fertilidade deve ser discutido com mulheres em idade reprodutiva.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
Câncer de mama em estádio inicial (estádios I a IIB [T2 N1 M0])
Geralmente, o tratamento inicial para câncer de mama em estádio inicial é a cirurgia primária da mama (por exemplo, lumpectomia ou mastectomia total) com estadiamento cirúrgico do linfonodo axilar (por exemplo, BLS com ou sem DLA).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Os pacientes também podem receber tratamento sistêmico adjuvante (pós-operatório) (por exemplo, quimioterapia; terapia endócrina; terapia direcionada a HER2; inibidor de quinase para doença positiva para HR, negativa para HER2; inibidor de PARP para doença negativa para HER2; imunoterapia para doença triplo-negativa) após a cirurgia, dependendo do estágio da doença, idade, capacidade funcional/condição física e outros fatores prognósticos.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[204]Korde LA, Somerfield MR, Hershman DL, et al. Use of immune checkpoint inhibitor pembrolizumab in the treatment of high-risk, early-stage triple-negative breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2022 May 20;40(15):1696-8.
https://ascopubs.org/doi/full/10.1200/JCO.22.00503
http://www.ncbi.nlm.nih.gov/pubmed/35417251?tool=bestpractice.com
[205]Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810-21.
https://www.nejm.org/doi/10.1056/NEJMoa1910549
http://www.ncbi.nlm.nih.gov/pubmed/32101663?tool=bestpractice.com
[206]Tung NM, Zakalik D, Somerfield MR, et al. Adjuvant PARP inhibitors in patients with high-risk early-stage HER2-negative breast cancer and germline BRCA mutations: ASCO hereditary breast cancer guideline rapid recommendation update. J Clin Oncol. 2021 Sep 10;39(26):2959-61.
https://ascopubs.org/doi/full/10.1200/JCO.21.01532
http://www.ncbi.nlm.nih.gov/pubmed/34343058?tool=bestpractice.com
[207]Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021 Jun 24;384(25):2394-405.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126186
http://www.ncbi.nlm.nih.gov/pubmed/34081848?tool=bestpractice.com
[208]Emens LA, Adams S, Cimino-Mathews A, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. J Immunother Cancer. 2021 Aug;9(8):e002597.
https://jitc.bmj.com/content/9/8/e002597.long
http://www.ncbi.nlm.nih.gov/pubmed/34389617?tool=bestpractice.com
[209]Freedman RA, Caswell-Jin JL, Hassett M, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-cyclin-dependent kinase 4 and 6 inhibitors: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2024 Jun 20;42(18):2233-5.
https://ascopubs.org/doi/10.1200/JCO.24.00886
http://www.ncbi.nlm.nih.gov/pubmed/38768407?tool=bestpractice.com
Certos pacientes com câncer de mama em estágio inicial devem ser considerados para tratamento sistêmico neoadjuvante (pré-operatório), incluindo aqueles com:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Doença triplo negativa ou doença positiva para HER2 com linfonodos positivos e/ou tumores grandes (isto é, >2 cm)
Tumor primário grande em relação ao tamanho da mama que desejam conservar a mama
Doença linfonodal clinicamente positiva com probabilidade de tornar-se clinicamente negativa com terapia sistêmica neoadjuvante
Atraso antes da cirurgia (por exemplo, para o teste genético ou para considerar opções de reconstrução).
O tratamento neoadjuvante também pode ser considerado para algumas pessoas com doença triplo negativa ou doença positiva para HER2 que apresentam linfonodos negativos e tumores >1 cm.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A radioterapia é fortemente recomendada após a lumpectomia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[Evidência B]da6369d0-1e2b-4750-9ece-6b7a1ad71821guidelineBQuais são os efeitos da radioterapia de mama completa, comparada com nenhuma radioterapia para mulheres com câncer de mama invasivo primário após a lumpectomia?[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
A radioterapia pode ser considerada após a mastectomia total em determinadas pacientes de alto risco.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[Evidência B]21535362-2349-4940-9adc-543a680536abguidelineBQuais são os efeitos da radioterapia de mama completa, comparada com nenhuma radioterapia para mulheres com câncer de mama invasivo primário após a mastectomia?[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
O tipo e a extensão da radioterapia são guiados por vários fatores (por exemplo, extensão do envolvimento linfonodal e margens de ressecção do tumor) e são individualizados para a paciente.
Os tratamentos sistêmicos e a radioterapia são as principais opções de tratamento para as pacientes que não são adequadas para cirurgia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
Câncer de mama localmente avançado (estádios IIB [T3 N0 M0] a III)
Geralmente, o tratamento inicial para câncer de mama localmente avançado é a quimioterapia (pré-operatória) neoadjuvante (combinada com terapia neoadjuvante direcionada para HER2, para aquelas com doença positiva para HER2), seguida por mastectomia total com DLA (isto é, mastectomia radical modificada).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
As pacientes com câncer de mama avançado local clinicamente negativo para linfonodos (por exemplo, T3 N0 M0) podem ser submetidas a BLS ao invés da DLA.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A radioterapia é recomendada após a mastectomia, principalmente para pacientes com alto risco de recidiva.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[Evidência B]21535362-2349-4940-9adc-543a680536abguidelineBQuais são os efeitos da radioterapia de mama completa, comparada com nenhuma radioterapia para mulheres com câncer de mama invasivo primário após a mastectomia?[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Algumas pacientes que respondem bem ao tratamento sistêmico neoadjuvante podem ser consideradas para lumpectomia associada à radioterapia de mama completa em vez de mastectomia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[Evidência A]057d9bdb-ac74-43c7-9201-8ebfb4ae4c25guidelineAQual é a eficácia da quimioterapia neoadjuvante para adultos com câncer de mama invasivo primário?[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
As pacientes com doença positiva para HR também devem receber terapia endócrina por um mínimo de 5 anos, a qual geralmente é administrada após a cirurgia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Para doença positiva para HER2, a terapia endócrina deve ser combinada com terapia direcionada para HER2 para completar 12 meses de terapia direcionada para HER2. Para pacientes com doença triplo-negativa que receberam pembrolizumabe neoadjuvante, a terapia adjuvante com pembrolizumabe deve ser mantida.[205]Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810-21.
https://www.nejm.org/doi/10.1056/NEJMoa1910549
http://www.ncbi.nlm.nih.gov/pubmed/32101663?tool=bestpractice.com
O abemaciclibe ou o ribociclibe podem ser considerados em combinação com terapia endócrina para as pacientes com câncer de mama inicial HR-positivo e HER2-negativo com alto risco de recorrência.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[209]Freedman RA, Caswell-Jin JL, Hassett M, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-cyclin-dependent kinase 4 and 6 inhibitors: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2024 Jun 20;42(18):2233-5.
https://ascopubs.org/doi/10.1200/JCO.24.00886
http://www.ncbi.nlm.nih.gov/pubmed/38768407?tool=bestpractice.com
[210]Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-98.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339
http://www.ncbi.nlm.nih.gov/pubmed/32954927?tool=bestpractice.com
Lumpectomia ou mastectomia total
As pacientes com câncer de mama em estádio inicial podem escolher entre a lumpectomia ou a mastectomia total.[211]Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med. 2002 Oct 17;347(16):1233-41.
https://www.nejm.org/doi/full/10.1056/NEJMoa022152
http://www.ncbi.nlm.nih.gov/pubmed/12393820?tool=bestpractice.com
Geralmente, a lumpectomia seguida por radioterapia total da mama (ou irradiação parcial acelerada da mama/irradiação parcial da mama [IPAM/PAM], em algumas pacientes de baixo risco) é preferível à mastectomia para câncer de mama em estádio inicial, dependendo da localização do tumor, da extensão da doença e do tamanho da mama afetada. No entanto, existem contraindicações absolutas e relativas à lumpectomia que necessita de radioterapia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Entre as contraindicações absolutas estão:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Gravidez (no entanto, caso a lumpectomia seja realizada no terceiro trimestre [ou no segundo trimestre seguida por quimioterapia adjuvante] isso pode permitir o adiamento da radioterapia até depois do parto)
Margens patológicas difusamente positivas
Homozigose (inativação bialélica) para mutação em ATM
Microcalcificações difusas suspeitas ou de aparência maligna
Doença disseminada que não pode ser incorporada por excisão local de uma única região ou segmento de tecido mamário que atinge margens negativas com resultado cosmético satisfatório.
As contraindicações relativas incluem:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Radioterapia prévia na mama ou parede torácica (o conhecimento das doses e volumes prescritos é essencial)
Doença do tecido conjuntivo ativa envolvendo a pele (por exemplo, lúpus eritematoso sistêmico, esclerodermia)
Margens patológicas positivas
Risco genético de câncer de mama conhecido ou suspeito.
Contraindicações à lumpectomia, como doença disseminada e microcalcificações difusas, podem ser avaliadas de maneira mais completa com o uso de ressonância nuclear magnética (RNM) da mama e biópsia guiada por RNM (necessária caso as lesões só possam ser observadas por RNM). As pacientes com microcalcificações difusas devem fazer biópsias adicionais para avaliar a extensão da doença. As pacientes com doença não limitada a um único quadrante ou que têm mamas maiores podem, em alguns casos, ser tratadas com lumpectomia.
Uma re-excisão é recomendada para as pacientes com margem positiva ("tinta no tumor"; 0 mm) após uma lumpectomia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[212]Moran MS, Schnitt SJ, Giuliano AE, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. J Clin Oncol. 2014 May 10;32(14):1507-15.
https://ascopubs.org/doi/10.1200/JCO.2013.53.3935
http://www.ncbi.nlm.nih.gov/pubmed/24516019?tool=bestpractice.com
[213]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jan 2024 [internet publication].
https://www.nice.org.uk/guidance/ng101
A taxa de re-excisão para margens positivas após uma lumpectomia é de 14%.[214]Havel L, Naik H, Ramirez L, et al. Impact of the SSO-ASTRO margin guideline on rates of re-excision after lumpectomy for breast cancer: a meta-analysis. Ann Surg Oncol. 2019 May;26(5):1238-44.
http://www.ncbi.nlm.nih.gov/pubmed/30790112?tool=bestpractice.com
O risco de recorrência local pode aumentar nas pacientes com margens estreitas.[215]Bundred JR, Michael S, Stuart B, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. BMJ. 2022 Sep 21;378:e070346.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9490551
http://www.ncbi.nlm.nih.gov/pubmed/36130770?tool=bestpractice.com
Portanto, algumas diretrizes recomendam a consideração de cirurgia adicional se houver margens estreitas (por exemplo, >0 mm e <1 mm ou <2 mm), com as decisões individualizadas sobre tratamento adicional tomadas por meio de tomada de decisão compartilhada.[213]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jan 2024 [internet publication].
https://www.nice.org.uk/guidance/ng101
[216]The American Society of Breast Surgeons. Resource guide on breast cancer: breast conservation surgery margins. 2024 [internet publication].
https://www.breastsurgeons.org/docs/statements/ASBrS-Resource-Guide-on-Breast-Cancer-Breast-Conservation-Surgery-Margins.pdf
Geralmente, a mastectomia total com DLA (após o tratamento sistêmico neoadjuvante) é recomendada para as pacientes com câncer de mama localmente avançado, principalmente para aquelas com câncer de mama inflamatório.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
No entanto, alguns pacientes que respondem bem ao tratamento sistêmico neoadjuvante podem ser elegíveis para tumorectomia com amostragem de linfonodo sentinela seguida por radioterapia de toda a mama.
Gestação
Evidências sugerem que gestantes com câncer de mama em estádio inicial e localmente avançado podem ser tratadas com segurança com lumpectomia e quimioterapia neoadjuvante ou adjuvante (por exemplo, antraciclinas ou agentes alquilantes) no segundo ou terceiro trimestre.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[217]Kuerer HM, Gwyn K, Ames FC, et al. Conservative surgery and chemotherapy for breast carcinoma during pregnancy. Surgery. 2002 Jan;131(1):108-10.
http://www.ncbi.nlm.nih.gov/pubmed/11812971?tool=bestpractice.com
[218]Framarino-Dei-Malatesta M, Sammartino P, Napoli A. Does anthracycline-based chemotherapy in pregnant women with cancer offer safe cardiac and neurodevelopmental outcomes for the developing fetus? BMC Cancer. 2017 Nov 21;17(1):777.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696726
http://www.ncbi.nlm.nih.gov/pubmed/29162041?tool=bestpractice.com
[219]Germann N, Goffinet F, Goldwasser F. Anthracyclines during pregnancy: embryo-fetal outcome in 160 patients. Ann Oncol. 2004 Jan;15(1):146-50.
https://www.annalsofoncology.org/article/S0923-7534(19)61524-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/14679135?tool=bestpractice.com
[220]Murthy RK, Theriault RL, Barnett CM, et al. Outcomes of children exposed in utero to chemotherapy for breast cancer. Breast Cancer Res. 2014 Dec 30;16(6):500.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303207
http://www.ncbi.nlm.nih.gov/pubmed/25547133?tool=bestpractice.com
As terapias adjuvantes direcionadas ao HER2 e/ou endócrinas e a radioterapia são adiadas até depois do parto.
Reconstrução da mama
A reconstrução mamária deve ser discutida com todas as pacientes antes da cirurgia de mama. A reconstrução da mama pode ser realizada na cirurgia inicial ou pode ser protelada, mas o momento não deve interferir no tratamento cirúrgico adequado. O provável desfecho cosmético deve ser avaliado antes da cirurgia conservadora da mama; técnicas oncoplásicas podem ser consideradas para melhorar os resultados cosméticos, embora haja falta de evidências para desfechos oncológicos.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[221]Nanda A, Hu J, Hodgkinson S, et al. Oncoplastic breast-conserving surgery for women with primary breast cancer. Cochrane Database Syst Rev. 2021 Oct 29;10(10):CD013658.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013658.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/34713449?tool=bestpractice.com
[222]Rutherford CL, Barker S, Romics L. A systematic review of oncoplastic volume replacement breast surgery: oncological safety and cosmetic outcome. Ann R Coll Surg Engl. 2022 Jan;104(1):5-17.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10335172
http://www.ncbi.nlm.nih.gov/pubmed/34767472?tool=bestpractice.com
A reconstrução mamária imediata após a mastectomia não está associada a aumento da incidência de recidiva local quando comparada à mastectomia somente, desde que a remoção cirúrgica do câncer de mama não seja protelada.[223]Gieni M, Avram R, Dickson L, et al. Local breast cancer recurrence after mastectomy and immediate breast reconstruction for invasive cancer: a meta-analysis. Breast. 2012 Jun;21(3):230-6.
http://www.ncbi.nlm.nih.gov/pubmed/22225710?tool=bestpractice.com
No entanto, a reconstrução mamária imediata é contraindicada em pacientes com câncer de mama inflamatório devido à necessidade de radioterapia pós-operatória rápida.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A mastectomia preservadora de pele (com ou sem preservação do mamilo) pode melhorar a cosmese e é viável e eficaz em mulheres com câncer de mama em estádio inicial. Nenhuma diferença significativa nas taxas de recidiva local foi encontrada entre a mastectomia total e a mastectomia preservadora de pele, mas fatores como tamanho do tumor e alto grau histológico podem aumentar o risco de recidiva.[224]Newman LA, Kuerer HM, Hunt KK, et al. Presentation, treatment, and outcome of local recurrence after skin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol. 1998 Oct-Nov;5(7):620-6.
http://www.ncbi.nlm.nih.gov/pubmed/9831111?tool=bestpractice.com
[225]Medina-Franco H, Vasconez LO, Fix RJ, et al. Factors associated with local recurrence after skin-sparing mastectomy and immediate breast reconstruction for invasive breast cancer. Ann Surg. 2002 Jun;235(6):814-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422510
http://www.ncbi.nlm.nih.gov/pubmed/12035037?tool=bestpractice.com
[226]Agha RA, Al Omran Y, Wellstead G, et al. Systematic review of therapeutic nipple-sparing versus skin-sparing mastectomy. BJS Open. 2019 Apr;3(2):135-45.
https://academic.oup.com/bjsopen/article/3/2/135/6043581
http://www.ncbi.nlm.nih.gov/pubmed/30957059?tool=bestpractice.com
A mastectomia com preservação do mamilo só deve ser realizada se houver confirmação de que o mamilo está livre de tumor durante a cirurgia.
