History and exam
Key diagnostic factors
common
presence of risk factors
Key risk factors for developing breast cancer include: female sex, age >50 years, family history of breast and/or ovarian cancer, and family and/or personal history of breast cancer susceptibility genes.[4][15][17][19][20][21][26][27]
Risk factors for developing metastatic disease in the presence of breast cancer include tumour >5 cm in diameter, high number of positive axillary lymph nodes (e.g., >10), lymphovascular invasion, and high-risk gene signatures.[28][29][30][31][32][33][34][35]
bone pain
May be due to disease spread to bone.[46]
pleural effusion
Pleural effusion in a patient with confirmed metastatic breast cancer suggests possible disease in the pleural cavity.
A sample of pleural fluid should be sent for cytological assessment to determine if malignant cells are present. However, a negative pleural cytology does not exclude a malignant pleural effusion.
uncommon
palpable mass after treatment of the primary tumour
May demonstrate recurrent disease.[47]
Other diagnostic factors
common
shortness of breath
Commonly secondary to pleural effusions.[46]
Less commonly due to lung metastases.
cough (non-productive)
May occur secondary to pleural effusions, or due to lung metastases or lymphangitic carcinomatosis.
anorexia
General symptom of metastatic breast cancer.
Common in the terminal stage of the disease but less common in the early stage.
weight loss
General sign of metastatic breast cancer.
Often related to lack of appetite.
uncommon
neurological symptoms (e.g., neuralgic pain, weakness, headaches, seizures)
Suggests possible brain or peripheral nervous system metastases.[46]
Risk factors
strong
age >50 years
family history of breast, ovarian, pancreatic, and/or prostate cancer
Breast cancer risk increases if there is a family history of breast cancer.
The magnitude of risk increases with the number of affected relatives and the closeness of the relationship. Specific family history associated with increased risk for breast cancer includes one or more close blood relative(s) with: breast cancer before age 50 years; history of male breast cancer, ovarian cancer, pancreatic cancer, or prostate cancer (with metastatic, or high- or very-high-risk group); ≥3 diagnoses of breast and/or prostate cancer on the same side of the family; Ashkenazi Jewish ancestry.[19]
breast cancer susceptibility genes (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53)
An estimated 5% to 10% of breast cancer cases are hereditary.[20] BRCA1 and BRCA2 germline mutations are the most common cause of hereditary breast cancer.[21]
Testing for high-penetrance breast cancer susceptibility genes (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, and TP53) is indicated in certain patients with a personal breast cancer history, or with a family history of breast, ovarian, pancreatic, and/or prostate cancer, or a family history of a pathogenic variant in a cancer susceptibility gene (see Primary invasive breast cancer [Screening]).[19][22][23][24][25]
Patients with metastatic breast cancer (MBC) should be considered for germline testing for mutations in high-penetrance breast cancer susceptibility genes.[19][26]
Mutations in these genes can inform prognosis and management decisions, and may also highlight risk among family members. Testing for BRCA1 and BRCA2 germline mutations is required to identify those eligible for poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitor therapy.[19][25][26][27]
tumour >5 cm in diameter
high number of positive axillary lymph nodes (e.g., >10)
lymphovascular invasion
The presence of this finding on histology increases risk of tumour recurrence (local or metastatic) and death.[32]
high-risk 70-gene signature
The 70-gene signature assay (Mammaprint®) can predict the risk of disease recurrence (metastasis) in post-menopausal women or women aged >50 years who have early-stage, node-negative breast cancer.[33]
high-risk 21-gene signature
The 21-gene signature assay (Oncotype DX®) can predict the risk of disease recurrence (metastasis) in patients with early-stage, hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer.[34]
The 21-gene assay recurrence score ranges from 0 to 100. Recurrence score (≥26) indicates more aggressive tumour characteristics, and is predictive of chemotherapy benefit. Low recurrence score (0 to 10) is prognostic for reduced risk of distant recurrence (2% to 3%) at 10 years that is unlikely to be influenced by adjuvant chemotherapy.[34] Among women with a midrange recurrence score (11 to 25), adjuvant endocrine therapy and chemoendocrine therapy were similarly effective.[34]
high-risk PAM50 gene signature
The PAM50-gene signature assay (Prosigna®) can predict the risk of disease recurrence (metastasis) in patients with hormone receptor-positive breast cancer.[35]
Score ranges from 0 to 100. Node-negative cancers are classified as low risk (0-40), intermediate risk (41-60), or high risk (61-100). Node-positive cancers (1-3 nodes) are classified as low risk (0-40) or high risk (41-100).
In node-negative patients, 10-year risk of distant recurrence was 5.0% and 17.8% for patients with low or high risk of recurrence scores, respectively.[35] In node-positive patients (1-3), 10-year risk of distant recurrence was 3.5% in the low-risk group and 22.1% for high risk patients.
weak
Lynch syndrome (hereditary non-polyposis colorectal cancer)
CHEK2 mutations
ATM mutations
minimal residual disease (MRD)
The detection of MRD in the bone marrow of patients with breast cancer, after adjuvant therapy, has been associated with shorter disease-free survival, in some but not all studies.[41]
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