Breast cancer in situ

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

women with low-risk ductal carcinoma in situ (DCIS)

1st line – surgical excision or mastectomy ± breast reconstruction

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1st line –

surgical excision or mastectomy ± breast reconstruction

The primary treatment options for women with low-risk DCIS (e.g., DCIS that is screen detected, unifocal, unicentric, low to intermediate grade, and ≤2.5 cm) are breast-conserving therapy (involving wide local surgical excision of the tumour [lumpectomy] followed by adjuvant radiotherapy), or total mastectomy (with or without breast reconstruction).[66]

The preferred approach is determined through a shared decision-making process between the patient and treating clinicians. Both approaches have demonstrated equivalent outcomes in terms of overall survival.[66][106][107]

Guidelines generally recommend breast-conserving therapy as the primary treatment for most patients with low-risk DCIS.[66][108]

The preferred post-surgical margin following breast-conserving surgery for DCIS is ≥2 mm if whole breast radiotherapy is planned.[108][109] The risk of relapse increases with margins ≤2 mm.[66]

Breast reconstruction should be discussed with all patients who plan to undergo mastectomy. It can be performed at the time of mastectomy (immediate reconstruction) or at a later date (delayed reconstruction).

Select patients with low-risk DCIS may be considered for breast-conserving surgery alone without adjuvant radiotherapy (e.g., those with clear margins ≥3 mm).[66][111][110] However, this approach is controversial because adjuvant radiotherapy decreases the risk of disease recurrence (local and distant) in various sub-groups of women with DCIS.[112][111] [ ]

Guidelines advise that breast-conserving surgery alone should be considered only for patients with a low risk of recurrence and following a discussion between the physician and patient on the risks and benefits.[66] If breast-conserving surgery alone is undertaken, then frequent follow-up should be performed during the first 3-5 years in order to detect disease recurrence early.

Consider – axillary lymph node surgical staging

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Consider –

axillary lymph node surgical staging

Additional treatment recommended for SOME patients in selected patient group

Axillary lymph node surgical staging is controversial in patients with DCIS.[117][118]

Sentinel lymph node biopsy (SLNB) may be considered in the setting of: mastectomy for DCIS; excision in an anatomical location compromising the performance of a future SLNB procedure; or oncoplastic breast conserving surgery.[66]

SLNB should not be routinely performed in women with preoperative (biopsy-determined) pure DCIS who are undergoing breast-conserving surgery, but it may be considered if there is high suspicion for invasive disease or axillary metastasis (e.g., palpable mass, extensive microcalcifications).[66][95][96]

Consider – adjuvant radiotherapy

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Consider –

adjuvant radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Options include whole breast radiotherapy (WBRT), radiotherapy boost to the tumour bed, accelerated partial breast irradiation/partial breast irradiation (APBI/PBI).

Adjuvant WBRT following lumpectomy is recommended in order to treat microscopic disease, and to reduce the risk of ipsilateral recurrence.[66] Systematic reviews and meta-analyses report reduced risk for ipsilateral recurrence in women with DCIS who received adjuvant radiotherapy following breast-conserving surgery compared with those who did not receive radiotherapy.[120][119] In patients with DCIS, treatment with lumpectomy and radiotherapy is associated with a significant reduction in 15-year breast cancer mortality rate compared with lumpectomy alone or mastectomy alone.[121]

Radiotherapy boost to the tumour bed may be offered along with adjuvant WBRT, depending on individual patient factors and patient preference.[66][108] In one multi-centre phase 3 randomised study, tumour bed boost after WBRT reduced local recurrence in women with resected non-low-risk DCIS (5-year free-from-local-recurrence rate 92.7% in the no-boost group compared with 97.1% in the boost group).[122] The boost group experienced higher rates of breast pain and induration.