As mulheres com mutações BRCA1 ou BRCA2 na linha germinativa podem ser tratadas com terapia conservadora da mama.[227]Tung NM, Boughey JC, Pierce LJ, et al. Management of hereditary breast cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology guideline. J Clin Oncol. 2020 Jun 20;38(18):2080-106.
https://ascopubs.org/doi/10.1200/JCO.20.00299
http://www.ncbi.nlm.nih.gov/pubmed/32243226?tool=bestpractice.com
As diretrizes recomendam discutir os riscos relativos e os benefícios da terapia conservadora da mama versus mastectomia redutora de risco contralateral ou ipsilateral terapêutica. A mastectomia preservadora de mamilo é apropriada. As considerações incluem a idade no momento do diagnóstico, que representa o preditor mais forte de câncer de mama contralateral no futuro, comorbidades e expectativa de vida da paciente, história familiar de câncer de mama, prognóstico geral do câncer de mama e outros cânceres e a capacidade da paciente de se submeter a uma RNM de rastreamento.[227]Tung NM, Boughey JC, Pierce LJ, et al. Management of hereditary breast cancer: American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology guideline. J Clin Oncol. 2020 Jun 20;38(18):2080-106.
https://ascopubs.org/doi/10.1200/JCO.20.00299
http://www.ncbi.nlm.nih.gov/pubmed/32243226?tool=bestpractice.com
Tabagismo, obesidade, mama de tamanho maior e diabetes podem aumentar as taxas de complicação associadas à reconstrução mamária (por exemplo, complicações na cura da lesão, falha do retalho); portanto, as pacientes devem ser bem informadas e avaliadas da maneira adequada.[228]Sadok N, Krabbe-Timmerman IS, de Bock GH, et al. The effect of smoking and body mass index on the complication rate of alloplastic breast reconstruction. Scand J Surg. 2020 Jun;109(2):143-50.
http://www.ncbi.nlm.nih.gov/pubmed/30712467?tool=bestpractice.com
[229]O'Neill AC, Sebastiampillai S, Zhong T, et al. Increasing body mass index increases complications but not failure rates in microvascular breast reconstruction: a retrospective cohort study. J Plast Reconstr Aesthet Surg. 2019 Sep;72(9):1518-24.
http://www.ncbi.nlm.nih.gov/pubmed/31196805?tool=bestpractice.com
[230]Duggal CS, Grudziak J, Metcalfe DB, et al. The effects of breast size in unilateral postmastectomy breast reconstruction. Ann Plast Surg. 2013 May;70(5):506-12.
http://www.ncbi.nlm.nih.gov/pubmed/23542837?tool=bestpractice.com
[231]Hart A, Funderburk CD, Chu CK, et al. The impact of diabetes mellitus on wound healing in breast reconstruction. Ann Plast Surg. 2017 Mar;78(3):260-3.
http://www.ncbi.nlm.nih.gov/pubmed/27505449?tool=bestpractice.com
Geralmente, a reconstrução da mama é seguida de um enxerto de gordura autóloga, que é um procedimento eletivo em que a gordura retirada por lipossucção do abdome ou das coxas é injetada na mama reconstruída para melhorar a cosmese. O enxerto de gordura autóloga não está associado ao aumento do risco de recorrência locorregional.[232]Wang K, Dai Y, Pan Y, et al. Local-regional recurrence risk after autologous fat grafting in breast cancer patients: a systematic review and meta-analysis. J Surg Oncol. 2020 Mar;121(3):435-40.
http://www.ncbi.nlm.nih.gov/pubmed/31943238?tool=bestpractice.com
Esse procedimento está associado ao risco de desenvolver necrose gordurosa.
Estadiamento cirúrgico dos linfonodos axilares
O envolvimento do linfonodo axilar é um fator prognóstico importante nas pacientes com câncer de mama. As pacientes devem ser submetidas a uma avaliação clínica completa da axila antes da cirurgia. Esta pode incluir exame clínico da região axilar, ultrassonografia, RNM da mama ou biópsia de linfonodos suspeitos guiada por US.
A BLS é um procedimento cirúrgico seguro e acurado para avaliar os linfonodos axilares no câncer de mama em estádio inicial.[233]Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003 Aug 7;349(6):546-53.
https://www.nejm.org/doi/full/10.1056/NEJMoa012782
http://www.ncbi.nlm.nih.gov/pubmed/12904519?tool=bestpractice.com
[234]Veronesi U, Viale G, Paganelli G, et al. Sentinel lymph node biopsy in breast cancer: ten-year results of a randomized controlled study. Ann Surg. 2010 Apr;251(4):595-600.
http://www.ncbi.nlm.nih.gov/pubmed/20195151?tool=bestpractice.com
[235]Glechner A, Wöckel A, Gartlehner G, et al. Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis. Eur J Cancer. 2013 Mar;49(4):812-25.
http://www.ncbi.nlm.nih.gov/pubmed/23084155?tool=bestpractice.com
[236]Solá M, Alberro JA, Fraile M, et al. Complete axillary lymph node dissection versus clinical follow-up in breast cancer patients with sentinel node micrometastasis: final results from the multicenter clinical trial AATRM 048/13/2000. Ann Surg Oncol. 2013 Jan;20(1):120-7.
http://www.ncbi.nlm.nih.gov/pubmed/22956062?tool=bestpractice.com
[237]Krag DN, Anderson SJ, Julian TB, et al. Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial. Lancet Oncol. 2010 Oct;11(10):927-33.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041644
http://www.ncbi.nlm.nih.gov/pubmed/20863759?tool=bestpractice.com
[238]Julian TB, Anderson SJ, Krag DN, et al. 10-yr follow-up results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients. Paper presented at: 2013 ASCO Annual Meeting I. J Clin Oncol. 2013 May 20:31(15 suppl):1000.
https://ascopubs.org/doi/abs/10.1200/jco.2013.31.15_suppl.1000
[239]Mansel RE, Fallowfield L, Kissin M, et al. Randomized multicenter trial of sentinel node biopsy versus standard axillary treatment in operable breast cancer: the ALMANAC Trial. J Natl Cancer Inst. 2006 May 3;98(9):599-609.
https://academic.oup.com/jnci/article/98/9/599/2522073
http://www.ncbi.nlm.nih.gov/pubmed/16670385?tool=bestpractice.com
[240]Bromham N, Schmidt-Hansen M, Astin M, et al. Axillary treatment for operable primary breast cancer. Cochrane Database Syst Rev. 2017 Jan 4;1(1):CD004561.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004561.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/28052186?tool=bestpractice.com
Envolve a identificação, remoção e exame do(s) linfonodo(s) sentinela(s) (SLNs) para a presença de metástases. É menos invasiva que a DLA e causa menos complicações (por exemplo, linfedema).[233]Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. N Engl J Med. 2003 Aug 7;349(6):546-53.
https://www.nejm.org/doi/full/10.1056/NEJMoa012782
http://www.ncbi.nlm.nih.gov/pubmed/12904519?tool=bestpractice.com
[235]Glechner A, Wöckel A, Gartlehner G, et al. Sentinel lymph node dissection only versus complete axillary lymph node dissection in early invasive breast cancer: a systematic review and meta-analysis. Eur J Cancer. 2013 Mar;49(4):812-25.
http://www.ncbi.nlm.nih.gov/pubmed/23084155?tool=bestpractice.com
Não se deve usar a BLS rotineiramente em mulheres com linfonodos clinicamente negativos com idade igual ou superior a 70 anos com câncer de mama invasivo em estádio inicial, negativo para HER2 e positivo para HR.[241]Choosing Wisely; Society of Surgical Oncology. Five things physicians and patients should question. Jul 2021 [internet publication].
https://www.choosingwisely.org/wp-content/uploads/2016/07/SSO-5things-List_2021-Updates.pdf
Pacientes clinicamente negativas para linfonodos
Em pacientes com câncer de mama em estádio inicial com linfonodos clinicamente negativos ou que apresentam 1 ou 2 linfonodos suspeitos no exame de imagem, uma BLS deve ser realizada durante a cirurgia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[242]Schwartz GF, Giuliano AE, Veronesi U. Proceedings of the consensus conference on the role of sentinel lymph node biopsy in carcinoma of the breast, April 19-22, 2001, Philadelphia, Pennsylvania. Cancer. 2002 May 15;94(10):2542-51.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.10539
http://www.ncbi.nlm.nih.gov/pubmed/12173319?tool=bestpractice.com
[243]Park KU, Somerfield MR, Anne N, et al. Sentinel lymph node biopsy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2025 May 10;43(14):1720-41.
https://ascopubs.org/doi/10.1200/JCO-25-00099
http://www.ncbi.nlm.nih.gov/pubmed/40209128?tool=bestpractice.com
A DLA não é recomendada se a BLS for negativa.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[243]Park KU, Somerfield MR, Anne N, et al. Sentinel lymph node biopsy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2025 May 10;43(14):1720-41.
https://ascopubs.org/doi/10.1200/JCO-25-00099
http://www.ncbi.nlm.nih.gov/pubmed/40209128?tool=bestpractice.com
Na maioria dos casos, caso os linfonodos sentinelas não possam ser identificados, a dissecção axilar de níveis I e II é recomendada para o estadiamento.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Pacientes com 1 ou 2 LSs positivos submetidas a lumpectomia podem evitar a DLA se a radioterapia de mamam total estiver planejada após a cirurgia.[243]Park KU, Somerfield MR, Anne N, et al. Sentinel lymph node biopsy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2025 May 10;43(14):1720-41.
https://ascopubs.org/doi/10.1200/JCO-25-00099
http://www.ncbi.nlm.nih.gov/pubmed/40209128?tool=bestpractice.com
[244]Giuliano AE, McCall L, Beitsch P, et al. Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons Oncology Group z0011 randomized trial. Ann Surg. 2010 Sep;252(3):426-32.
http://www.ncbi.nlm.nih.gov/pubmed/20739842?tool=bestpractice.com
[245]Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011 Feb 9;305(6):569-75.
http://www.ncbi.nlm.nih.gov/pubmed/21304082?tool=bestpractice.com
[246]Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017 Sep 12;318(10):918-26.
https://jamanetwork.com/journals/jama/fullarticle/2653737
http://www.ncbi.nlm.nih.gov/pubmed/28898379?tool=bestpractice.com
Para pacientes com 1 ou 2 LSs positivos submetidas a mastectomia, a radioterapia adjuvante que inclui a axila não dissecada com risco (com ou sem irradiação de linfonodos regionais [ILR]) pode ser considerada como uma alternativa à DLA.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[247]Donker M, van Tienhoven G, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014 Nov;15(12):1303-10.
http://www.ncbi.nlm.nih.gov/pubmed/25439688?tool=bestpractice.com
[248]Sávolt Á, Péley G, Polgár C, et al. Eight-year follow up result of the OTOASOR trial: the Optimal Treatment Of the Axilla - Surgery Or Radiotherapy after positive sentinel lymph node biopsy in early-stage breast cancer: a randomized, single centre, phase III, non-inferiority trial. Eur J Surg Oncol. 2017 Apr;43(4):672-9.
http://www.ncbi.nlm.nih.gov/pubmed/28139362?tool=bestpractice.com
A BLS pode ser considerada nas pacientes com câncer de mama localmente avançado clinicamente negativo para linfonodos (por exemplo, T3 N0 M0).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Pacientes clinicamente positivas para linfonodos
Em pacientes com câncer de mama em estádio inicial com linfonodos clinicamente suspeitos (palpáveis) ou com 3 ou mais linfonodos suspeitos no exame de imagem, uma biópsia (aspiração com agulha fina [AAF] ou biópsia percutânea com agulha grossa) dos linfonodos axilares deve ser realizada para confirmar o envolvimento linfonodal.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Caso a biópsia seja positiva, recomenda-se realizar DLA.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Caso a biópsia seja negativa, a BLS é recomendada para determinar se a cirurgia axilar é necessária.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A DLA geralmente é recomendada para pacientes com câncer de mama localmente local clinicamente positivo para linfonodos e com câncer de mama inflamatório.[243]Park KU, Somerfield MR, Anne N, et al. Sentinel lymph node biopsy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2025 May 10;43(14):1720-41.
https://ascopubs.org/doi/10.1200/JCO-25-00099
http://www.ncbi.nlm.nih.gov/pubmed/40209128?tool=bestpractice.com
[249]Filippakis GM, Zografos G. Contraindications of sentinel lymph node biopsy: are there any really? World J Surg Oncol. 2007 Jan 29;5:10.
https://wjso.biomedcentral.com/articles/10.1186/1477-7819-5-10
http://www.ncbi.nlm.nih.gov/pubmed/17261174?tool=bestpractice.com
[250]Gropper AB, Calvillo KZ, Dominici L, et al. Sentinel lymph node biopsy in pregnant women with breast cancer. Ann Surg Oncol. 2014 Aug;21(8):2506-11.
http://www.ncbi.nlm.nih.gov/pubmed/24756813?tool=bestpractice.com
[251]Giammarile F, Alazraki N, Aarsvold JN, et al. The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer. Eur J Nucl Med Mol Imaging. 2013 Dec;40(12):1932-47.
http://www.ncbi.nlm.nih.gov/pubmed/24085499?tool=bestpractice.com
A terapia sistêmica neoadjuvante demonstrou reduzir o estádio de pacientes com linfonodos axilares clinicamente positivos e deve ser considerada em casos com necessidade de dissecção axilar extensa.[252]Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med. 2022 Feb 10;386(6):556-67.
https://www.nejm.org/doi/10.1056/NEJMoa2112651
http://www.ncbi.nlm.nih.gov/pubmed/35139274?tool=bestpractice.com
[253]Swain SM, Miles D, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020 Apr;21(4):519-30.
http://www.ncbi.nlm.nih.gov/pubmed/32171426?tool=bestpractice.com
[254]Rastogi P, Anderson SJ, Bear HD, et al. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008 Feb 10;26(5):778-85.
http://www.ncbi.nlm.nih.gov/pubmed/18258986?tool=bestpractice.com
Estadiamento axilar após a quimioterapia neoadjuvante no câncer de mama positivo para linfonodos
Envolve cirurgia do linfonodo sentinela, DLA e/ou radiação axilar. Isso depende da extensão do envolvimento ganglionar antes da terapia neoadjuvante.
Pacientes com doença N2 ou N3 no momento do diagnóstico devem ser tratadas com DLA, independente da resposta à terapia, seguida de radiação linfonodal. Em uma metanálise, a dissecção axilar direcionada (BLS associada à excisão de um linfonodo positivo marcado por terapia neoadjuvante) pareceu ser mais precisa para o estadiamento axilar após a terapia neoadjuvante que qualquer uma dessas intervenções isolada.[255]Simons JM, van Nijnatten TJA, van der Pol CC, et al. Diagnostic accuracy of different surgical procedures for axillary staging after neoadjuvant systemic therapy in node-positive breast cancer: a systematic review and meta-analysis. Ann Surg. 2019 Mar;269(3):432-42.
https://journals.lww.com/annalsofsurgery/Fulltext/2019/03000/Diagnostic_Accuracy_of_Different_Surgical.10.aspx
http://www.ncbi.nlm.nih.gov/pubmed/30312200?tool=bestpractice.com
Pacientes altamente selecionadas, que se tornam clinicamente negativas para linfonodos após a terapia sistêmica pré-operatória, podem ser consideradas para BLS. A adição de disseção axilar direcionada pode reduzir a taxa de resultados falso-negativos, em comparação com a BLS isolada.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Estadiamento axilar durante a gestação
O uso da BLS durante a gestação é controverso, devido à possível toxicidade fetal associada aos traçadores radioativos e à possível anafilaxia (e danos ao feto) associada ao corante azul.[256]Khera SY, Kiluk JV, Hasson DM, et al. Pregnancy-associated breast cancer patients can safely undergo lymphatic mapping. Breast J. 2008 May-Jun;14(3):250-4.
http://www.ncbi.nlm.nih.gov/pubmed/18476883?tool=bestpractice.com
O uso de traçadores radioativos (por exemplo, coloide de enxofre com tecnécio 99) é considerado seguro, mas o uso do azul isosulfan e do azul de metileno não é recomendado.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[257]Gentilini O, Cremonesi M, Trifirò G, et al. Safety of sentinel node biopsy in pregnant patients with breast cancer. Ann Oncol. 2004 Sep;15(9):1348-51.
https://www.annalsofoncology.org/article/S0923-7534(19)46056-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/15319240?tool=bestpractice.com
[258]Keleher A, Wendt R 3rd, Delpassand E, et al. The safety of lymphatic mapping in pregnant breast cancer patients using Tc-99m sulfur colloid. Breast J. 2004 Nov-Dec;10(6):492-5.
http://www.ncbi.nlm.nih.gov/pubmed/15569204?tool=bestpractice.com
Terapia sistêmica neoadjuvante (pré-operatória)
Pacientes com câncer de mama localmente avançado, inoperável ou inflamatório são tratadas inicialmente com terapia sistêmica neoadjuvante.
Certos pacientes com câncer de mama em estágio inicial devem ser considerados para tratamento sistêmico neoadjuvante (pré-operatório), incluindo aqueles com:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Doença triplo negativa ou doença positiva para HER2 com linfonodos positivos e/ou tumores grandes (isto é, >2 cm)
Tumor primário grande em relação ao tamanho da mama que desejam conservar a mama
Doença linfonodal clinicamente positiva com probabilidade de tornar-se clinicamente negativa com terapia sistêmica neoadjuvante
Atraso antes da cirurgia (por exemplo, para o teste genético ou para considerar opções de reconstrução).
O tratamento neoadjuvante também pode ser considerado para doença triplo negativa ou doença positiva para HER2 com linfonodos negativos e tumores >1 cm.
