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

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 ductal carcinoma in situ (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). 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.[62][74][75]

Guidelines generally recommend breast-conserving therapy as the primary treatment for most patients with low-risk DCIS.[62][76]

The preferred post-surgical margin following breast-conserving therapy for DCIS is ≥2 mm if whole breast radiotherapy is planned.[76][77] If one or more of the post-surgical margins is <2 mm, re-excision or mastectomy is recommended.[78]

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).

Some patients with low-grade DCIS may be considered for lumpectomy alone (e.g., if there are clear margins >1 cm in all directions).[79][80] However, this approach is controversial as most studies show that adjuvant radiotherapy decreases the risk of disease recurrence (local and distant) in various sub-groups of women with DCIS.[81][82] [ ]

Guidelines advise that lumpectomy alone is only appropriate for patients with a low risk of recurrence and following a discussion between the physician and patient on the risks and benefits.[62] If 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.

Sentinel lymph node biopsy (SLNB) should be strongly considered if the patient is undergoing mastectomy, or if tumour excision occurs in an anatomical location making it difficult to perform a future SLNB.[62] Performing an SLNB after mastectomy is impractical. Guidelines do not recommend routine SLNB in women with DCIS who are undergoing breast-conserving surgery.[62][63]

Consider – radiotherapy

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Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

Most patients receive adjuvant whole breast radiotherapy (WBRT) following lumpectomy in order to treat microscopic disease and to reduce the risk of ipsilateral recurrence.[62] Approximately 50% of ipsilateral recurrences are DCIS (i.e., non-invasive) and 50% are invasive.[85]

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.[86][87] Subsequent long-term follow-up from one phase 3 trial supports these findings.[82] Adjuvant radiotherapy has not been demonstrated to improve overall survival in women who underwent breast-conserving surgery for DCIS; the effect of radiotherapy on breast cancer-specific mortality has not been definitively established.[74][87][88][89]

Radiotherapy boost to the tumour bed may be offered along with adjuvant WBRT, depending on individual patient factors and patient preference.[62][76] 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).[90] 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 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.[91]

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.[91]

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.[91] 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; in addition, 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).[91][92]

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.[93][94][95][96][97][98][99] Sub-group analyses of patients with DCIS from two RCTs suggest little difference in recurrence rates up to 10 years.[93][100]

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.[91][99][101][102][103]

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.[94][97][104] Twice-daily EBRT regimens are associated with worse late toxicity and cosmesis.[92][93] APBI/PBI using multicatheter brachytherapy has shown similar late toxicity outcomes to WBRT, with comparable or improved cosmesis.[92][95][98][105]

Radiotherapy delivers local or local and regional therapy, and adverse effects 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.[106] Risk of ischaemic heart disease may increase with increasing doses of radiation to the heart.[106] Newer techniques, such as hypofractionated and ultra-hypofractionated WBRT regimens and APBI/PBI, minimise the dose and, therefore, sequelae.

Consider – endocrine therapy

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Consider –

endocrine therapy

Additional treatment recommended for SOME patients in selected patient group

Most patients with hormone receptor-positive DCIS receive adjuvant endocrine therapy for 5 years to reduce the risk of ipsilateral and/or contralateral invasive breast cancer.

For premenopausal women, tamoxifen 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.[62] Tamoxifen is effective in preventing recurrence in patients with oestrogen receptor-positive breast cancer (both invasive and non-invasive), as well as in decreasing the risk of oestrogen receptor-positive cancers developing in the contralateral breast.[115] [ ]

For postmenopausal women either tamoxifen or an aromatase inhibitor (e.g., anastrozole or exemestane) can be considered as first-line therapy for risk reduction after surgery. Aromatase inhibitors are preferred for women aged <60 years and for those with an increased risk of thromboembolism.[62][76][116] Bisphosphonates or denosumab should be considered to maintain bone mineral density in postmenopausal women receiving aromatase inhibitors.[62]

The efficacy of adjuvant endocrine therapy is independent of age.[117][118] 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.[117]

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 disease, and for males with DCIS.[46]

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).[62][108]

Disease recurrence is low following total mastectomy for DCIS.[109][110]

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

Sentinel lymph node biopsy (SLNB) should be strongly considered in patients undergoing mastectomy.[62] 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.[76][62][111][112][113][114]

Consider – radiotherapy

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Consider –

radiotherapy

Additional treatment recommended for SOME patients in selected patient group

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

Consider – endocrine therapy

Back

Consider –

endocrine therapy

Additional treatment recommended for SOME patients in selected patient group

Most patients with hormone receptor-positive DCIS receive adjuvant endocrine therapy for 5 years to reduce the risk of ipsilateral and/or contralateral invasive breast cancer.