Accelerated partial breast irradiation/partial breast irradiation (APBI/PBI) may be an alternative to adjuvant WBRT in patients with low-risk DCIS and all of the following factors: BRCA negative; age ≥40 years; low to intermediate grade DCIS; tumour size ≤2 cm; negative margins.[123]

Guidelines suggest that APBI/PBI may also be considered with caution in some patients with high-grade (grade 3) disease or tumour size >2 to 3 cm, however there may be an increased risk of recurrence, especially when both of these factors are present.[123]

External beam radiotherapy (EBRT) techniques, such as 3-D conformal radiotherapy (3-D CRT) or intensity modulated radiotherapy (IMRT), and multicatheter brachytherapy are recommended for APBI/PBI.[123] Single-entry catheter brachytherapy may be considered, although evidence from randomised controlled trials (RCTs) is lacking.

PBI delivers radiation specifically to the tumour or tumour bed and surrounding breast tissue; APBI involves larger than standard doses of radiation over a shorter time period. APBI/PBI spares healthy breast tissue, and reduces treatment time and some treatment-related adverse effects (e.g., acute skin toxicity).[123][124]

RCTs with long-term follow-up, and one systematic review and meta-analysis, suggest that APBI/PBI using EBRT or brachytherapy techniques has a similar recurrence rate to WBRT in patients with early stage breast cancer.[125][126][127][128][129][130][131] Sub-group analyses of patients with DCIS from two RCTs suggest little difference in recurrence rates up to 10 years.[125][132]

APBI/PBI using intraoperative radiotherapy may allow radiotherapy to be completed at the same time as surgery, but studies suggest it may be associated with a higher rate of recurrence compared with WBRT (with comparable overall mortality). It should therefore be used only as part of a clinical trial.[123][131][133][134][135]

No studies have directly compared APBI/PBI techniques and regimens. APBI/PBI using EBRT (3-D CRT or IMRT) given once daily or on alternate days is associated with improved cosmesis and reduced acute and late toxicities compared with WBRT.[126][129][136] Twice-daily EBRT regimens are associated with worse late toxicity and cosmesis.[124][125] APBI/PBI using multicatheter brachytherapy has shown similar late toxicity outcomes to WBRT, with comparable or improved cosmesis.[124][127][130][137]

Adverse effects of radiotherapy are localised to the area(s) through which the radiation passes. The most common acute adverse effects are skin changes (similar to sunburn) and fatigue. The skin may tan, either temporarily or permanently. The irradiated breast may appear smaller due to both surgical therapy and radiotherapy. In patients receiving WBRT, a small portion of the lung and ribs receive radiation, which can induce lung scarring and slightly increase the risk of rib fracture. Furthermore, the heart is incidentally exposed to small doses of radiation when treating left-sided breast cancers, which may increase the risk of ischaemic heart disease.[138] Risk of ischaemic heart disease may increase with increasing doses of radiation to the heart.[138] Hypofractionated and ultra-hypofractionated WBRT regimens and APBI/PBI minimise the dose and, therefore, sequelae.

Consider – adjuvant endocrine therapy

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Consider –

adjuvant endocrine therapy

Additional treatment recommended for SOME patients in selected patient group

Hormone (oestrogen) receptor status can guide decisions regarding use of adjuvant (post-operative) endocrine therapy to reduce the risk of ipsilateral recurrence and contralateral breast cancer. Improved survival has not been shown; therefore, the risks and benefits of adjuvant endocrine therapy should be discussed with the patient.[66][108]

For premenopausal women with oestrogen receptor (ER)-positive DCIS, tamoxifen for 5 years is considered first-line therapy for risk reduction of the ipsilateral breast after breast-conserving therapy (i.e., lumpectomy followed by adjuvant radiotherapy), and for risk reduction of the contralateral breast after either mastectomy or breast-conserving therapy has been completed.[66][108] Tamoxifen is effective in preventing recurrence in patients with ER-positive breast cancer (both invasive and non-invasive), as well as in decreasing the risk of ER-positive breast cancer developing in the contralateral breast.[150] [ ]

For postmenopausal women either tamoxifen or an aromatase inhibitor (e.g., anastrozole or exemestane) for 5 years is considered first-line therapy for risk reduction after surgery.[66][108] Aromatase inhibitors may be preferred for postmenopausal women who are aged <60 years or who have an increased risk of thromboembolism.[66][108][151] Bisphosphonates or denosumab should be considered to maintain or improve bone mineral density and to reduce risk of fractures in postmenopausal women receiving aromatase inhibitors.[66]