Quimioterapia neoadjuvante
Amplamente utilizada para reduzir o tamanho de tumores grandes e/ou inoperáveis, para torná-los operáveis ou permitir tumorectomia, para diminuir a necessidade de DLA e para tratar o câncer de mama inflamatório.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[259]Mougalian SS, Soulos PR, Killelea BK, et al. Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015 Aug 1;121(15):2544-52.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.29348
http://www.ncbi.nlm.nih.gov/pubmed/25902916?tool=bestpractice.com
[260]Killelea BK, Yang VQ, Mougalian S, et al. Neoadjuvant chemotherapy for breast cancer increases the rate of breast conservation: results from the National Cancer Database. J Am Coll Surg. 2015 Jun;220(6):1063-9.
http://www.ncbi.nlm.nih.gov/pubmed/25868410?tool=bestpractice.com
[261]Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 2021 May 1;39(13):1485-505.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274745
http://www.ncbi.nlm.nih.gov/pubmed/33507815?tool=bestpractice.com
A histologia, o grau, o estádio e a expressão de estrogênio, progesterona e HER2 do tumor devem ser usados para orientar as decisões clínicas quanto ao uso de quimioterapia neoadjuvante.[261]Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 2021 May 1;39(13):1485-505.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274745
http://www.ncbi.nlm.nih.gov/pubmed/33507815?tool=bestpractice.com
Foi relatado que a quimioterapia neoadjuvante tem taxas similares de recidiva à distância e sobrevida global comparada à quimioterapia adjuvante em pacientes com câncer de mama em estádio inicial, mas está associada a taxas mais altas de recidiva local.[262]Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018 Jan;19(1):27-39.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30777-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29242041?tool=bestpractice.com
[263]Mieog JS, van der Hage JA, van de Velde CJ. Preoperative chemotherapy for women with operable breast cancer. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005002.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD005002.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/17443564?tool=bestpractice.com
[264]van Nes JG, Putter H, Julien JP, et al. Preoperative chemotherapy is safe in early breast cancer, even after 10 years of follow-up; clinical and translational results from the EORTC trial 10902. Breast Cancer Res Treat. 2009 May;115(1):101-13.
http://www.ncbi.nlm.nih.gov/pubmed/18484198?tool=bestpractice.com
No entanto, o desenvolvimento de tratamentos e exames de imagem e o estadiamento preciso antes da terapia provavelmente reduzem o risco de recorrência local.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Foram relatadas taxas mais altas de sobrevida livre de recidiva e lumpectomia bem-sucedida com a quimioterapia neoadjuvante, comparada à quimioterapia adjuvante em pacientes com resposta patológica completa (isto é, sem câncer invasivo na mama e nos linfonodos axilares).[265]Wolmark N, Wang J, Mamounas E, et al. Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr. 2001 Dec 1;(30):96-102.
https://academic.oup.com/jncimono/article/2001/30/96/936263
http://www.ncbi.nlm.nih.gov/pubmed/11773300?tool=bestpractice.com
[266]Esserman LJ, Berry DA, Demichele A, et al. Pathologic complete response predicts recurrence-free survival more effectively by cancer subset: results from the I-SPY 1 TRIAL - CALGB 150007/150012, ACRIN 6657. J Clin Oncol. 2012 Sep 10;30(26):3242-9.
https://ascopubs.org/doi/10.1200/JCO.2011.39.2779
http://www.ncbi.nlm.nih.gov/pubmed/22649152?tool=bestpractice.com
Esses efeitos são mais dramáticos na doença triplo negativa e na doença positiva para HER2.[262]Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol. 2018 Jan;19(1):27-39.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30777-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29242041?tool=bestpractice.com
[267]Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72.
http://www.ncbi.nlm.nih.gov/pubmed/24529560?tool=bestpractice.com
[268]Liedtke C, Mazouni C, Hess KR, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008 Mar 10;26(8):1275-81.
https://ascopubs.org/doi/full/10.1200/JCO.2007.14.4147
http://www.ncbi.nlm.nih.gov/pubmed/18250347?tool=bestpractice.com
[269]von Minckwitz G, Untch M, Blohmer JU, et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol. 2012 May 20;30(15):1796-804.
https://ascopubs.org/doi/full/10.1200/JCO.2011.38.8595
http://www.ncbi.nlm.nih.gov/pubmed/22508812?tool=bestpractice.com
[270]Schettini F, Pascual T, Conte B, et al. HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: a systematic review and meta-analysis. Cancer Treat Rev. 2020 Mar;84:101965.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230134
http://www.ncbi.nlm.nih.gov/pubmed/32000054?tool=bestpractice.com
A resposta do tumor deve ser avaliada rotineiramente por exame clínico e de imagem (por exemplo, mamografia, ultrassonografia e/ou RNM) durante a terapia neoadjuvante.[147]Expert Panel on Breast Imaging, Hayward JH, Linden OE, et al. ACR Appropriateness Criteria® monitoring response to neoadjuvant systemic therapy for breast cancer: 2022 Update. J Am Coll Radiol. 2023 May;20(5s):S125-45.
https://acsearch.acr.org/docs/3099208/Narrative
http://www.ncbi.nlm.nih.gov/pubmed/37236739?tool=bestpractice.com
Se houver ausência de resposta ou progressão for observada, um esquema neoadjuvante alternativo e/ou radiação pré-operatória pode ser considerado. Se houver progressão e o câncer de mama for operável, a paciente deve ser encaminhada para cirurgia imediatamente.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Esquemas de quimioterapia
Geralmente incluem uma antraciclina e um taxano, com duração da terapia de, aproximadamente, 4.5 a 5 meses. Na maioria dos casos, assumindo resposta clínica à quimioterapia e tolerabilidade aceitável, os pacientes receberão toda a quimioterapia no cenário neoadjuvante.
Os esquemas recomendados incluem:[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Outros esquemas que podem ser considerados incluem:
Doxorrubicina associada a ciclofosfamida (AC)
Doxorrubicina associada a ciclofosfamida (AC) seguida de docetaxel ou paclitaxel
Epirrubicina associada a ciclofosfamida (EC)
Ciclofosfamida associada a metotrexato e fluoruracila (CMF)
Docetaxel associado a doxorrubicina e ciclofosfamida (TAC)
Docetaxel associado a carboplatina (em pacientes positivas para HER2, combinado com trastuzumabe com ou sem pertuzumabe).
Para pacientes selecionadas com doença triplo negativa, paclitaxel associado a carboplatina ou docetaxel associado a carboplatina pode ser considerado no pré-operatório. No entanto, agentes à base de platina não são recomendados como terapia adjuvante ou rotineiramente recomendados como terapia neoadjuvante para câncer de mama triplo negativo.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Os esquemas à base de antraciclinas (por exemplo, doxorrubicina, epirrubicina) com um taxano (por exemplo, docetaxel, paclitaxel), administrados concomitantemente ou sequencialmente, demonstraram reduzir o risco de recidiva e melhorar a sobrevida livre de doença e a sobrevida global, comparados aos esquemas à base de antraciclinas sem um taxano, e comparados com esquemas não baseados em antraciclinas.[271]Mamounas EP, Bryant J, Lembersky B, et al. Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: results from NSABP B-28. J Clin Oncol. 2005 Jun 1;23(16):3686-96.
https://ascopubs.org/doi/full/10.1200/JCO.2005.10.517
http://www.ncbi.nlm.nih.gov/pubmed/15897552?tool=bestpractice.com
[272]Henderson IC, Berry DA, Demetri GD, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003 Mar 15;21(6):976-83.
http://www.ncbi.nlm.nih.gov/pubmed/12637460?tool=bestpractice.com
[273]Gianni L, Baselga J, Eiermann W, et al. Phase III trial evaluating the addition of paclitaxel to doxorubicin followed by cyclophosphamide, methotrexate, and fluorouracil, as adjuvant or primary systemic therapy: European Cooperative Trial in Operable Breast Cancer. J Clin Oncol. 2009 May 20;27(15):2474-81.
http://www.ncbi.nlm.nih.gov/pubmed/19332727?tool=bestpractice.com
[274]De Laurentiis M, Cancello G, D'Agostino D, et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008 Jan 1;26(1):44-53.
https://ascopubs.org/doi/full/10.1200/JCO.2007.11.3787
http://www.ncbi.nlm.nih.gov/pubmed/18165639?tool=bestpractice.com
[275]Francis P, Crown J, Di Leo A, et al. Adjuvant chemotherapy with sequential or concurrent anthracycline and docetaxel: Breast International Group 02-98 randomized trial. J Natl Cancer Inst. 2008 Jan 16;100(2):121-33.
https://academic.oup.com/jnci/article/100/2/121/1130035
http://www.ncbi.nlm.nih.gov/pubmed/18182617?tool=bestpractice.com
[276]Martín M, Rodríguez-Lescure A, Ruiz A, et al. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by paclitaxel for early breast cancer. J Natl Cancer Inst. 2008 Jun 4;100(11):805-14.
https://academic.oup.com/jnci/article/100/11/805/896453
http://www.ncbi.nlm.nih.gov/pubmed/18505968?tool=bestpractice.com
[277]Shao N, Wang S, Yao C, et al. Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: a meta-analysis of phase III randomized control trials. Breast. 2012 Jun;21(3):389-93.
http://www.ncbi.nlm.nih.gov/pubmed/22542064?tool=bestpractice.com
[278]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71.
https://www.nejm.org/doi/full/10.1056/NEJMoa0707056
http://www.ncbi.nlm.nih.gov/pubmed/18420499?tool=bestpractice.com
[279]Qin YY, Li H, Guo XJ, et al. Adjuvant chemotherapy, with or without taxanes, in early or operable breast cancer: a meta-analysis of 19 randomized trials with 30698 patients. PLoS One. 2011 Nov 1;6(11):e26946.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0026946
http://www.ncbi.nlm.nih.gov/pubmed/22069477?tool=bestpractice.com
[280]Peto R, Davies C, Godwin J, et al; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Comparisons between different polychemotherapy regimens for early breast cancer: meta-analyses of long-term outcome among 100,000 women in 123 randomised trials. Lancet. 2012 Feb 4;379(9814):432-44.
http://www.ncbi.nlm.nih.gov/pubmed/22152853?tool=bestpractice.com
[281]Blum JL, Flynn PJ, Yothers G, et al. Anthracyclines in early breast cancer: the ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017 Aug 10;35(23):2647-55.
https://ascopubs.org/doi/10.1200/JCO.2016.71.4147
http://www.ncbi.nlm.nih.gov/pubmed/28398846?tool=bestpractice.com
[282]Willson ML, Burke L, Ferguson T, et al. Taxanes for adjuvant treatment of early breast cancer. Cochrane Database Syst Rev. 2019 Sep 2;(9):CD004421.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004421.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/31476253?tool=bestpractice.com
[
]
What are the effects of taxanes as adjuvant treatment for women with early breast cancer?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2783/fullMostre-me a resposta No entanto, as antraciclinas incorrem no risco de cardiotoxicidade, que deve ser avaliado em relação ao benefício. O momento ideal de se administrar um taxano com um esquema baseado em antraciclina (isto é, de maneira concomitante ou sequencial) não está claro, mas o risco de toxicidade é menor se administrado de maneira sequencial.[277]Shao N, Wang S, Yao C, et al. Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: a meta-analysis of phase III randomized control trials. Breast. 2012 Jun;21(3):389-93.
http://www.ncbi.nlm.nih.gov/pubmed/22542064?tool=bestpractice.com
[278]Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med. 2008 Apr 17;358(16):1663-71.
https://www.nejm.org/doi/full/10.1056/NEJMoa0707056
http://www.ncbi.nlm.nih.gov/pubmed/18420499?tool=bestpractice.com
[283]Eiermann W, Pienkowski T, Crown J, et al. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84.
https://ascopubs.org/doi/full/10.1200/JCO.2010.28.5437
http://www.ncbi.nlm.nih.gov/pubmed/21911726?tool=bestpractice.com
[284]Swain SM, Jeong JH, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65.
https://www.nejm.org/doi/full/10.1056/NEJMoa0909638
http://www.ncbi.nlm.nih.gov/pubmed/20519679?tool=bestpractice.com
[285]Zaheed M, Wilcken N, Willson ML, et al. Sequencing of anthracyclines and taxanes in neoadjuvant and adjuvant therapy for early breast cancer. Cochrane Database Syst Rev. 2019 Feb 18;(2):CD012873.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012873.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/30776132?tool=bestpractice.com
A quimioterapia sequencial de AC associado a paclitaxel pode aumentar a incidência de amenorreia, a qual demonstrou melhorar os desfechos para as mulheres na pré-menopausa com doença positiva para HR.[284]Swain SM, Jeong JH, Geyer CE Jr, et al. Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer. N Engl J Med. 2010 Jun 3;362(22):2053-65.
https://www.nejm.org/doi/full/10.1056/NEJMoa0909638
http://www.ncbi.nlm.nih.gov/pubmed/20519679?tool=bestpractice.com
Os esquemas de quimioterapia densos em doses demonstraram reduzir o risco de recorrência no câncer de mama em estádio inicial com linfonodo positivo, com uma sobrevida livre de doença a 4 anos de 82% para os esquemas densos em dose e 75% para outros.[286]Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9.
http://www.ncbi.nlm.nih.gov/pubmed/12668651?tool=bestpractice.com
Os esquemas não baseados em antraciclina (por exemplo, TC e CMF) são menos preferenciais, mas podem oferecer algumas vantagens sobre os esquemas baseados em antraciclina (por exemplo, menor risco de toxicidade, citopenias e leucemia).[287]Goldhirsch A, Colleoni M, Coates AS, et al; International Breast Cancer Study Group (IBCSG). Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? Ann Oncol. 1998 May;9(5):489-93.
https://www.annalsofoncology.org/article/S0923-7534(19)61004-5/pdf
http://www.ncbi.nlm.nih.gov/pubmed/9653488?tool=bestpractice.com
[288]Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7.
https://ascopubs.org/doi/full/10.1200/JCO.2006.06.5391
http://www.ncbi.nlm.nih.gov/pubmed/17135639?tool=bestpractice.com
[289]Jones S, Holmes FA, O'Shaughnessy J, et al. Docetaxel with cyclophosphamide Is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83.
http://www.ncbi.nlm.nih.gov/pubmed/19204201?tool=bestpractice.com
Foi relatada uma melhora nas sobrevidas global e livre de doença com 4 ciclos de TC, em comparação com AC (sem um taxano) no cenário adjuvante.[288]Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol. 2006 Dec 1;24(34):5381-7.
https://ascopubs.org/doi/full/10.1200/JCO.2006.06.5391
http://www.ncbi.nlm.nih.gov/pubmed/17135639?tool=bestpractice.com
[289]Jones S, Holmes FA, O'Shaughnessy J, et al. Docetaxel with cyclophosphamide Is associated with an overall survival benefit compared with doxorubicin and cyclophosphamide: 7-year follow-up of US Oncology Research Trial 9735. J Clin Oncol. 2009 Mar 10;27(8):1177-83.
http://www.ncbi.nlm.nih.gov/pubmed/19204201?tool=bestpractice.com
[290]Ding W, Li Z, Wang C, et al. Anthracycline versus nonanthracycline adjuvant therapy for early breast cancer: a systematic review and meta-analysis. Medicine (Baltimore). 2018 Oct;97(42):e12908.
https://journals.lww.com/md-journal/Fulltext/2018/10190/Anthracycline_versus_nonanthracycline_adjuvant.84.aspx
http://www.ncbi.nlm.nih.gov/pubmed/30335021?tool=bestpractice.com
No entanto, esses esquemas curtos de dois medicamentos (4 ciclos) são considerados menos efetivos que o esquema sequencial de AC associado a paclitaxel ou o esquema concomitante de três medicamentos, TAC. O CMF pode ser usado concomitantemente com a radioterapia.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[291]Isaac N, Panzarella T, Lau A, et al. Concurrent cyclophosphamide, methotrexate, and 5-fluorouracil chemotherapy and radiotherapy for breast carcinoma: a well tolerated adjuvant regimen. Cancer. 2002 Aug 15;95(4):696-703.
https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.10744
http://www.ncbi.nlm.nih.gov/pubmed/12209711?tool=bestpractice.com
Terapia neoadjuvante direcionada ao HER2
A terapia neoadjuvante para pacientes com câncer de mama positivo para HER2 deve incluir trastuzumabe e também pode incluir pertuzumabe (bloqueio duplo do HER2), combinada com quimioterapia neoadjuvante.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[167]Sparano JA, Gray RJ, Makower DF, et al. Clinical outcomes in early breast cancer with a high 21-gene recurrence score of 26 to 100 assigned to adjuvant chemotherapy plus endocrine therapy: a secondary analysis of the TAILORx randomized clinical trial. JAMA Oncol. 2019 Sep 30;6(3):367-74.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2752332
http://www.ncbi.nlm.nih.gov/pubmed/31566680?tool=bestpractice.com
[292]Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84.
http://www.ncbi.nlm.nih.gov/pubmed/20113825?tool=bestpractice.com
Os esquemas recomendados incluem: docetaxel associado a carboplatina associado a trastuzumabe associado a pertuzumabe (TCHP); ou docetaxel associado a carboplatina associado a trastuzumabe (TCH).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Os outros esquemas que podem ser considerados incluem: docetaxel associado a ciclofosfamida e trastuzumabe; doxorrubicina associado a ciclofosfamida (AC), seguidos por docetaxel ou paclitaxel associado a trastuzumabe, com ou sem pertuzumabe; ou paclitaxel associado a trastuzumabe e pertuzumabe.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Caso um esquema de quimioterapia baseado em antraciclina (por exemplo, AC associado a paclitaxel) esteja sendo usado, o trastuzumabe (com ou sem pertuzumabe) deve ser administrado após a antraciclina (por exemplo, junto com um taxano se o AC associado a paclitaxel for usado) para evitar aumentar o risco de cardiotoxicidade.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Os taxanos alternativos (por exemplo, paclitaxel, nanopartícula de paclitaxel ligada a albumina) podem ser substituídos, se necessário (por exemplo, se o paciente apresentar reação de hipersensibilidade).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
O trastuzumabe combinado com quimioterapia neoadjuvante demonstrou melhorar a sobrevida livre de eventos (razão de riscos [RR] 0.59, IC de 95% 0.38 a 0.90) e a taxa de resposta comparada com a quimioterapia neoadjuvante isolada nas pacientes com câncer de mama localmente avançado positivo para HER2.[292]Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84.
http://www.ncbi.nlm.nih.gov/pubmed/20113825?tool=bestpractice.com
O bloqueio duplo do HER2 combinado com a quimioterapia neoadjuvante melhora as taxas de resposta comparado com: bloqueio único do HER2 (com trastuzumabe) combinado com quimioterapia neoadjuvante; e trastuzumabe-entansina (um anticorpo monoclonal contra HER2 e inibidor de microtúbulos conjugado) associado a pertuzumabe sem quimioterapia neoadjuvante.[293]Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
http://www.ncbi.nlm.nih.gov/pubmed/22153890?tool=bestpractice.com
[294]Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84.
https://www.annalsofoncology.org/article/S0923-7534(19)36929-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23704196?tool=bestpractice.com
[295]Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800.
http://www.ncbi.nlm.nih.gov/pubmed/27179402?tool=bestpractice.com
[296]Swain SM, Ewer MS, Viale G, et al; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-53.
https://www.annalsofoncology.org/article/S0923-7534(19)35495-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29253081?tool=bestpractice.com
[297]Schneeweiss A, Chia S, Hickish T, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35.
http://www.ncbi.nlm.nih.gov/pubmed/29223479?tool=bestpractice.com
[298]Hurvitz SA, Martin M, Symmans WF, et al. Neoadjuvant trastuzumab, pertuzumab, and chemotherapy versus trastuzumab emtansine plus pertuzumab in patients with HER2-positive breast cancer (KRISTINE): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2018 Jan;19(1):115-26.