For postmenopausal women either tamoxifen or an aromatase inhibitor (e.g., anastrozole or exemestane) is considered first-line therapy for risk reduction after surgery. Aromatase inhibitors are preferred for women aged <60 years and for those with an increased risk of thromboembolism.[62][76][116] Bisphosphonates or denosumab should be considered to maintain bone mineral density in postmenopausal women receiving aromatase inhibitors.[62]

Primary options

tamoxifen: 20 mg orally once daily

anastrozole: 1 mg orally once daily

exemestane: 25 mg orally once daily

lobular carcinoma in situ

without high-risk features

1st line – observation and counselling

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1st line –

observation and counselling

Treatment for classical LCIS includes observation and counselling. 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 observation and counselling, with or without long-term endocrine therapy (as chemoprevention).

If there is concern about progression of LCIS in patients undergoing observation, the management approach might be revised, based on clinical, imaging and pathology results.

Lobular carcinoma, both in situ and invasive, is rare in males.[13]

Consider – endocrine therapy

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Consider –

endocrine therapy

Additional treatment recommended for SOME patients in selected patient group

Endocrine therapy is recommended for patients aged ≥35 years, and taken for a duration of 5 years.[35] 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.[35][119][120] Anastrozole and exemestane reduce the risk of invasive breast cancer in high-risk postmenopausal women.[35][121][122]

The NCCN advises that tamoxifen is a superior risk-reduction agent for most postmenopausal women.[35] However, consideration of adverse effects may lead some patients to choose raloxifene. Bisphosphonates or denosumab should be considered to maintain bone mineral density in postmenopausal women receiving aromatase inhibitors.[62]

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

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 possibly with prior thoracic radiotherapy at <30 years of age).[35]

Lobular carcinoma, both in situ and invasive, is rare in males.[13]

ONGOING

local recurrence of DCIS

following surgical excision with radiotherapy (breast-conserving therapy, surgical excision with radiotherapy)

1st line – mastectomy ± breast reconstruction

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1st line –

mastectomy ± breast reconstruction

Patients with local recurrence of DCIS following breast-conserving therapy are treated with mastectomy (with or without breast reconstruction).

Reconstruction can be performed at the time of mastectomy (immediate reconstruction) or at 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), if not previously done, should be strongly considered in patients undergoing mastectomy.[62] 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.[62][76][111][112][113][114]

following surgical excision without prior radiotherapy

1st line – re-excision plus radiotherapy

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1st line –

re-excision plus radiotherapy

Re-excision followed by adjuvant radiotherapy is an option in patients who have had surgical excision without prior radiotherapy.

following mastectomy

1st line – re-excision ± adjuvant radiotherapy

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1st line –

re-excision ± adjuvant radiotherapy

Patients with local recurrence of DCIS following mastectomy may undergo re-excision (if clear margins and acceptable cosmesis can be obtained) followed by adjuvant radiotherapy (if not previously given).[62] Repeat radiotherapy may be considered in patients with prior radiotherapy, if feasible.[62]

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Breast cancer in situ

Treatment algorithm

women with low-risk ductal carcinoma in situ

surgical excision or mastectomy ± breast reconstruction

axillary lymph node surgical staging

radiotherapy

endocrine therapy

Primary options

women with high-risk DCIS; all men with DCIS

mastectomy ± breast reconstruction

axillary lymph node surgical staging

radiotherapy

endocrine therapy

Primary options

lobular carcinoma in situ

observation and counselling

endocrine therapy

Primary options

bilateral (prophylactic) mastectomy

local recurrence of DCIS

mastectomy ± breast reconstruction

axillary lymph node surgical staging

re-excision plus radiotherapy

re-excision ± adjuvant radiotherapy