The efficacy of adjuvant endocrine therapy is independent of age.[152][153] Guidelines from the European Society of Breast Cancer Specialists suggest that aromatase inhibitors are slightly more beneficial than tamoxifen for women aged >70 years and preferred for high-risk patients, although choice of drug should take into account multimorbidity and recurrence risk.[152]

Primary options

tamoxifen: 20 mg orally once daily

anastrozole: 1 mg orally once daily

exemestane: 25 mg orally once daily

women with high-risk DCIS; all men with DCIS

1st line – mastectomy ± breast reconstruction

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1st line –

mastectomy ± breast reconstruction

Mastectomy is generally recommended for women with high-risk DCIS, and for men with DCIS.[16][72][140]

High-risk patients include those with: multicentric disease (DCIS in two or more quadrants); multifocal disease (two or more sites of disease in the same quadrant [mastectomy should be considered because it may not be feasible to surgically clear the disease and achieve a good cosmetic outcome with breast-conserving therapy]); a palpable mass and/or imaging showing a formed lesion on presentation; histologically high-grade DCIS (should be considered for mastectomy).[66][141]

Breast reconstruction should be discussed with all patients who plan to undergo mastectomy. It can be performed at the time of mastectomy (immediate reconstruction) or a later time (delayed reconstruction).

Consider – axillary lymph node surgical staging

Back

Consider –

axillary lymph node surgical staging

Additional treatment recommended for SOME patients in selected patient group

Sentinel lymph node biopsy (SLNB) should be considered in patients undergoing mastectomy.[66]

Performing an SLNB after mastectomy is impractical.

The likelihood that an initial diagnosis of DCIS will be upgraded to invasive breast cancer is greater if the disease is high grade, and/or the tumour is large (>2.5 cm based on imaging) or palpable.[142][143][144][145][146]

Consider – adjuvant radiotherapy

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Consider –

adjuvant radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Disease recurrence is low following total mastectomy for DCIS.[147][148]

Adjuvant radiotherapy is not required for DCIS treated with mastectomy unless disease is present near or at the chest wall, or if there is a substantial positive surgical margin.[149]

Hypofractionated and ultra-hypofractionated WBRT regimens minimise the dose and, therefore, sequelae.

Consider – adjuvant endocrine therapy

Back

Consider –

adjuvant endocrine therapy

Additional treatment recommended for SOME patients in selected patient group

For postmenopausal women with ER-positive DCIS, either tamoxifen or an aromatase inhibitor (e.g., anastrozole or exemestane) for 5 years is considered first-line therapy for risk reduction after surgery.[66][108] Aromatase inhibitors may be preferred for postmenopausal women who are aged <60 years or who have an increased risk of thromboembolism.[66][108][151]

Bisphosphonates or denosumab should be considered to maintain or improve bone mineral density and to reduce the risk of fractures in postmenopausal women receiving aromatase inhibitors.[66]

Primary options

tamoxifen: 20 mg orally once daily

anastrozole: 1 mg orally once daily

exemestane: 25 mg orally once daily

lobular carcinoma in situ (LCIS)

without high-risk features

1st line – endocrine therapy (for chemoprevention) and counselling

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1st line –

endocrine therapy (for chemoprevention) and counselling

Treatment for classic LCIS includes endocrine therapy (chemoprevention) and counselling; close monitoring can be considered for patients not desiring chemoprevention.[52]

Patients with LCIS have an increased risk for invasive breast cancer and should be offered chemoprevention.

Endocrine therapy for 5 years is recommended for breast cancer risk reduction for patients aged ≥35 years who have a history of LCIS.[52]

Tamoxifen is indicated for premenopausal women. For postmenopausal women, tamoxifen, raloxifene, anastrozole, or exemestane can be considered.