http://www.ncbi.nlm.nih.gov/pubmed/29175149?tool=bestpractice.com
[299]Hurvitz SA, Martin M, Jung KH, et al. Neoadjuvant trastuzumab emtansine and pertuzumab in human epidermal growth factor receptor 2-positive breast cancer: three-year outcomes from the phase III KRISTINE study. J Clin Oncol. 2019 Sep 1;37(25):2206-16.
https://ascopubs.org/doi/10.1200/JCO.19.00882
http://www.ncbi.nlm.nih.gov/pubmed/31157583?tool=bestpractice.com
[300]Shao Z, Pang D, Yang H, et al. Efficacy, safety, and tolerability of pertuzumab, trastuzumab, and docetaxel for patients with early or locally advanced ERBB2-positive breast cancer in Asia: the PEONY phase 3 randomized clinical trial. JAMA Oncol. 2020 Mar 1;6(3):e193692.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2753172
http://www.ncbi.nlm.nih.gov/pubmed/31647503?tool=bestpractice.com
[301]Chen S, Liang Y, Feng Z, et al. Efficacy and safety of HER2 inhibitors in combination with or without pertuzumab for HER2-positive breast cancer: a systematic review and meta-analysis. BMC Cancer. 2019 Oct 21;19(1):973.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6132-0
http://www.ncbi.nlm.nih.gov/pubmed/31638935?tool=bestpractice.com
O risco de efeitos adversos cardiovasculares (por exemplo, disfunção sistólica ventricular esquerda sintomática) não parece ser maior com bloqueio duplo do HER2, comparado com o trastuzumabe isoladamente (isto é, bloqueio único do HER2), mesmo quando usado com um esquema de quimioterapia baseado em antraciclina.[294]Schneeweiss A, Chia S, Hickish T, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013 Sep;24(9):2278-84.
https://www.annalsofoncology.org/article/S0923-7534(19)36929-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23704196?tool=bestpractice.com
[296]Swain SM, Ewer MS, Viale G, et al; BERENICE Study Group. Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Ann Oncol. 2018 Mar 1;29(3):646-53.
https://www.annalsofoncology.org/article/S0923-7534(19)35495-X/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29253081?tool=bestpractice.com
[297]Schneeweiss A, Chia S, Hickish T, et al. Long-term efficacy analysis of the randomised, phase II TRYPHAENA cardiac safety study: Evaluating pertuzumab and trastuzumab plus standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer. Eur J Cancer. 2018 Jan;89:27-35.
http://www.ncbi.nlm.nih.gov/pubmed/29223479?tool=bestpractice.com
Resultados de um estudo de fase 3 sugerem que o bloqueio duplo do HER2 pode evitar o uso de antraciclina no cenário neoadjuvante.[302]van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-40.
http://www.ncbi.nlm.nih.gov/pubmed/30413379?tool=bestpractice.com
A resposta patológica completa foi similar para pacientes que receberam quimioterapia neoadjuvante com ou sem antraciclinas na presença de bloqueio duplo do HER2, mas o uso de antraciclinas foi associado ao aumento do risco de neutropenia febril.[302]van Ramshorst MS, van der Voort A, van Werkhoven ED, et al. Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2018 Dec;19(12):1630-40.
http://www.ncbi.nlm.nih.gov/pubmed/30413379?tool=bestpractice.com
Essa abordagem requer investigações adicionais.
Uma formulação de dose fixa de trastuzumabe para uso subcutâneo (trastuzumabe/hialuronidase) não é inferior a trastuzumabe intravenoso e foi aprovada pela Food and Drug Administration (FDA) dos EUA para uso no câncer de mama com superexpressão de HER2.[303]Jackisch C, Hegg R, Stroyakovskiy D, et al. HannaH phase III randomised study: association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up. Eur J Cancer. 2016 Jul;62:62-75.
https://www.ejcancer.com/article/S0959-8049(16)32049-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27208905?tool=bestpractice.com
A FDA também aprovou uma combinação subcutânea de dose fixa de trastuzumabe/pertuzumabe/hialuronidase.
Após uma resposta patológica completa, o trastuzumabe e o pertuzumabe devem ser continuados no cenário adjuvante para completar 1 ano de tratamento.[292]Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010 Jan 30;375(9712):377-84.
http://www.ncbi.nlm.nih.gov/pubmed/20113825?tool=bestpractice.com
[295]Gianni L, Pienkowski T, Im YH, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016 Jun;17(6):791-800.
http://www.ncbi.nlm.nih.gov/pubmed/27179402?tool=bestpractice.com
[304]Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-205.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465633
http://www.ncbi.nlm.nih.gov/pubmed/28215665?tool=bestpractice.com
[305]Pivot X, Romieu G, Debled M, et al. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 2019 Jun 29;393(10191):2591-8.
http://www.ncbi.nlm.nih.gov/pubmed/31178155?tool=bestpractice.com
Para pacientes com doença residual após o bloqueio duplo do HER2 neoadjuvante, o trastuzumabe-entansina pode ser usado para tratamento adjuvante.[306]von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019 Feb 14;380(7):617-28.
https://www.nejm.org/doi/full/10.1056/NEJMoa1814017
http://www.ncbi.nlm.nih.gov/pubmed/30516102?tool=bestpractice.com
Terapia endócrina neoadjuvante
A terapia endócrina neoadjuvante isolada pode ser considerada para as mulheres no pós-menopausa com doença positiva para HR, negativa para HER2. Ela pode ser particularmente útil se a quimioterapia não for adequada (por exemplo, devido a idade e/ou comorbidades) ou nas mulheres com doença de baixo risco.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[261]Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 2021 May 1;39(13):1485-505.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274745
http://www.ncbi.nlm.nih.gov/pubmed/33507815?tool=bestpractice.com
[307]Morgan J, Wyld L, Collins KA. Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus). Cochrane Database Syst Rev. 2014 May 16;(5):CD004272.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004272.pub3/full
[308]Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-86.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2531471
http://www.ncbi.nlm.nih.gov/pubmed/27367583?tool=bestpractice.com
[Evidência C]6a1b7f95-ff68-4266-a21e-a0a1d1b4ab05guidelineCQuais são os efeitos da terapia endócrina neoadjuvante para mulheres menopausadas com câncer de mama localmente avançado em estádio inicial?[309]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jul 2018 [internet publication].
https://www.nice.org.uk/guidance/ng101
Nessas pacientes, o uso de inibidores da aromatase (por exemplo, exemestano, letrozol ou anastrozol) é preferível ao tamoxifeno.[261]Korde LA, Somerfield MR, Carey LA, et al. Neoadjuvant chemotherapy, endocrine therapy, and targeted therapy for breast cancer: ASCO guideline. J Clin Oncol. 2021 May 1;39(13):1485-505.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274745
http://www.ncbi.nlm.nih.gov/pubmed/33507815?tool=bestpractice.com
[308]Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-86.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2531471
http://www.ncbi.nlm.nih.gov/pubmed/27367583?tool=bestpractice.com
Relatou-se que a taxa de resposta e a taxa de conservação da mama são maiores com os inibidores da aromatase, comparados ao tamoxifeno no cenário neoadjuvante.[308]Spring LM, Gupta A, Reynolds KL, et al. Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer: a systematic review and meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-86.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2531471
http://www.ncbi.nlm.nih.gov/pubmed/27367583?tool=bestpractice.com
Pembrolizumabe neoadjuvante
O pembrolizumabe pode ser considerado para as pacientes com câncer de mama triplo negativo de estádio inicial T1cN1-2 ou T2-4N0 (estádio II ou III), em combinação com quimioterapia neoadjuvante, seguida por pembrolizumabe adjuvante após a cirurgia.[204]Korde LA, Somerfield MR, Hershman DL, et al. Use of immune checkpoint inhibitor pembrolizumab in the treatment of high-risk, early-stage triple-negative breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2022 May 20;40(15):1696-8.
https://ascopubs.org/doi/full/10.1200/JCO.22.00503
http://www.ncbi.nlm.nih.gov/pubmed/35417251?tool=bestpractice.com
Entre as pacientes com câncer de mama triplo negativo inicial, a porcentagem com resposta patológica completa foi significativamente maior entre aquelas que receberam o pembrolizumabe associado a quimioterapia neoadjuvante do que entre aquelas que receberam placebo associado a quimioterapia neoadjuvante.[205]Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020 Feb 27;382(9):810-21.
https://www.nejm.org/doi/10.1056/NEJMoa1910549
http://www.ncbi.nlm.nih.gov/pubmed/32101663?tool=bestpractice.com
Quimioterapia adjuvante
Pacientes com câncer de mama em estádio inicial com tumores >1.0 cm e que, provavelmente, se beneficiariam da quimioterapia costumam ser tratadas com quimioterapia adjuvante para reduzir o risco de recorrência.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A quimioterapia adjuvante pode ser considerada para as pacientes com tumores >0.5 cm a 1.0 cm no maior diâmetro se o tumor for triplo negativo ou positivo para HER2.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Geralmente, a quimioterapia adjuvante não é recomendada para pessoas com tumores ≤0.5 cm, embora possa ser considerada para aquelas com doença positiva para HER2.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Os esquemas de quimioterapia usados no cenário adjuvante são os mesmos daqueles usados no cenário neoadjuvante, e as mesmas considerações se aplicam em relação ao sequenciamento e à toxicidade.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[283]Eiermann W, Pienkowski T, Crown J, et al. Phase III study of doxorubicin/cyclophosphamide with concomitant versus sequential docetaxel as adjuvant treatment in patients with human epidermal growth factor receptor 2-normal, node-positive breast cancer: BCIRG-005 trial. J Clin Oncol. 2011 Oct 10;29(29):3877-84.
https://ascopubs.org/doi/full/10.1200/JCO.2010.28.5437
http://www.ncbi.nlm.nih.gov/pubmed/21911726?tool=bestpractice.com
[286]Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003 Apr 15;21(8):1431-9.
http://www.ncbi.nlm.nih.gov/pubmed/12668651?tool=bestpractice.com
[287]Goldhirsch A, Colleoni M, Coates AS, et al; International Breast Cancer Study Group (IBCSG). Adding adjuvant CMF chemotherapy to either radiotherapy or tamoxifen: are all CMFs alike? Ann Oncol. 1998 May;9(5):489-93.
https://www.annalsofoncology.org/article/S0923-7534(19)61004-5/pdf
http://www.ncbi.nlm.nih.gov/pubmed/9653488?tool=bestpractice.com
[310]Piccart MJ, Di Leo A, Beauduin M, et al. Phase III trial comparing two dose levels of epirubicin combined with cyclophosphamide with cyclophosphamide, methotrexate, and fluorouracil in node-positive breast cancer. J Clin Oncol. 2001 Jun 15;19(12):3103-10.
http://www.ncbi.nlm.nih.gov/pubmed/11408507?tool=bestpractice.com
[311]Martin M, Pienkowski T, Mackey J, et al; Breast Cancer International Research Group 001 Investigators. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005 Jun 2;352(22):2302-13.
https://www.nejm.org/doi/full/10.1056/NEJMoa043681
http://www.ncbi.nlm.nih.gov/pubmed/15930421?tool=bestpractice.com
[312]Nitz U, Gluz O, Clemens M, et al. West German Study PlanB Trial: adjuvant four cycles of epirubicin and cyclophosphamide plus docetaxel versus six cycles of docetaxel and cyclophosphamide in HER2-negative early breast cancer. J Clin Oncol. 2019 Apr 1;37(10):799-808.
http://www.ncbi.nlm.nih.gov/pubmed/30785826?tool=bestpractice.com
Estudos indicam que algumas pacientes com câncer de mama em estádio inicial positivas para HR/negativas para HER2 obtêm um benefício consideravelmente menor com a quimioterapia adjuvante (supondo a terapia endócrina padrão) que aquelas negativas para HR ou positivas para HER2.[313]Berry DA, Cirrincione C, Henderson IC, et al. Estrogen-receptor status and outcomes of modern chemotherapy for patients with node-positive breast cancer. JAMA. 2006 Apr 12;295(14):1658-67.
https://jamanetwork.com/journals/jama/fullarticle/202666
http://www.ncbi.nlm.nih.gov/pubmed/16609087?tool=bestpractice.com
Portanto, as pacientes com câncer de mama em estádio inicial positivas para HR/negativas para HER2 que forem patologicamente negativas para linfonodos ou algumas que tiverem 1-3 linfonodos positivos devem passar por uma avaliação de risco adicional com um ensaio de expressão gênica para ajudar a orientar as decisões sobre o uso de quimioterapia adjuvante. O ensaio de 21 genes Oncotype Dx® é preferível porque é validado para predizer o benefício da quimioterapia. Outros ensaios (por exemplo, Breast Cancer Index, MammaPrint®, Prosigna®, EndoPredict®) podem ser considerados para ajudar a avaliar o risco de recorrência.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[159]Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015 Nov 19;373(21):2005-14.
https://www.nejm.org/doi/full/10.1056/NEJMoa1510764
http://www.ncbi.nlm.nih.gov/pubmed/26412349?tool=bestpractice.com
[160]Goncalves R, Bose R. Using multigene tests to select treatment for early-stage breast cancer. J Natl Compr Canc Netw. 2013 Feb 1;11(2):174-82.
https://www.jnccn.org/content/11/2/174.long
http://www.ncbi.nlm.nih.gov/pubmed/23411384?tool=bestpractice.com
[161]Harbeck N, Sotlar K, Wuerstlein R, et al. Molecular and protein markers for clinical decision making in breast cancer: today and tomorrow. Cancer Treat Rev. 2014 Apr;40(3):434-44.
http://www.ncbi.nlm.nih.gov/pubmed/24138841?tool=bestpractice.com
[162]Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med. 2019 Jun 20;380(25):2395-405.
https://www.nejm.org/doi/10.1056/NEJMoa1904819
http://www.ncbi.nlm.nih.gov/pubmed/31157962?tool=bestpractice.com
[163]Andre F, Ismaila N, Allison KH, et al. Biomarkers for adjuvant endocrine and chemotherapy in early-stage breast cancer: ASCO guideline update. J Clin Oncol. 2022 Jun 1;40(16):1816-37.
https://ascopubs.org/doi/10.1200/JCO.22.00069
http://www.ncbi.nlm.nih.gov/pubmed/35439025?tool=bestpractice.com
[164]National Institute for Health and Care Excellence. Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. Dec 2018 [internet publication]
https://www.nice.org.uk/guidance/dg34
[165]Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004 Dec 30;351(27):2817-26.
https://www.nejm.org/doi/full/10.1056/NEJMoa041588
http://www.ncbi.nlm.nih.gov/pubmed/15591335?tool=bestpractice.com
[314]Henry NL, Somerfield MR, Abramson VG, et al. Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer: update of the ASCO endorsement of the Cancer Care Ontario guideline. J Clin Oncol. 2019 Aug 1;37(22):1965-77.
https://ascopubs.org/doi/full/10.1200/JCO.19.00948
http://www.ncbi.nlm.nih.gov/pubmed/31206315?tool=bestpractice.com
Vários ensaios clínicos (MINDACT, TAILORx e Plan B) identificaram grupos de pacientes que podem evitar a quimioterapia adjuvante com segurança.[166]Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018 Jul 12;379(2):111-21.
https://www.nejm.org/doi/10.1056/NEJMoa1804710
http://www.ncbi.nlm.nih.gov/pubmed/29860917?tool=bestpractice.com
[315]Cardoso F, van't Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016 Aug 25;375(8):717-29.
https://www.nejm.org/doi/full/10.1056/NEJMoa1602253
http://www.ncbi.nlm.nih.gov/pubmed/27557300?tool=bestpractice.com
[316]Nitz U, Gluz O, Christgen M, et al. Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial. Breast Cancer Res Treat. 2017 Oct;165(3):573-83.
https://link.springer.com/article/10.1007/s10549-017-4358-6
http://www.ncbi.nlm.nih.gov/pubmed/28664507?tool=bestpractice.com
[317]Esserman LJ, Yau C, Thompson CK, et al. Use of molecular tools to identify patients with indolent breast cancers with ultralow risk over 2 decades. JAMA Oncol. 2017 Nov 1;3(11):1503-10.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2634502
http://www.ncbi.nlm.nih.gov/pubmed/28662222?tool=bestpractice.com
A capecitabina adjuvante pode ser usada nas pacientes com câncer de mama triplo negativo, com doença residual após a terapia neoadjuvante com taxanos, agentes alquilantes ou antraciclinas. A capecitabina também pode ser usada como terapia de manutenção após a quimioterapia adjuvante para a doença triplo negativa.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[318]Masuda N, Lee SJ, Ohtani S, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Engl J Med. 2017 Jun 1;376(22):2147-59.
https://www.nejm.org/doi/full/10.1056/NEJMoa1612645
http://www.ncbi.nlm.nih.gov/pubmed/28564564?tool=bestpractice.com
Análises retrospectivas sugerem que a quimioterapia com docetaxel está associada a uma sobrevida livre de doença e sobrevida global desfavoráveis em pacientes obesas e com sobrepeso, comparadas com pacientes magras. Isso pode refletir o maior volume de distribuição de medicamentos lipofílicos em pacientes obesas e com sobrepeso. Não houve diferença entre a sobrevida livre de doença e a sobrevida global em pacientes magras, com sobrepeso e obesas do grupo de quimioterapia sem docetaxel.[319]Desmedt C, Fornili M, Clatot F, et al. Differential benefit of adjuvant docetaxel-based chemotherapy in patients with early breast cancer according to baseline body mass index. J Clin Oncol. 2020 Sep 1;38(25):2883-91.
http://www.ncbi.nlm.nih.gov/pubmed/32614702?tool=bestpractice.com
A quimioterapia com doses intensas, em que os medicamentos são administrados em intervalos mais curtos ou de maneira sequencial na dose total (vem vez de concomitantemente em doses mais baixas), reduz o risco de recorrência de câncer de mama em 10 anos, a mortalidade por câncer de mama e a mortalidade por todas as causas.[320]Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials. Lancet. 2019 Apr 6;393(10179):1440-52.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)33137-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30739743?tool=bestpractice.com
Existem disparidades raciais na administração de quimioterapia para câncer de mama em estádio inicial. Uma revisão sistemática e uma metanálise relataram atrasos clinicamente relevantes no início da quimioterapia adjuvante em pacientes negras com câncer de mama, comparadas com pacientes brancas.[321]Green AK, Aviki EM, Matsoukas K, et al. Racial disparities in chemotherapy administration for early-stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2018 Nov;172(2):247-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6958704
http://www.ncbi.nlm.nih.gov/pubmed/30094552?tool=bestpractice.com
Terapia adjuvante direcionada para HER2
O trastuzumabe adjuvante (combinado com quimioterapia adjuvante) é recomendado para pacientes com câncer de mama em estádio inicial positivo para HER2 que sejam negativas para linfonodos com tumores >1 cm a ≤2 cm.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
[322]Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83.
https://www.nejm.org/doi/full/10.1056/NEJMoa0910383
http://www.ncbi.nlm.nih.gov/pubmed/21991949?tool=bestpractice.com
[323]Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52.
https://ascopubs.org/doi/10.1200/JCO.2014.55.5730
http://www.ncbi.nlm.nih.gov/pubmed/25332249?tool=bestpractice.com
[324]Shen Y, Fujii T, Ueno NT, et al. Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis. Breast Cancer Res Treat. 2019 Jan;173(1):1-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538294
http://www.ncbi.nlm.nih.gov/pubmed/30242579?tool=bestpractice.com
[325]Wilson FR, Coombes ME, Brezden-Masley C, et al. Herceptin® (trastuzumab) in HER2-positive early breast cancer: a systematic review and cumulative network meta-analysis. Syst Rev. 2018 Nov 14;7(1):191.
https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-018-0854-y
http://www.ncbi.nlm.nih.gov/pubmed/30428932?tool=bestpractice.com
O trastuzumabe adjuvante (combinado com quimioterapia adjuvante) pode ser considerado para pacientes com câncer de mama em estádio inicial positivo para HER2 que sejam negativas para linfonodos com tumores ≤1 cm.[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
O sequenciamento e o momento da terapia adjuvante direcionada para HER2 em conjunto com a quimioterapia no cenário adjuvante segue os mesmos princípios do cenário neoadjuvante. Caso um esquema de quimioterapia baseado em antraciclina (por exemplo, AC associado a paclitaxel) esteja sendo usado, o trastuzumabe deve ser administrado após a antraciclina (por exemplo, junto com um taxano se AC associado a paclitaxel for usado) para evitar aumentar o risco de cardiotoxicidade. O trastuzumabe pode ser administrado junto com os esquemas de quimioterapia não baseados em antraciclinas (por exemplo, docetaxel associado a carboplatina).[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
[322]Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83.
https://www.nejm.org/doi/full/10.1056/NEJMoa0910383
http://www.ncbi.nlm.nih.gov/pubmed/21991949?tool=bestpractice.com
[323]Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52.
https://ascopubs.org/doi/10.1200/JCO.2014.55.5730
http://www.ncbi.nlm.nih.gov/pubmed/25332249?tool=bestpractice.com
As taxas de sobrevida livre de doença e sobrevida global são similares quando trastuzumabe é acrescentado a um esquema baseado em antraciclina ou não, mas o risco de cardiotoxicidade e leucemia é menor quando acrescentado a um esquema não baseado em antraciclina.[322]Slamon D, Eiermann W, Robert N, et al. Adjuvant trastuzumab in HER2-positive breast cancer. N Engl J Med. 2011 Oct 6;365(14):1273-83.
https://www.nejm.org/doi/full/10.1056/NEJMoa0910383
http://www.ncbi.nlm.nih.gov/pubmed/21991949?tool=bestpractice.com
[324]Shen Y, Fujii T, Ueno NT, et al. Comparative efficacy of adjuvant trastuzumab-containing chemotherapies for patients with early HER2-positive primary breast cancer: a network meta-analysis. Breast Cancer Res Treat. 2019 Jan;173(1):1-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538294
http://www.ncbi.nlm.nih.gov/pubmed/30242579?tool=bestpractice.com
O trastuzumabe administrado concomitantemente com um taxano (por exemplo, paclitaxel, docetaxel) parece ser seguro e é mais eficaz que quando administrado sequencialmente.[323]Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014 Nov 20;32(33):3744-52.
https://ascopubs.org/doi/10.1200/JCO.2014.55.5730
http://www.ncbi.nlm.nih.gov/pubmed/25332249?tool=bestpractice.com
Pacientes com câncer de mama em estádio inicial positivo para HER2 de alto risco (por exemplo, positivo para linfonodos e/ou tumores >2 cm) podem ser consideradas para bloqueio duplo do HER2 com trastuzumabe e pertuzumabe (combinado com quimioterapia adjuvante). Ficou comprovado que o bloqueio duplo do HER2 melhora a taxa de resposta e a taxa de sobrevida livre de doença com toxicidade adicional mínima, comparado a trastuzumabe isolado.[293]Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012 Jan;13(1):25-32.
http://www.ncbi.nlm.nih.gov/pubmed/22153890?tool=bestpractice.com
[301]Chen S, Liang Y, Feng Z, et al. Efficacy and safety of HER2 inhibitors in combination with or without pertuzumab for HER2-positive breast cancer: a systematic review and meta-analysis. BMC Cancer. 2019 Oct 21;19(1):973.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-019-6132-0
http://www.ncbi.nlm.nih.gov/pubmed/31638935?tool=bestpractice.com
[326]von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017 Jul 13;377(2):122-31.
https://www.nejm.org/doi/full/10.1056/NEJMoa1703643
http://www.ncbi.nlm.nih.gov/pubmed/28581356?tool=bestpractice.com
Pacientes de alto risco podem ser consideradas para terapia direcionada ao HER2 estendida com neratinibe por 1 ano após o início da terapia adjuvante direcionada ao HER2 baseada em trastuzumabe.[327]Chan A, Delaloge S, Holmes FA, et al. Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016 Mar;17(3):367-77.
http://www.ncbi.nlm.nih.gov/pubmed/26874901?tool=bestpractice.com
[328]Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-700.
http://www.ncbi.nlm.nih.gov/pubmed/29146401?tool=bestpractice.com
Foi demonstrado que o neratinibe reduz consideravelmente a recidiva (taxa de sobrevida livre de doença invasiva em 5 anos de 90.2% versus 87.7% para o placebo), mas está associado a aumento do risco de diarreia.[328]Martin M, Holmes FA, Ejlertsen B, et al. Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1688-700.
http://www.ncbi.nlm.nih.gov/pubmed/29146401?tool=bestpractice.com
As pacientes com câncer de mama em estádio inicial positivas para HER2 e de baixo risco (por exemplo, negativo para linfonodos e tumores pequenos com <3 cm) podem ser consideradas para terapia adjuvante com trastuzumabe associado a paclitaxel (isto é, sem antraciclina), principalmente se a tolerabilidade à quimioterapia representar uma preocupação em decorrência da idade e/ou comorbidades.[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
[329]Tolaney S, Barry WT, Dang CT, et al. A phase II study of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). Cancer Res. 2013;73(suppl 24):abstract S1-04.
https://cancerres.aacrjournals.org/content/73/24_Supplement/S1-04
[330]Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med. 2015 Jan 8;372(2):134-41.
https://www.nejm.org/doi/full/10.1056/NEJMoa1406281
http://www.ncbi.nlm.nih.gov/pubmed/25564897?tool=bestpractice.com
[331]Tolaney SM, Guo H, Pernas S, et al. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-75.
https://ascopubs.org/doi/full/10.1200/JCO.19.00066
http://www.ncbi.nlm.nih.gov/pubmed/30939096?tool=bestpractice.com
Foi relatada uma taxa de sobrevida livre de doença em 7 anos de 93% com essa abordagem.[331]Tolaney SM, Guo H, Pernas S, et al. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol. 2019 Aug 1;37(22):1868-75.
https://ascopubs.org/doi/full/10.1200/JCO.19.00066
http://www.ncbi.nlm.nih.gov/pubmed/30939096?tool=bestpractice.com
A terapia direcionada ao HER2 deve ser mantida por 1 ano. Isso oferece benefícios otimizados no longo prazo, em comparação com a continuação do tratamento por um período mais curto (≤6 meses) ou mais longo (2 anos).[201]Denduluri N, Somerfield MR, Eisen A, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2)-negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016 Jul 10;34(20):2416-27.
https://ascopubs.org/doi/full/10.1200/JCO.2016.67.0182
http://www.ncbi.nlm.nih.gov/pubmed/27091714?tool=bestpractice.com
[304]Cameron D, Piccart-Gebhart MJ, Gelber RD, et al. 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 2017 Mar 25;389(10075):1195-205.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5465633
http://www.ncbi.nlm.nih.gov/pubmed/28215665?tool=bestpractice.com
[305]Pivot X, Romieu G, Debled M, et al. 6 months versus 12 months of adjuvant trastuzumab in early breast cancer (PHARE): final analysis of a multicentre, open-label, phase 3 randomised trial. Lancet. 2019 Jun 29;393(10191):2591-8.
http://www.ncbi.nlm.nih.gov/pubmed/31178155?tool=bestpractice.com
[332]Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al; Herceptin Adjuvant (HERA) Trial Study Team. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013 Sep 21;382(9897):1021-8.
http://www.ncbi.nlm.nih.gov/pubmed/23871490?tool=bestpractice.com
[333]Pivot X, Romieu G, Debled M, et al; PHARE trial investigators. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013 Jul;14(8):741-8.
http://www.ncbi.nlm.nih.gov/pubmed/23764181?tool=bestpractice.com
[334]Goldvaser H, Korzets Y, Shepshelovich D, et al. Deescalating adjuvant trastuzumab in HER2-positive early-stage breast cancer: a systemic review and meta-analysis. JNCI Cancer Spectr. 2019 May 11;3(2):pkz033.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6649709
http://www.ncbi.nlm.nih.gov/pubmed/31360906?tool=bestpractice.com
[335]Joensuu H, Fraser J, Wildiers H, et al. Effect of adjuvant trastuzumab for a duration of 9 weeks vs 1 year with concomitant chemotherapy for early human epidermal growth factor receptor 2-positive breast cancer: the SOLD randomized clinical trial. JAMA Oncol. 2018 Sep 1;4(9):1199-206.
https://jamanetwork.com/journals/jamaoncology/fullarticle/2682589
http://www.ncbi.nlm.nih.gov/pubmed/29852043?tool=bestpractice.com
[336]Chen L, Zhou W, Hu X, et al. Short-duration versus 1-year adjuvant trastuzumab in early HER2 positive breast cancer: a meta-analysis of randomized controlled trials. Cancer Treat Rev. 2019 May;75:12-9.
https://www.cancertreatmentreviews.com/article/S0305-7372(19)30040-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/30856373?tool=bestpractice.com
[337]Inno A, Barni S, Ghidini A, et al. One year versus a shorter duration of adjuvant trastuzumab for HER2-positive early breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019 Jan;173(2):247-54.
http://www.ncbi.nlm.nih.gov/pubmed/30317424?tool=bestpractice.com
Biossimilares de trastuzumabe foram aprovados para o tratamento do câncer de mama; eles oferecem eficácia similar, perfil de segurança similar e imunogenicidade equivalente ao produto original, sem o custo adicional.[338]Migliavacca Zucchetti B, Nicolò E, Curigliano G. Biosimilars for breast cancer. Expert Opin Biol Ther. 2019 Oct;19(10):1015-21.
http://www.ncbi.nlm.nih.gov/pubmed/31248290?tool=bestpractice.com
Uma formulação de dose fixa de trastuzumabe para uso subcutâneo (trastuzumabe/hialuronidase) não é inferior a trastuzumabe intravenoso e foi aprovada pela FDA para uso no câncer de mama com superexpressão de HER2.[303]Jackisch C, Hegg R, Stroyakovskiy D, et al. HannaH phase III randomised study: association of total pathological complete response with event-free survival in HER2-positive early breast cancer treated with neoadjuvant-adjuvant trastuzumab after 2 years of treatment-free follow-up. Eur J Cancer. 2016 Jul;62:62-75.
https://www.ejcancer.com/article/S0959-8049(16)32049-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/27208905?tool=bestpractice.com
A FDA também aprovou uma combinação subcutânea de dose fixa de trastuzumabe/pertuzumabe/hialuronidase.
Terapia adjuvante direcionada ao HER2 para doença residual
Trastuzumabe-entansina é um conjugado anticorpo-medicamento de trastuzumabe e um inibidor citotóxico microtubular. Pode ser usado para o tratamento adjuvante de pacientes positivas para HER2 com câncer de mama em estádio inicial que tenham doença residual invasiva no momento da cirurgia, após o tratamento neoadjuvante baseado em trastuzumabe.[306]von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019 Feb 14;380(7):617-28.
https://www.nejm.org/doi/full/10.1056/NEJMoa1814017
http://www.ncbi.nlm.nih.gov/pubmed/30516102?tool=bestpractice.com
[339]Denduluri N, Somerfield MR, Chavez-MacGregor M, et al. Selection of optimal adjuvant chemotherapy and targeted therapy for early breast cancer: ASCO guideline update. J Clin Oncol. 2021 Feb 20;39(6):685-93.
https://ascopubs.org/doi/10.1200/JCO.20.02510
http://www.ncbi.nlm.nih.gov/pubmed/33079579?tool=bestpractice.com
O trastuzumabe-entansina reduziu o risco de recorrência ou morte em aproximadamente 50%, comparado com o trastuzumabe isolado nessas pacientes.[306]von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019 Feb 14;380(7):617-28.
https://www.nejm.org/doi/full/10.1056/NEJMoa1814017
http://www.ncbi.nlm.nih.gov/pubmed/30516102?tool=bestpractice.com
Relatos de fadiga, trombocitopenia e neuropatia periférica foram maiores com trastuzumabe-entansina.[306]von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med. 2019 Feb 14;380(7):617-28.
https://www.nejm.org/doi/full/10.1056/NEJMoa1814017
http://www.ncbi.nlm.nih.gov/pubmed/30516102?tool=bestpractice.com
Terapia adjuvante para doença positiva para HR
A terapia endócrina é recomendada para a maioria das pacientes com câncer de mama positivo para HR (por exemplo, pacientes positivas para linfonodos ou negativas para linfonodos com tumores >0.5 cm), e geralmente é administrada no cenário adjuvante (ou seja, após a cirurgia e a quimioterapia, se aplicada).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
A terapia endócrina adjuvante pode ser considerada para pacientes negativas para linfonodos com tumores ≤0.5 cm (ou seja, baixo risco), com base em uma discussão com a paciente sobre os riscos e benefícios.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
O tipo de terapia endócrina usada no cenário adjuvante é determinado pelo estado menopáusico no diagnóstico.
Terapia endócrina adjuvante para mulheres na pré-menopausa com doença positiva para HR
Geralmente, as mulheres na pré-menopausa com doença positiva para HR são tratadas com tamoxifeno adjuvante (após a cirurgia e a quimioterapia, se administrada).[340]Albain KS, Barlow WE, Ravdin PM, et al. Adjuvant chemotherapy and timing of tamoxifen in postmenopausal patients with endocrine-responsive, node-positive breast cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Dec 19;374(9707):2055-63.
http://www.ncbi.nlm.nih.gov/pubmed/20004966?tool=bestpractice.com
[341]Alkner S, Bendahl PO, Ferno M, et al. Tamoxifen reduces the risk of contralateral breast cancer in premenopausal women: results from a controlled randomised trial. Eur J Cancer. 2009 Sep;45(14):2496-502.
http://www.ncbi.nlm.nih.gov/pubmed/19535242?tool=bestpractice.com
Para determinadas pacientes com alto risco de recorrência (por exemplo, mulheres jovens com tumor de alto grau e linfonodos positivos), o tamoxifeno ou um inibidor da aromatase pode ser administrado em combinação com a supressão ovariana (por exemplo, gosserrelina) ou ablação por ooforectomia cirúrgica.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[342]Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. 2022 Mar;23(3):382-92.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8885431
http://www.ncbi.nlm.nih.gov/pubmed/35123662?tool=bestpractice.com
Foi comprovado que a combinação de terapia endócrina adjuvante com supressão ou ablação ovariana melhora as taxas de sobrevida livre de doença e reduz a mortalidade em mulheres na pré-menopausa com doença positiva para HR.[343]Francis PA, Pagani O, Fleming GF, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018 Jul 12;379(2):122-37.
https://www.nejm.org/doi/full/10.1056/NEJMoa1803164
http://www.ncbi.nlm.nih.gov/pubmed/29863451?tool=bestpractice.com
[344]Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med. 2014 Jul 10;371(2):107-18.
https://www.nejm.org/doi/full/10.1056/NEJMoa1404037
http://www.ncbi.nlm.nih.gov/pubmed/24881463?tool=bestpractice.com
[345]Kim HA, Lee JW, Nam SJ, et al. Adding ovarian suppression to tamoxifen for premenopausal breast cancer: a randomized phase III trial. J Clin Oncol. 2020 Feb 10;38(5):434-43.
https://ascopubs.org/doi/10.1200/JCO.19.00126
http://www.ncbi.nlm.nih.gov/pubmed/31518174?tool=bestpractice.com
[346]Pagani O, Walley BA, Fleming GF, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer: long-term follow-up of the combined TEXT and SOFT trials. J Clin Oncol. 2023 Mar 1;41(7):1376-82.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10419413
http://www.ncbi.nlm.nih.gov/pubmed/36521078?tool=bestpractice.com
A decisão de usar a supressão ou ablação ovariana deve levar em consideração o tumor e as características da paciente, além dos efeitos adversos esperados, e basear-se em uma discussão dos riscos e benefícios do tratamento.[347]Bui KT, Willson ML, Goel S, et al. Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer. Cochrane Database Syst Rev. 2020 Mar 6;(3):CD013538.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013538/full
http://www.ncbi.nlm.nih.gov/pubmed/32141074?tool=bestpractice.com
A terapia endócrina é mantida por pelo menos 5 anos. Após 5 anos de tratamento com tamoxifeno, algumas pacientes de alto risco podem considerar a continuação do tratamento com tamoxifeno por mais 5 anos, trocar para um inibidor da aromatase por 5 anos (se menopausada) ou interromper o tratamento endócrino (se estiver na pré-menopausa).[348]Davies C, Pan H, Godwin J, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013 Mar 9;381(9869):805-16.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)61963-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/23219286?tool=bestpractice.com
[349]Gray RG, Rea D, Handley K, et al. aTTom: long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years in 6,953 women with early breast cancer. J Clin Oncol. 2013 Jun 20;31(18) suppl: abstr 5.