Tamoxifen and raloxifene have been found to reduce the risk of LCIS progression to invasive breast cancer.[61][62] Anastrozole and exemestane reduce the risk of invasive breast cancer in high-risk postmenopausal women.[154][155]

According to the National Comprehensive Cancer Network (NCCN) breast cancer risk reduction expert panel, tamoxifen is a superior choice of risk reduction agent for most postmenopausal women.[52] However, consideration of adverse effects may lead some patients to choose raloxifene in preference to tamoxifen.[61][62]

Bisphosphonates or denosumab should be considered to maintain or improve bone mineral density and to reduce the risk of fractures in postmenopausal women receiving aromatase inhibitors.[52]

Pleomorphic and florid LCIS should be treated similarly to DCIS.

Those with incidentally found LCIS without high-risk features (e.g., a pathogenic or likely pathogenic genetic mutation conferring a high risk for breast cancer, compelling family history, or prior thoracic radiotherapy at <30 years of age) may opt for endocrine therapy (chemoprevention) and counselling, or close monitoring and counselling.

Primary options

tamoxifen: 20 mg orally once daily

raloxifene: 60 mg orally once daily

anastrozole: 1 mg orally once daily

exemestane: 25 mg orally once daily

1st line – close monitoring and counselling

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1st line –

close monitoring and counselling

Treatment for classic LCIS includes endocrine therapy (chemoprevention) and counselling; close monitoring can be considered for patients not desiring chemoprevention.[52]

If there is concern for progression of LCIS in patients undergoing close monitoring, the management approach may be revised (based on clinical, imaging, and pathology results).

Pleomorphic and florid LCIS should be treated similarly to DCIS.

with high-risk features

1st line – bilateral (prophylactic) mastectomy

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1st line –

bilateral (prophylactic) mastectomy

Bilateral preventive (prophylactic) mastectomy for LCIS may be considered in patients with high-risk features (e.g., those with a pathogenic or likely pathogenic genetic mutation conferring a high risk for breast cancer, compelling family history, or with prior chest wall radiotherapy at age <30 years).[52]

Individualising management of these patients is essential.

Lobular carcinoma, both in situ and invasive, is rare in males.[21]

ONGOING

local recurrence of DCIS

following breast-conserving surgery with adjuvant radiotherapy

1st line – mastectomy ± repeat radiotherapy ± breast reconstruction

Back

1st line –

mastectomy ± repeat radiotherapy ± breast reconstruction

Patients with local recurrence of ductal carcinoma in situ (DCIS) following breast-conserving surgery with adjuvant radiotherapy can be treated with mastectomy followed by repeat radiotherapy, if feasible and indicated.[66]

Adverse effects of radiotherapy are localised to the area(s) through which the radiation passes. The most common acute adverse effects are skin changes (similar to sunburn) and fatigue. The skin may tan, either temporarily or permanently. The irradiated breast may appear smaller due to both surgical and radiotherapy. In patients receiving whole breast radiotherapy (WBRT), a small portion of the lung and ribs receive radiation, which can induce lung scarring and slightly increase the risk of rib fracture. Furthermore, the heart is incidentally exposed to small doses of radiation when treating left-sided breast cancers, which may increase the risk of ischaemic heart disease.[138] Risk of ischaemic heart disease may increase with increasing doses of radiation to the heart.[138]

Hypofractionated and ultra-hypofractionated WBRT regimens minimise the dose and, therefore, sequelae.

Consider – axillary lymph node surgical staging

Back

Consider –

axillary lymph node surgical staging

Additional treatment recommended for SOME patients in selected patient group

Sentinel lymph node biopsy (SLNB) may be considered in patients undergoing mastectomy for local recurrence of DCIS, although there is limited data for repeat SLNB in a patient who had a prior SLNB.[66]

Performing an SLNB after mastectomy is impractical.