https://meetinglibrary.asco.org/record/83728/abstract
A toxicidade (incluindo a taxa de câncer de endométrio) pode ser maior com a extensão do tratamento com tamoxifeno.[350]Pan H, Gray R, Braybrooke J, et al. 20-year risks of breast-cancer recurrence after stopping endocrine therapy at 5 years. N Engl J Med. 2017 Nov 9;377(19):1836-46.
https://www.nejm.org/doi/full/10.1056/NEJMoa1701830
http://www.ncbi.nlm.nih.gov/pubmed/29117498?tool=bestpractice.com
Aquelas que tomam um inibidor da aromatase como terapia endócrina inicial podem considerar continuar o tratamento por mais 3 a 5 anos.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A supressão temporária da função ovariana com agonistas do hormônio liberador de gonadotrofina pode ser considerada durante a quimioterapia para preservar a função ovariana e a fertilidade em mulheres na pré-menopausa.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Uma metanálise relatou uma taxa mais alta de gravidez em mulheres que receberam supressão ovariana temporária durante a quimioterapia, comparadas com mulheres do grupo de controle. Não houve diferença significativa na sobrevida livre de doença ou na sobrevida global entre os grupos.[351]Lambertini M, Moore HCF, Leonard RCF, et al. Gonadotropin-releasing hormone agonists during chemotherapy for preservation of ovarian function and fertility in premenopausal patients with early breast cancer: a systematic review and meta-analysis of individual patient-level data. J Clin Oncol. 2018 Jul 1;36(19):1981-90.
https://ascopubs.org/doi/10.1200/JCO.2018.78.0858
http://www.ncbi.nlm.nih.gov/pubmed/29718793?tool=bestpractice.com
Terapia endócrina adjuvante para mulheres menopausadas com doença positiva para HR
A terapia endócrina é recomendada para a maioria das pacientes com câncer de mama positivo para HR (por exemplo, pacientes positivas para linfonodos ou negativas para linfonodos com tumores >0.5 cm), e geralmente é administrada no cenário adjuvante (ou seja, após a cirurgia e a quimioterapia, se aplicada).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
A terapia endócrina adjuvante pode ser considerada para pacientes negativas para linfonodos com tumores ≤0.5 cm (ou seja, baixo risco), com base em uma discussão com a paciente sobre os riscos e benefícios.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
O tipo de terapia endócrina usada no cenário adjuvante é determinado pelo estado menopáusico no diagnóstico.
As mulheres menopausadas com doença positiva para HR, geralmente são tratadas com terapia adjuvante com inibidor da aromatase, que é mantida por 5 anos. De forma alternativa, um inibidor da aromatase pode ser administrado após 2 ou 3 anos de tamoxifeno (para completar 5 anos de terapia endócrina).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
Ficou comprovado que os inibidores da aromatase adjuvantes melhoram a sobrevida livre de doença em 18% para 21%, comparados a tamoxifeno adjuvante.[352]Coates AS, Keshaviah A, Thürlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007 Feb 10;25(5):486-92.
https://ascopubs.org/doi/full/10.1200/JCO.2006.08.8617
http://www.ncbi.nlm.nih.gov/pubmed/17200148?tool=bestpractice.com
[353]Howell A, Cuzick J, Baum M, et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005 Jan 1-7;365(9453):60-2.
http://www.ncbi.nlm.nih.gov/pubmed/15639680?tool=bestpractice.com
[354]Forbes JF, Cuzick J, Buzdar A, et al; Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trialists' Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008 Jan;9(1):45-53.
http://www.ncbi.nlm.nih.gov/pubmed/18083636?tool=bestpractice.com
[355]Joerger M, Thurlimann B. Update of the BIG 1-98 Trial: where do we stand? Breast. 22009 Oct;18 Suppl 3:S78-82.
http://www.ncbi.nlm.nih.gov/pubmed/19914548?tool=bestpractice.com
A maior eficácia dos inibidores da aromatase, comparada com a do tamoxifeno, é mantida em longo prazo.[356]Ruhstaller T, Giobbie-Hurder A, Colleoni M, et al. Adjuvant letrozole and tamoxifen alone or sequentially for postmenopausal women with hormone receptor-positive breast cancer: long-term follow-up of the BIG 1-98 trial. J Clin Oncol. 2019 Jan 10;37(2):105-14.
https://ascopubs.org/doi/10.1200/JCO.18.00440
http://www.ncbi.nlm.nih.gov/pubmed/30475668?tool=bestpractice.com
Mulheres menopausadas de alto risco com doença positiva para HR (por exemplo, linfonodo positivo) podem ser consideradas para terapia endócrina adjuvante prolongada por até 10 anos para reduzir o risco de recorrência.[357]Goss PE, Ingle JN, Pritchard KI, et al. Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med. 2016 Jul 21;375(3):209-19.
https://www.nejm.org/doi/full/10.1056/NEJMoa1604700
http://www.ncbi.nlm.nih.gov/pubmed/27264120?tool=bestpractice.com
[358]Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019 Feb 10;37(5):423-38.
https://ascopubs.org/doi/full/10.1200/JCO.18.01160
http://www.ncbi.nlm.nih.gov/pubmed/30452337?tool=bestpractice.com
[359]Mamounas EP, Bandos H, Lembersky BC, et al. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Jan;20(1):88-99.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6691732
http://www.ncbi.nlm.nih.gov/pubmed/30509771?tool=bestpractice.com
A duração ideal é desconhecida; esquemas prolongados reduzem o risco de recorrência, particularmente em cânceres em estágio avançado, mas o risco de efeitos adversos é maior.[358]Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019 Feb 10;37(5):423-38.
https://ascopubs.org/doi/full/10.1200/JCO.18.01160
http://www.ncbi.nlm.nih.gov/pubmed/30452337?tool=bestpractice.com
[360]Del Mastro L, Mansutti M, Bisagni G, et al. Extended therapy with letrozole as adjuvant treatment of postmenopausal patients with early-stage breast cancer: a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021 Oct;22(10):1458-67.
http://www.ncbi.nlm.nih.gov/pubmed/34543613?tool=bestpractice.com
[361]Gnant M, Fitzal F, Rinnerthaler G, et al. Duration of adjuvant aromatase-inhibitor therapy in postmenopausal breast cancer. N Engl J Med. 2021 Jul 29;385(5):395-405.
https://www.nejm.org/doi/10.1056/NEJMoa2104162
http://www.ncbi.nlm.nih.gov/pubmed/34320285?tool=bestpractice.com
O tamoxifeno pode ser considerado nas mulheres menopausadas por 5 anos (ou até 10 anos, se de alto risco) se os inibidores da aromatase forem recusados ou contraindicados.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Abemaciclibe e ribociclibe adjuvantes
Nas pacientes HR-positivas e HER2-negativas, o abemaciclibe ou o ribociclibe (inibidores da quinase 4 e 6 dependente de ciclina [CDK 4/6]), administrados em combinação com a terapia endócrina, levam a uma melhora significativa na sobrevida livre de doença invasiva em comparação com a terapia endócrina somente.[210]Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-98.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339
http://www.ncbi.nlm.nih.gov/pubmed/32954927?tool=bestpractice.com
[362]Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024 Mar 21;390(12):1080-91.
https://www.nejm.org/doi/10.1056/NEJMoa2305488
http://www.ncbi.nlm.nih.gov/pubmed/38507751?tool=bestpractice.com
Demonstrou-se que o benefício continua após a conclusão do tratamento com abemaciclibe (acompanhamento de 5 anos).[363]Rastogi P, O'Shaughnessy J, Martin M, et al. Adjuvant abemaciclib plus endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, high-risk early breast cancer: results from a preplanned monarchE overall survival interim analysis, including 5-year efficacy outcomes. J Clin Oncol. 2024 Mar 20;42(9):987-93.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10950161
http://www.ncbi.nlm.nih.gov/pubmed/38194616?tool=bestpractice.com
Tanto o abemaciclibe quanto o ribociclibe podem ser considerados para as pacientes com câncer de mama inicial HR-positivo e HER2-negativo com alto risco de recorrência.
O abemaciclibe pode ser considerado para as pacientes que tiverem ≥4 linfonodos axilares positivos ou 1-3 linfonodos axilares positivos e pelo menos um dos seguintes critérios: tamanho do tumor ≥5 cm ou grau histológico 3. O abemaciclibe é recomendado por 2 anos em combinação com a terapia endócrina (associado a supressão/ablação ovariana, se indicada).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[210]Johnston SRD, Harbeck N, Hegg R, et al. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-98.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768339
http://www.ncbi.nlm.nih.gov/pubmed/32954927?tool=bestpractice.com
[209]Freedman RA, Caswell-Jin JL, Hassett M, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-cyclin-dependent kinase 4 and 6 inhibitors: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2024 Jun 20;42(18):2233-5.
https://ascopubs.org/doi/10.1200/JCO.24.00886
http://www.ncbi.nlm.nih.gov/pubmed/38768407?tool=bestpractice.com
O ribociclibe pode ser considerado para pacientes com envolvimento de qualquer linfonodo, ou com tamanho do tumor >5 cm, ou com tumor de grau 2 ou grau 3 de tamanho 2-5 cm. O ribociclibe é recomendado por 3 anos em combinação com um inibidor da aromatase (além de supressão/ablação ovariana se pré-menopausa).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[362]Slamon D, Lipatov O, Nowecki Z, et al. Ribociclib plus endocrine therapy in early breast cancer. N Engl J Med. 2024 Mar 21;390(12):1080-91.
https://www.nejm.org/doi/10.1056/NEJMoa2305488
http://www.ncbi.nlm.nih.gov/pubmed/38507751?tool=bestpractice.com
[209]Freedman RA, Caswell-Jin JL, Hassett M, et al. Optimal adjuvant chemotherapy and targeted therapy for early breast cancer-cyclin-dependent kinase 4 and 6 inhibitors: ASCO Guideline Rapid Recommendation Update. J Clin Oncol. 2024 Jun 20;42(18):2233-5.
https://ascopubs.org/doi/10.1200/JCO.24.00886
http://www.ncbi.nlm.nih.gov/pubmed/38768407?tool=bestpractice.com
O tratamento com abemaciclibe ou ribociclibe é iniciado após a conclusão da cirurgia, radioterapia e/ou quimioterapia, simultaneamente à terapia endócrina (com ou sem supressão/ablação ovariana).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Olaparibe adjuvante
O olaparibe pode ser oferecido às pacientes com câncer de mama em estádio inicial positivas para HER2 com alto risco de recorrência e variantes patogênicas ou provavelmente patogênicas das linhas germinativas de BRCA1 ou BRCA2.[206]Tung NM, Zakalik D, Somerfield MR, et al. Adjuvant PARP inhibitors in patients with high-risk early-stage HER2-negative breast cancer and germline BRCA mutations: ASCO hereditary breast cancer guideline rapid recommendation update. J Clin Oncol. 2021 Sep 10;39(26):2959-61.
https://ascopubs.org/doi/full/10.1200/JCO.21.01532
http://www.ncbi.nlm.nih.gov/pubmed/34343058?tool=bestpractice.com
[207]Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021 Jun 24;384(25):2394-405.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9126186
http://www.ncbi.nlm.nih.gov/pubmed/34081848?tool=bestpractice.com
[208]Emens LA, Adams S, Cimino-Mathews A, et al. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer. J Immunother Cancer. 2021 Aug;9(8):e002597.
https://jitc.bmj.com/content/9/8/e002597.long
http://www.ncbi.nlm.nih.gov/pubmed/34389617?tool=bestpractice.com
Deve-se oferecer o olaparibe adjuvante por um período de um ano após a conclusão da quimioterapia neoadjuvante e do tratamento local, inclusive com radiação.
Nas pacientes elegíveis para olaparibe e abemaciclibe adjuvante, a sequência ideal das terapias é desconhecida.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Pembrolizumabe adjuvante
O pembrolizumabe pode ser considerado para as pacientes com câncer de mama triplo negativo de estádio inicial T1cN1-2 ou T2-4N0 (estádio II ou III), em combinação com quimioterapia neoadjuvante, seguida por pembrolizumabe adjuvante após a cirurgia.[204]Korde LA, Somerfield MR, Hershman DL, et al. Use of immune checkpoint inhibitor pembrolizumab in the treatment of high-risk, early-stage triple-negative breast cancer: ASCO guideline rapid recommendation update. J Clin Oncol. 2022 May 20;40(15):1696-8.
https://ascopubs.org/doi/full/10.1200/JCO.22.00503
http://www.ncbi.nlm.nih.gov/pubmed/35417251?tool=bestpractice.com
Esquema recomendado para doença triplo negativa de alto risco: pembrolizumabe associado a carboplatina e paclitaxel, seguidos por pembrolizumabe associado a ciclofosfamida e doxorrubicina ou epirrubicina, seguidos por pembrolizumabe adjuvante.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Radioterapia pós-lumpectomia
O planejamento e a administração da radiação devem ser individualizados. O planejamento do tratamento baseado na TC é preferível, e devem ser usadas técnicas para reduzir a exposição à radiação dos tecidos e órgãos normais.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A radioterapia de mama total é altamente recomendada para a maioria das pacientes após lumpectomia (e quimioterapia, se administrada), pois reduz o risco de recorrência local e mortalidade por câncer de mama.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[364]Darby S, McGale P, Correa C, et al; Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10801 women in 17 randomised trials. Lancet. 2011 Nov 12;378(9804):1707-16.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61629-2/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/22019144?tool=bestpractice.com
[365]Sedlmayer F, Sautter-Bihl ML, Budach W, et al. DEGRO practical guidelines: radiotherapy of breast cancer I: radiotherapy following breast conserving therapy for invasive breast cancer. Strahlenther Onkol. 2013 Oct;189(10):825-33.
https://link.springer.com/article/10.1007/s00066-013-0437-8
http://www.ncbi.nlm.nih.gov/pubmed/24002382?tool=bestpractice.com
[366]Korzets Y, Fyles A, Shepshelovich D, et al. Toxicity and clinical outcomes of partial breast irradiation compared to whole breast irradiation for early-stage breast cancer: a systematic review and meta-analysis. Breast Cancer Res Treat. 2019 Jun;175(3):531-45.
http://www.ncbi.nlm.nih.gov/pubmed/30929116?tool=bestpractice.com
[367]Vicini FA, Cecchini RS, White JR, et al. Long-term primary results of accelerated partial breast irradiation after breast-conserving surgery for early-stage breast cancer: a randomised, phase 3, equivalence trial. Lancet. 2019 Dec 14;394(10215):2155-64.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199428
http://www.ncbi.nlm.nih.gov/pubmed/31813636?tool=bestpractice.com
O reforço da radioterapia e da terapia de ILR pode reduzir ainda mais o risco de recorrência em pacientes com doença de alto risco.[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[368]Whelan TJ, Olivotto IA, Parulekar WR, et al. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015 Jul 23;373(4):307-16.
http://www.ncbi.nlm.nih.gov/pubmed/26200977?tool=bestpractice.com
[369]Whelan TJ, Olivotto IA, Levine MN. Regional nodal irradiation in early-stage breast cancer. N Engl J Med. 2015 Nov 5;373(19):1878-9.
http://www.ncbi.nlm.nih.gov/pubmed/26535517?tool=bestpractice.com
[370]Thorsen LB, Offersen BV, Danø H, et al. DBCG-IMN: A population-based cohort study on the effect of internal mammary node irradiation in early node-positive breast cancer. J Clin Oncol. 2016 Feb 1;34(4):314-20.
https://ascopubs.org/doi/full/10.1200/JCO.2015.63.6456
http://www.ncbi.nlm.nih.gov/pubmed/26598752?tool=bestpractice.com
[371]Kindts I, Laenen A, Depuydt T, et al. Tumour bed boost radiotherapy for women after breast-conserving surgery. Cochrane Database Syst Rev. 2017 Nov 6;(11):CD011987.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011987.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/29105051?tool=bestpractice.com
Para pacientes de baixo risco altamente selecionadas, IPAM/PAM pode ser uma opção alternativa à radioterapia de mama total, com o benefício de poupar tecido mamário saudável e reduzir o tempo de tratamento e alguns efeitos adversos relacionados ao tratamento (por exemplo, toxicidade aguda da pele).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[372]Haussmann J, Budach W, Corradini S, et al. Comparison of adverse events in partial- or whole breast radiotherapy: investigation of cosmesis, toxicities and quality of life in a meta-analysis of randomized trials. Radiat Oncol. 2023 Nov 2;18(1):181.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10623828
http://www.ncbi.nlm.nih.gov/pubmed/37919752?tool=bestpractice.com
[373]Shaitelman SF, Anderson BM, Arthur DW, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2024 Mar-Apr;14(2):112-32.
https://www.practicalradonc.org/article/S1879-8500(23)00296-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37977261?tool=bestpractice.com
A radioterapia é administrada após a conclusão da quimioterapia adjuvante (exceto capecitabina e olaparibe, que são administrados após a radioterapia, e CMF, que pode ser administrado simultaneamente).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A radioterapia pode ser administrada simultaneamente com trastuzumabe adjuvante em pacientes positivas para HER2.[374]Halyard MY, Pisansky TM, Dueck AC, et al. Radiotherapy and adjuvant trastuzumab in operable breast cancer: tolerability and adverse event data from the NCCTG Phase III Trial N9831. J Clin Oncol. 2009 Jun 1;27(16):2638-44.
http://www.ncbi.nlm.nih.gov/pubmed/19349549?tool=bestpractice.com
Pode-se considerar a omissão da radioterapia em pacientes idosas altamente selecionadas (por exemplo, com idade ≥65 anos, HR positivo, HER negativo, tumor de tamanho pequeno) que estejam planejando terapia endócrina.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
Radioterapia pós-lumpectomia: linfonodos axilares negativos
A radioterapia de mama total, com ou sem reforço no leito tumoral, é recomendada para a maioria das pacientes com linfonodos axilares negativos.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A ILR abrangente pode ser considerada juntamente com a radioterapia de mama total para pacientes com características de alto risco (por exemplo, tumores centrais/mediais; tamanho do tumor >5 cm; ou tamanho do tumor ≥2 cm associado a grau 3, ER negativo ou invasão linfovascular extensa).