The likelihood that an initial diagnosis of DCIS will be upgraded to invasive breast cancer is greater if the disease is high grade, and/or the tumour large (>2.5 cm based on imaging) or palpable.[142][143][144][145][146]

following breast-conserving surgery without adjuvant radiotherapy

1st line – repeat breast-conserving surgery + adjuvant radiotherapy, or mastectomy ± adjuvant radiotherapy

Back

1st line –

repeat breast-conserving surgery + adjuvant radiotherapy, or mastectomy ± adjuvant radiotherapy

Patients with local recurrence of DCIS following breast-conserving surgery without adjuvant radiotherapy can be treated with repeat breast-conserving surgery or mastectomy followed by radiotherapy after repeat breast-conserving surgery or, if indicated, after mastectomy.[66]

Adverse effects of radiotherapy are localised to the area(s) through which the radiation passes. The most common acute adverse effects are skin changes (similar to sunburn) and fatigue. The skin may tan, either temporarily or permanently. The irradiated breast may appear smaller due to both surgical therapy and radiotherapy. In patients receiving whole breast radiotherapy (WBRT), a small portion of the lung and ribs receive radiation, which can induce lung scarring and slightly increase the risk of rib fracture. Furthermore, the heart is incidentally exposed to small doses of radiation when treating left-sided breast cancers, which may increase the risk of ischaemic heart disease.[138] Risk of ischaemic heart disease may increase with increasing doses of radiation to the heart.[138]

Hypofractionated and ultra-hypofractionated WBRT regimens minimise the dose and, therefore, sequelae.

Consider – axillary lymph node surgical staging

Back

Consider –

axillary lymph node surgical staging

Additional treatment recommended for SOME patients in selected patient group

Sentinel lymph node biopsy (SLNB) may be considered in patients undergoing repeat breast-conserving surgery or mastectomy for local recurrence of DCIS, although there is limited data for repeat SLNB in a patient who had a prior SLNB.[66]

Performing an SLNB after mastectomy is impractical.

following mastectomy

1st line – surgical resection ± adjuvant radiotherapy

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1st line –

surgical resection ± adjuvant radiotherapy

Patients with local recurrence of DCIS following mastectomy (with or without adjuvant radiotherapy) can be treated with surgical resection (limited excision) of the local recurrence (if clear margins and acceptable cosmesis can be obtained), followed by radiotherapy (if not previously given) or repeat radiotherapy (if previously given, and if feasible and indicated).[66]

Adverse effects of radiotherapy are localised to the area(s) through which the radiation passes. The most common acute adverse effects are skin changes (similar to sunburn) and fatigue. The skin may tan, either temporarily or permanently. The irradiated breast may appear smaller due to both surgical therapy and radiotherapy. In patients receiving whole breast radiotherapy (WBRT), a small portion of the lung and ribs receive radiation, which can induce lung scarring and slightly increase the risk of rib fracture. Furthermore, the heart is incidentally exposed to small doses of radiation when treating left-sided breast cancers, which may increase the risk of ischaemic heart disease.[138] Risk of ischaemic heart disease may increase with increasing doses of radiation to the heart.[138]

Hypofractionated and ultra-hypofractionated WBRT regimens minimise the dose and, therefore, sequelae.

Consider – axillary lymph node surgical staging

Back

Consider –

axillary lymph node surgical staging

Additional treatment recommended for SOME patients in selected patient group

Sentinel lymph node biopsy (SLNB) may be considered in patients undergoing surgical resection (limited excision) for local recurrence of DCIS, although there is limited data for repeat SLNB in a patient who had a prior SLNB.[66]

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Breast cancer in situ

Treatment algorithm

women with low-risk ductal carcinoma in situ (DCIS)

surgical excision or mastectomy ± breast reconstruction

axillary lymph node surgical staging

adjuvant radiotherapy

adjuvant endocrine therapy

Primary options

women with high-risk DCIS; all men with DCIS

mastectomy ± breast reconstruction

axillary lymph node surgical staging

adjuvant radiotherapy

adjuvant endocrine therapy

Primary options

lobular carcinoma in situ (LCIS)

endocrine therapy (for chemoprevention) and counselling

Primary options

close monitoring and counselling

bilateral (prophylactic) mastectomy

local recurrence of DCIS

mastectomy ± repeat radiotherapy ± breast reconstruction

axillary lymph node surgical staging

repeat breast-conserving surgery + adjuvant radiotherapy, or mastectomy ± adjuvant radiotherapy

axillary lymph node surgical staging

surgical resection ± adjuvant radiotherapy

axillary lymph node surgical staging