Esquemas hipofracionados (com menos frações de dose mais altas em um período mais curto) são normalmente recomendados para radioterapia de mama total.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[375]Bentzen SM, Agrawal RK, Aird EG, et al; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008 Apr;9(4):331-41.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70077-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/18356109?tool=bestpractice.com
[376]Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013 Oct;14(11):1086-94.
https://www.doi.org/10.1016/S1470-2045(13)70386-3
http://www.ncbi.nlm.nih.gov/pubmed/24055415?tool=bestpractice.com
[377]Bentzen SM, Agrawal RK, Aird EG, et al; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60348-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/18355913?tool=bestpractice.com
[378]Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20.
https://www.nejm.org/doi/full/10.1056/NEJMoa0906260
http://www.ncbi.nlm.nih.gov/pubmed/20147717?tool=bestpractice.com
[379]Hickey BE, James ML, Lehman M, et al. Hypofractionated radiation therapy for early breast cancer. Cochrane Database Syst Rev. 2016 Jul 18;(7):CD003860.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003860.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/27425588?tool=bestpractice.com
[
]
In women with early breast cancer who have undergone breast conserving surgery, how does hypofractionation compare with conventional fractionation?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.1501/fullMostre-me a resposta A radioterapia hipofracionada reduz o risco de edema mamário, telangiectasia e toxicidade aguda da radiação na pele em comparação com esquemas convencionais.[380]Andrade TRM, Fonseca MCM, Segreto HRC, et al. Meta-analysis of long-term efficacy and safety of hypofractionated radiotherapy in the treatment of early breast cancer. Breast. 2019 Dec;48:24-31.
http://www.ncbi.nlm.nih.gov/pubmed/31476695?tool=bestpractice.com
Esquemas ultra-hipofracionados podem ser considerados para pacientes selecionadas com doença em estágio inicial, com linfonodos negativos, com idade >50 anos após cirurgia conservadora da mama (particularmente aquelas que não estão recebendo um reforço).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Esquemas ultra-hipofracionados mostraram resultados semelhantes quando comparados com esquemas hipofracionados.[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[381]Murray Brunt A, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020 May 23;395(10237):1613-26.
https://www.doi.org/10.1016/S0140-6736(20)30932-6
http://www.ncbi.nlm.nih.gov/pubmed/32580883?tool=bestpractice.com
[382]Brunt AM, Haviland JS, Sydenham M, et al. Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer. J Clin Oncol. 2020 Oct 1;38(28):3261-72.
https://www.doi.org/10.1200/JCO.19.02750
http://www.ncbi.nlm.nih.gov/pubmed/32663119?tool=bestpractice.com
A IPAM/PAM pode ser usada como uma alternativa à radiação de mama total em pacientes altamente selecionados e de baixo risco com linfonodos axilares negativos:
Os critérios para IPAM/PAM incluem todos os seguintes: BRCA negativo, idade ≥40 anos, carcinoma ductal invasivo de grau 1 a 2, tamanho do tumor ≤2 cm, margens negativas ≥2 mm, doença HR positiva e sem invasão linfovascular.[373]Shaitelman SF, Anderson BM, Arthur DW, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2024 Mar-Apr;14(2):112-32.
https://www.practicalradonc.org/article/S1879-8500(23)00296-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37977261?tool=bestpractice.com
As diretrizes sugerem que IPAM/PAM também pode ser considerada com cautela em algumas pacientes com doença de grau 3, ou doença HR negativa, ou tamanho do tumor >2-3 cm; no entanto, pode haver um aumento do risco de recorrência, especialmente quando mais de um desses fatores estão presentes.[373]Shaitelman SF, Anderson BM, Arthur DW, et al. Partial breast irradiation for patients with early-stage invasive breast cancer or ductal carcinoma in situ: an ASTRO clinical practice guideline. Pract Radiat Oncol. 2024 Mar-Apr;14(2):112-32.
https://www.practicalradonc.org/article/S1879-8500(23)00296-5/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/37977261?tool=bestpractice.com
IPAM/PAM usando técnicas de radioterapia por feixe externo (EBRT) (radioterapia conformacional tridimensional ou radioterapia de intensidade modulada) ou braquiterapia multicateter tem taxas de recorrência semelhantes à radioterapia de mama total em pacientes de baixo risco.[383]Meattini I, Marrazzo L, Saieva C, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020 Dec 10;38(35):4175-83.
https://www.doi.org/10.1200/JCO.20.00650
http://www.ncbi.nlm.nih.gov/pubmed/32840419?tool=bestpractice.com
[384]Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019 Dec 14;394(10215):2165-72.
http://www.ncbi.nlm.nih.gov/pubmed/31813635?tool=bestpractice.com
[385]Coles CE, Griffin CL, Kirby AM, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017 Sep 9;390(10099):1048-60.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5594247
http://www.ncbi.nlm.nih.gov/pubmed/28779963?tool=bestpractice.com
[386]Strnad V, Polgár C, Ott OJ, et al. Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial. Lancet Oncol. 2023 Mar;24(3):262-72.
http://www.ncbi.nlm.nih.gov/pubmed/36738756?tool=bestpractice.com
[387]Offersen BV, Alsner J, Nielsen HM, et al. Partial breast irradiation versus whole breast irradiation for early breast cancer patients in a randomized phase III trial: the Danish Breast Cancer Group partial breast irradiation trial. J Clin Oncol. 2022 Dec 20;40(36):4189-97.
https://ascopubs.org/doi/10.1200/JCO.22.00451
http://www.ncbi.nlm.nih.gov/pubmed/35930754?tool=bestpractice.com
[388]Polgár C, Major T, Takácsi-Nagy Z, et al. Breast-conserving surgery followed by partial or whole breast irradiation: twenty-year results of a phase 3 clinical study. Int J Radiat Oncol Biol Phys. 2021 Mar 15;109(4):998-1006.
http://www.ncbi.nlm.nih.gov/pubmed/33186620?tool=bestpractice.com
[389]Shumway DA, Corbin KS, Farah MH, et al. Partial breast irradiation compared with whole breast irradiation: a systematic review and meta-analysis. J Natl Cancer Inst. 2023 Sep 7;115(9):1011-9.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10483267
http://www.ncbi.nlm.nih.gov/pubmed/37289549?tool=bestpractice.com
A EBRT uma vez ao dia ou em dias alternados está associada à melhora da cosmese e à redução de toxicidades agudas e tardias em comparação à radioterapia de mama total.[383]Meattini I, Marrazzo L, Saieva C, et al. Accelerated partial-breast irradiation compared with whole-breast irradiation for early breast cancer: long-term results of the randomized phase III APBI-IMRT-Florence Trial. J Clin Oncol. 2020 Dec 10;38(35):4175-83.
https://www.doi.org/10.1200/JCO.20.00650
http://www.ncbi.nlm.nih.gov/pubmed/32840419?tool=bestpractice.com
[385]Coles CE, Griffin CL, Kirby AM, et al. Partial-breast radiotherapy after breast conservation surgery for patients with early breast cancer (UK IMPORT LOW trial): 5-year results from a multicentre, randomised, controlled, phase 3, non-inferiority trial. Lancet. 2017 Sep 9;390(10099):1048-60.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5594247
http://www.ncbi.nlm.nih.gov/pubmed/28779963?tool=bestpractice.com
[390]Franceschini D, Loi M, Chiola I, et al. Preliminary results of a randomized study on postmenopausal women with early stage breast cancer: adjuvant hypofractionated whole breast irradiation versus accelerated partial breast irradiation (HYPAB Trial). Clin Breast Cancer. 2021 Jun;21(3):231-8.
http://www.ncbi.nlm.nih.gov/pubmed/33121891?tool=bestpractice.com
Esquemas de duas vezes ao dia estão associados a pior toxicidade tardia e cosmese.[372]Haussmann J, Budach W, Corradini S, et al. Comparison of adverse events in partial- or whole breast radiotherapy: investigation of cosmesis, toxicities and quality of life in a meta-analysis of randomized trials. Radiat Oncol. 2023 Nov 2;18(1):181.
https://pmc.ncbi.nlm.nih.gov/articles/PMC10623828
http://www.ncbi.nlm.nih.gov/pubmed/37919752?tool=bestpractice.com
[384]Whelan TJ, Julian JA, Berrang TS, et al. External beam accelerated partial breast irradiation versus whole breast irradiation after breast conserving surgery in women with ductal carcinoma in situ and node-negative breast cancer (RAPID): a randomised controlled trial. Lancet. 2019 Dec 14;394(10215):2165-72.
http://www.ncbi.nlm.nih.gov/pubmed/31813635?tool=bestpractice.com
A braquiterapia com múltiplos cateteres demonstrou desfechos de toxicidade tardia semelhantes à radioterapia de mama total, com melhor cosmese.[386]Strnad V, Polgár C, Ott OJ, et al. Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial. Lancet Oncol. 2023 Mar;24(3):262-72.
http://www.ncbi.nlm.nih.gov/pubmed/36738756?tool=bestpractice.com
[388]Polgár C, Major T, Takácsi-Nagy Z, et al. Breast-conserving surgery followed by partial or whole breast irradiation: twenty-year results of a phase 3 clinical study. Int J Radiat Oncol Biol Phys. 2021 Mar 15;109(4):998-1006.
http://www.ncbi.nlm.nih.gov/pubmed/33186620?tool=bestpractice.com
[391]Polgár C, Ott OJ, Hildebrandt G, et al. Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2017 Feb;18(2):259-68.
http://www.ncbi.nlm.nih.gov/pubmed/28094198?tool=bestpractice.com
Nenhum estudo comparou diretamente técnicas e esquemas de IPAM/PAM.
Radioterapia pós-lumpectomia: linfonodos axilares positivos
A radioterapia de mama total, com ou sem reforço tumoral, é recomendada para pacientes com linfonodos axilares positivos.
Além disso, a ILR abrangente, incluindo axila não dissecada em risco, é recomendada para aquelas com ≥4 linfonodos positivos. A ILR, com ou sem axila não dissecada, pode ser considerada para aquelas com 1-3 linfonodos positivos. As decisões sobre a inclusão dos linfonodos mamários internos na ILR devem ser individualizadas, levando em consideração os riscos, incluindo toxicidade cardíaca e pulmonar.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Esquemas hipofracionados (com menos frações de dose mais altas em um período mais curto) são recomendados para radioterapia de mama total.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[376]Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013 Oct;14(11):1086-94.
https://www.doi.org/10.1016/S1470-2045(13)70386-3
http://www.ncbi.nlm.nih.gov/pubmed/24055415?tool=bestpractice.com
[375]Bentzen SM, Agrawal RK, Aird EG, et al; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncol. 2008 Apr;9(4):331-41.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(08)70077-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/18356109?tool=bestpractice.com
[377]Bentzen SM, Agrawal RK, Aird EG, et al; START Trialists' Group. The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet. 2008 Mar 29;371(9618):1098-107.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60348-7/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/18355913?tool=bestpractice.com
[378]Whelan TJ, Pignol JP, Levine MN, et al. Long-term results of hypofractionated radiation therapy for breast cancer. N Engl J Med. 2010 Feb 11;362(6):513-20.
https://www.nejm.org/doi/full/10.1056/NEJMoa0906260
http://www.ncbi.nlm.nih.gov/pubmed/20147717?tool=bestpractice.com
[379]Hickey BE, James ML, Lehman M, et al. Hypofractionated radiation therapy for early breast cancer. Cochrane Database Syst Rev. 2016 Jul 18;(7):CD003860.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003860.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/27425588?tool=bestpractice.com
[
]
In women with early breast cancer who have undergone breast conserving surgery, how does hypofractionation compare with conventional fractionation?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.1501/fullMostre-me a resposta A radioterapia hipofracionada reduz o risco de edema mamário, telangiectasia e toxicidade aguda da radiação na pele em comparação com esquemas convencionais.[380]Andrade TRM, Fonseca MCM, Segreto HRC, et al. Meta-analysis of long-term efficacy and safety of hypofractionated radiotherapy in the treatment of early breast cancer. Breast. 2019 Dec;48:24-31.
http://www.ncbi.nlm.nih.gov/pubmed/31476695?tool=bestpractice.com
Radioterapia pós-mastectomia
A radioterapia após a mastectomia reduz o risco de recorrência local e aumenta as taxas de sobrevida em pacientes com câncer de mama positivo para linfonodos.[392]Whelan TJ, Julian J, Wright J, et al. Does locoregional radiation therapy improve survival in breast cancer? A meta-analysis. J Clin Oncol. 2000 Mar;18(6):1220-9.
http://www.ncbi.nlm.nih.gov/pubmed/10715291?tool=bestpractice.com
[393]Ragaz J, Olivotto IA, Spinelli JJ, et al. Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial. J Natl Cancer Inst. 2005 Jan 19;97(2):116-26.
https://academic.oup.com/jnci/article/97/2/116/2544050
http://www.ncbi.nlm.nih.gov/pubmed/15657341?tool=bestpractice.com
[394]Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. J Clin Oncol. 2016 Dec 20;34(36):4431-42.
https://ascopubs.org/doi/full/10.1200/JCO.2016.69.1188
http://www.ncbi.nlm.nih.gov/pubmed/27646947?tool=bestpractice.com
[395]McGale P, Taylor C, Correa C, et al; EBCTCG (Early Breast Cancer Trialists' Collaborative Group). Effect of radiotherapy after mastectomy and axillary surgery on 10-year recurrence and 20-year breast cancer mortality: meta-analysis of individual patient data for 8135 women in 22 randomised trials. Lancet. 2014 Jun 21;383(9935):2127-35.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)60488-8/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/24656685?tool=bestpractice.com
[396]Wang SL, Fang H, Song YW, et al. Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):352-60.
http://www.ncbi.nlm.nih.gov/pubmed/30711522?tool=bestpractice.com
A radioterapia após a mastectomia (incluindo irradiação da parede torácica, cicatriz de mastectomia, locais de dreno, áreas infraclavicular e supraclavicular, nódulos mamários internos e leito axilar) é recomendada para pacientes positivas para linfonodos (particularmente se ≥4 linfonodos positivos) e para as pacientes negativas para linfonodos com tumores >5 cm ou margens cirúrgicas positivas.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[394]Recht A, Comen EA, Fine RE, et al. Postmastectomy radiotherapy: an American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology focused guideline update. J Clin Oncol. 2016 Dec 20;34(36):4431-42.
https://ascopubs.org/doi/full/10.1200/JCO.2016.69.1188
http://www.ncbi.nlm.nih.gov/pubmed/27646947?tool=bestpractice.com
[397]Budach W, Matuschek C, Bölke E, et al. DEGRO practical guidelines for radiotherapy of breast cancer V: therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases. Strahlenther Onkol. 2015 Aug;191(8):623-33.
https://link.springer.com/article/10.1007%2Fs00066-015-0843-1
http://www.ncbi.nlm.nih.gov/pubmed/25963557?tool=bestpractice.com
A irradiação da parede torácica pode ser considerada em pacientes negativas para linfonodos com tumores ≤5 e margens cirúrgicas negativas que sejam ≤1 mm (e a ILR também é considerada se apresentarem características de alto risco adicionais). Pacientes negativas para linfonodos com margens ≥1 mm podem ser consideradas para radioterapia apenas se apresentarem múltiplas características de alto risco (por exemplo, tumores centrais/mediais ou tumores ≥2 cm e de grau 3, negativo para ER ou invasão linfovascular).[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
Algumas diretrizes recomendam esquemas hipofracionados e ultra-hipofracionados para a radiação da parede torácica, assim como para a radiação de mama total.[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
A radioterapia axilar está associada a uma sobrevida global de 10 anos, à sobrevida distante livre de metástase e à recorrência locorregional à DLA em mulheres com BLS positiva. O segundo câncer primário, inclusive câncer de mama primário contralateral, ocorreu com um pouco mais de frequência no grupo de radioterapia axilar, comparado com o grupo de DLA.[398]Rutgers EJ, Donker M, Poncet C, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: 10 year follow up results of the EORTC AMAROS trial (EORTC 10981/22023). Paper presented at: 2018 San Antonio Breast Cancer Symposium. 2018. San Antonio, TX. Cancer Res. 2019 Feb;79(4 Suppl):Abstract GS4-01.
https://cancerres.aacrjournals.org/content/79/4_Supplement/GS4-01
Cuidados de suporte: saúde óssea
O câncer de mama pode ter um impacto negativo sobre a saúde dos ossos.[399]Kanis JA, McCloskey EV, Powles T, et al. A high incidence of vertebral fracture in women with breast cancer. Br J Cancer. 1999 Mar;79(7-8):1179-81.
http://www.ncbi.nlm.nih.gov/pubmed/10098755?tool=bestpractice.com
A incidência de fratura vertebral é, aproximadamente, 5 vezes maior em mulheres com câncer de mama não metastático (desde o momento do primeiro diagnóstico) que na população em geral.[399]Kanis JA, McCloskey EV, Powles T, et al. A high incidence of vertebral fracture in women with breast cancer. Br J Cancer. 1999 Mar;79(7-8):1179-81.
http://www.ncbi.nlm.nih.gov/pubmed/10098755?tool=bestpractice.com
O uso de terapia endócrina (por exemplo, inibidores da aromatase) reduz a densidade mineral óssea.[400]Eastell R, Hannon RA, Cuzick J, et al. Effect of an aromatase inhibitor on BMD and bone turnover markers: 2-year results of the Anastrozole, Tamoxifen, Alone or in Combination (ATAC) trial (18233230). J Bone Miner Res. 2006 Aug;21(8):1215-23.
https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.060508
http://www.ncbi.nlm.nih.gov/pubmed/16869719?tool=bestpractice.com
Os fatores de risco para osteoporose também devem ser levados em consideração, inclusive: estado menopausado, idade avançada, tabagismo atual, consumo excessivo de álcool, fraturas prévias não traumáticas na fase adulta, mobilidade prejudicada, aumento do risco de quedas, hipogonadismo, exposição de longo prazo a glicocorticoides, fratura do quadril parental e baixo peso corporal. Deve-se oferecer o exame de densitometria óssea a pacientes com câncer não metastático e um ou mais desses fatores de risco.[401]Shapiro CL, Van Poznak C, Lacchetti C, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol. 2019 Nov 1;37(31):2916-46.
https://ascopubs.org/doi/10.1200/JCO.19.01696
http://www.ncbi.nlm.nih.gov/pubmed/31532726?tool=bestpractice.com
As pacientes que recebem um inibidor da aromatase ou agente de supressão da função ovariana devem ter ingestões de cálcio e vitamina D adequadas, além de se submeterem a uma avaliação regular da densidade mineral óssea (por exemplo, com absorciometria por dupla emissão de raios X [DEXA]).[401]Shapiro CL, Van Poznak C, Lacchetti C, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol. 2019 Nov 1;37(31):2916-46.
https://ascopubs.org/doi/10.1200/JCO.19.01696
http://www.ncbi.nlm.nih.gov/pubmed/31532726?tool=bestpractice.com
[402]Eisen A, Somerfield MR, Accordino MK, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J Clin Oncol. 2022 Mar 1;40(7):787-800.
https://ascopubs.org/doi/10.1200/JCO.21.02647
http://www.ncbi.nlm.nih.gov/pubmed/35041467?tool=bestpractice.com
Os agentes modificadores de osso (por exemplo, bifosfonato, denosumabe) podem ser considerados para prevenir a perda óssea e reduzir o risco de fratura óssea em mulheres menopausadas com câncer de mama positivo para HR que recebem terapia endócrina adjuvante.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[402]Eisen A, Somerfield MR, Accordino MK, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J Clin Oncol. 2022 Mar 1;40(7):787-800.
https://ascopubs.org/doi/10.1200/JCO.21.02647
http://www.ncbi.nlm.nih.gov/pubmed/35041467?tool=bestpractice.com
[403]Brufsky AM, Harker WG, Beck JT, et al. Final 5-year results of Z-FAST trial: adjuvant zoledronic acid maintains bone mass in postmenopausal breast cancer patients receiving letrozole. Cancer. 2012 Mar 1;118(5):1192-201.
http://www.ncbi.nlm.nih.gov/pubmed/21987386?tool=bestpractice.com
[404]Coleman RE, Marshall H, Cameron D et al. Breast-cancer adjuvant therapy with zoledronic acid. N Engl J Med. 2011 Oct 13;365(15):1396-405.
http://www.ncbi.nlm.nih.gov/pubmed/21995387?tool=bestpractice.com
[405]Coleman R, de Boer R, Eidtmann H, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013 Feb;24(2):398-405.
http://www.ncbi.nlm.nih.gov/pubmed/23047045?tool=bestpractice.com
[406]O'Carrigan B, Wong MH, Willson ML, et al. Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev. 2017 Oct 30;(10):CD003474.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003474.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/29082518?tool=bestpractice.com
[407]Gnant M, Pfeiler G, Steger GG, et al. Adjuvant denosumab in postmenopausal patients with hormone receptor-positive breast cancer (ABCSG-18): disease-free survival results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):339-51.
http://www.ncbi.nlm.nih.gov/pubmed/30795951?tool=bestpractice.com
[
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What are the effects of bisphosphonates in women with early breast cancer?/cca.html?targetUrl=https://cochranelibrary.com/cca/doi/10.1002/cca.1947/fullMostre-me a resposta
A terapia adjuvante com bifosfonatos deve ser discutida com todas as pacientes menopausadas (naturais ou induzidas por terapia) com câncer de mama primário, independentemente do status status de HR e do status de HER2, que sejam candidatas a receber terapia sistêmica adjuvante.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[402]Eisen A, Somerfield MR, Accordino MK, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J Clin Oncol. 2022 Mar 1;40(7):787-800.
https://ascopubs.org/doi/10.1200/JCO.21.02647
http://www.ncbi.nlm.nih.gov/pubmed/35041467?tool=bestpractice.com
[405]Coleman R, de Boer R, Eidtmann H, et al. Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): final 60-month results. Ann Oncol. 2013 Feb;24(2):398-405.
http://www.ncbi.nlm.nih.gov/pubmed/23047045?tool=bestpractice.com
[406]O'Carrigan B, Wong MH, Willson ML, et al. Bisphosphonates and other bone agents for breast cancer. Cochrane Database Syst Rev. 2017 Oct 30;(10):CD003474.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003474.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/29082518?tool=bestpractice.com
[408]Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials. Lancet. 2015 Oct 3;386(10001):1353-61.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60908-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26211824?tool=bestpractice.com
[409]Gralow JR, Barlow WE, Paterson AHG, et al. Phase III randomized trial of bisphosphonates as adjuvant therapy in breast cancer: S0307. J Natl Cancer Inst. 2020 Jul 1;112(7):698-707.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7357327
http://www.ncbi.nlm.nih.gov/pubmed/31693129?tool=bestpractice.com
[410]Friedl TWP, Fehm T, Müller V, et al. Prognosis of patients with early breast cancer receiving 5 years vs 2 years of adjuvant bisphosphonate treatment: a phase 3 randomized clinical trial. JAMA Oncol. 2021 Aug 1;7(8):1149-57.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227465
http://www.ncbi.nlm.nih.gov/pubmed/34165508?tool=bestpractice.com
Recomenda-se o uso precoce.[402]Eisen A, Somerfield MR, Accordino MK, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: ASCO-OH (CCO) guideline update. J Clin Oncol. 2022 Mar 1;40(7):787-800.
https://ascopubs.org/doi/10.1200/JCO.21.02647
http://www.ncbi.nlm.nih.gov/pubmed/35041467?tool=bestpractice.com
A ASCO recomenda oferecer agentes modificadores do osso a pacientes com:[401]Shapiro CL, Van Poznak C, Lacchetti C, et al. Management of osteoporosis in survivors of adult cancers with nonmetastatic disease: ASCO clinical practice guideline. J Clin Oncol. 2019 Nov 1;37(31):2916-46.
https://ascopubs.org/doi/10.1200/JCO.19.01696
http://www.ncbi.nlm.nih.gov/pubmed/31532726?tool=bestpractice.com
Osteoporose confirmada por densitometria óssea
Uma probabilidade de 10 anos ≥20% para fratura osteoporótica importante (com base na ferramenta FRAX adaptada aos EUA), ou
Probabilidade ≥3% em 10 anos para fratura do quadril (com base na ferramenta FRAX adaptada aos EUA).
Os médicos devem estimular as pacientes a abandonar o hábito de fumar, limitar o consumo de bebidas alcoólicas e envolver-se em uma variedade de tipos de exercício.
Em janeiro de 2024, a FDA alertou sobre um aumento do risco de hipocalcemia grave em pacientes com doença renal crônica avançada que estão recebendo denosumabe (Prolia® 60 mg/mL aprovado para tratamento para aumentar a massa óssea em mulheres com alto risco de fratura recebendo terapia adjuvante com inibidor da aromatase para câncer de mama).[411]U.S. Food and Drug Administration. FDA adds Boxed Warning for increased risk of severe hypocalcemia in patients with advanced chronic kidney disease taking osteoporosis medicine Prolia (denosumab). Feb 2024 [internet publication].
https://www.fda.gov/drugs/drug-safety-and-availability/fda-adds-boxed-warning-increased-risk-severe-hypocalcemia-patients-advanced-chronic-kidney-disease
Dois estudos de segurança demonstraram um aumento significativo no risco de hipocalcemia grave em pacientes tratados com denosumabe em comparação com aqueles tratados com bifosfonatos, com o risco mais elevado relatado em pacientes com doença renal avançada, particularmente aqueles em diálise. A hipocalcemia grave foi mais comum naqueles com distúrbios minerais e ósseos. Antes de prescrever denosumabe, os profissionais da saúde devem avaliar a função renal e os níveis de cálcio, e considerar outras opções de tratamento para pacientes em risco. Durante o tratamento, o monitoramento frequente do cálcio sanguíneo e o tratamento imediato da hipocalcemia grave são essenciais. A FDA não emitiu um alerta em relação à marca de denosumabe aprovada especificamente para a prevenção de eventos adversos relacionados ao esqueleto nas neoplasias malignas (Xgeva® 120 mg/1.7 mL).
Doença recorrente
Índices de recorrência de aproximadamente 1% a 2% por ano ocorrem nas pacientes tratadas com lumpectomia. Aquelas com aumento do risco de recorrência incluem pacientes mais jovens, aquelas com margens cirúrgicas positivas, aquelas com um componente intraductal extenso e aquelas não submetidas a radioterapia. Essas recorrências tendem a ocorrer dentro de 3-5 anos após a conclusão da terapia e são mais comuns no mesmo quadrante da lesão inicial. Em pacientes tratadas com mastectomia, 90% das recorrências locais ocorrem dentro dos 5 primeiros anos. O reconhecimento imediato da recorrência do tumor é o objetivo do rigoroso acompanhamento por exames de imagem.[412]American College of Radiology. ACR appropriateness criteria: stage I breast cancer: initial workup and surveillance for local recurrence and distant metastases in asymptomatic women. 2019 [internet publication].
https://acsearch.acr.org/docs/69496/Narrative
O tratamento de recorrência locorregional é individualizado e requer a coordenação de uma equipe multidisciplinar para determinar a função ideal e o momento da terapia local (cirurgia e radioterapi)a e da terapia sistêmica.
As considerações para terapia local incluem determinar se a recorrência foi em um local irradiado anteriormente, a presença ou ausência de metástases à distância e o número de locais com doença recorrente. Outras considerações incluem a capacidade de atingir margens negativas e se a paciente precisará de terapia sistêmica antes da ressecção.[413]American College of Radiology. ACR appropriateness criteria: local-regional recurrence (LRR) and salvage surgery - breast cancer. 2013 [internet publication].
https://acsearch.acr.org/docs/69387/Narrative
A terapia sistêmica após recorrência deve levar em consideração o tratamento prévio. Para recorrências locorregionais isoladas de câncer de mama totalmente ressecadas, a quimioterapia adjuvante deve ser considerada.[414]Aebi S, Gelber S, Anderson SJ, et al; CALOR investigators. Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol. 2014 Feb;15(2):156-63.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982874
http://www.ncbi.nlm.nih.gov/pubmed/24439313?tool=bestpractice.com
Câncer de mama masculino
Devido à raridade do câncer de mama em homens (<1%), a maioria das recomendações de tratamento baseia-se em estudos retrospectivos e na extrapolação de estudos sobre câncer de mama feminino.[415]Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020 Jun 1;38(16):1849-63.
https://ascopubs.org/doi/full/10.1200/JCO.19.03120
http://www.ncbi.nlm.nih.gov/pubmed/32058842?tool=bestpractice.com
[416]Weiss JR, Moysich KB, Swede H. Epidemiology of male breast cancer. Cancer Epidemiol Biomarkers Prev. 2005 Jan;14(1):20-6.
https://cebp.aacrjournals.org/content/14/1/20.long
http://www.ncbi.nlm.nih.gov/pubmed/15668471?tool=bestpractice.com
[417]Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018 Feb 1;29(2):405-17.
https://www.annalsofoncology.org/article/S0923-7534(19)35037-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29092024?tool=bestpractice.com
Geralmente é oferecida a mastectomia total para os homens com câncer de mama invasivo primário.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
A mastectomia radical não parece melhorar o risco de recorrência ou sobrevida, comparada à mastectomia total; no entanto, pode ser considerada para pacientes com doença que envolve o músculo peitoral maior ou gânglios de Rotter.[418]Borgen PI, Wong GY, Vlamis V, et al. Current management of male breast cancer. A review of 104 cases. Ann Surg. 1992 May;215(5):451-7.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1242473/pdf/annsurg00087-0073.pdf
http://www.ncbi.nlm.nih.gov/pubmed/1319699?tool=bestpractice.com
A cirurgia conservadora da mama é cada vez mais realizada em homens (normalmente pacientes com idade avançada), e os estudos sugerem que os desfechos são similares aos da mastectomia.[417]Cardoso F, Bartlett JMS, Slaets L, et al. Characterization of male breast cancer: results of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Ann Oncol. 2018 Feb 1;29(2):405-17.
https://www.annalsofoncology.org/article/S0923-7534(19)35037-9/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29092024?tool=bestpractice.com
[419]Cloyd JM, Hernandez-Boussard T, Wapnir IL. Outcomes of partial mastectomy in male breast cancer patients: analysis of SEER, 1983-2009. Ann Surg Oncol. 2013 May;20(5):1545-50.
http://www.ncbi.nlm.nih.gov/pubmed/23460016?tool=bestpractice.com
[420]Sauder CAM, Bateni SB, Davidson AJ, et al. Breast conserving surgery compared with mastectomy in male breast cancer: a brief systematic review. Clin Breast Cancer. 2020 Jun;20(3):e309-14.
http://www.ncbi.nlm.nih.gov/pubmed/32171701?tool=bestpractice.com
As decisões sobre a cirurgia conservadora da mama devem ser tomadas usando-se critérios similares aos para mulheres.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
O papel da BLS e da DLA em homens com câncer de mama invasivo primário segue os mesmos princípios segue os mesmos princípios adotados para as mulheres. A eficácia da BLS parece ser similar para homens e mulheres com doença clinicamente negativa para linfonodos.[421]Rusby JE, Smith BL, Dominguez FJ, et al. Sentinel lymph node biopsy in men with breast cancer: a report of 31 consecutive procedures and review of the literature. Clin Breast Cancer. 2006 Dec;7(5):406-10.
http://www.ncbi.nlm.nih.gov/pubmed/17239266?tool=bestpractice.com
[422]Giordano SH, Perkins GH, Broglio K, et al. Adjuvant systemic therapy for male breast carcinoma. Cancer. 2005 Dec 1;104(11):2359-64.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.21526
http://www.ncbi.nlm.nih.gov/pubmed/16270318?tool=bestpractice.com
[423]Cimmino VM, Degnim AC, Sabel MS, et al. Efficacy of sentinel lymph node biopsy in male breast cancer. J Surg Oncol. 2004 May 1;86(2):74-7.
http://www.ncbi.nlm.nih.gov/pubmed/15112248?tool=bestpractice.com
[424]Boughey JC, Bedrosian I, Meric-Bernstam F, et al. Comparative analysis of sentinel lymph node operation in male and female breast cancer patients. J Am Coll Surg. 2006 Oct;203(4):475-80.
http://www.ncbi.nlm.nih.gov/pubmed/17000390?tool=bestpractice.com
A quimioterapia (combinada com terapia direcionada ao HER2, em caso de positivo para HER2) é recomendada para homens com câncer de mama, seguindo os mesmos princípios de mulheres com câncer de mama.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[422]Giordano SH, Perkins GH, Broglio K, et al. Adjuvant systemic therapy for male breast carcinoma. Cancer. 2005 Dec 1;104(11):2359-64.
https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.21526
http://www.ncbi.nlm.nih.gov/pubmed/16270318?tool=bestpractice.com
Tamoxifeno adjuvante por 5 anos é recomendado para homens com câncer de mama positivo para HR.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[142]Loibl S, André F, Bachelot T, et al. Early breast cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024 Feb;35(2):159-82.
https://www.esmo.org/guidelines/guidelines-by-topic/esmo-clinical-practice-guidelines-breast-cancer/early-breast-cancer
http://www.ncbi.nlm.nih.gov/pubmed/38101773?tool=bestpractice.com
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com
[202]National Institute for Health and Care Excellence. Early and locally advanced breast cancer: diagnosis and management. Jun 2023 [internet publication].
https://www.nice.org.uk/guidance/ng101
[415]Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020 Jun 1;38(16):1849-63.
https://ascopubs.org/doi/full/10.1200/JCO.19.03120
http://www.ncbi.nlm.nih.gov/pubmed/32058842?tool=bestpractice.com
Em estudos retrospectivos, o tamoxifeno foi associado a uma sobrevida atuarial de 5 anos de 61% versus 44% para controles históricos (P=0.006).[425]Ribeiro G, Swindell R. Adjuvant tamoxifen for male breast cancer (MBC). Br J Cancer. 1992 Feb;65(2):252-4.
http://www.ncbi.nlm.nih.gov/pubmed/1739625?tool=bestpractice.com
O tamoxifeno adjuvante com agente único proporciona desfechos superiores comparado aos inibidores da aromatase adjuvantes em homens com câncer de mama positivo para HR.[426]Eggemann H, Ignatov A, Smith BJ, et al. Adjuvant therapy with tamoxifen compared to aromatase inhibitors for 257 male breast cancer patients. Breast Cancer Res Treat. 2013 Jan;137(2):465-70.
http://www.ncbi.nlm.nih.gov/pubmed/23224235?tool=bestpractice.com
O uso de radioterapia para homens com câncer de mama segue os mesmos princípios de mulheres com câncer de mama.[124]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
[200]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020 Dec;31(12):1623-49.
https://www.annalsofoncology.org/article/S0923-7534(20)42460-3/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32979513?tool=bestpractice.com