Lori J Pierce, MD
Daniel F Hayes, MD
Anees B Chagpar, MD, MSc, MA, MPH, MBA, FACS, FRCS(C)
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INTRODUCTION — Carcinoma in situ of the breast represents a heterogeneous group of neoplastic lesions confined to the breast ducts (ductal carcinoma in situ [DCIS]) and lobules (lobular carcinoma in situ [LCIS]). The diagnosis of DCIS increased dramatically following the introduction of screening mammography, and now comprises approximately 25 percent of all newly diagnosed breast cancers. The goal of therapy for DCIS is to prevent the development of invasive breast cancer. Therapeutic approaches include surgery, radiation therapy, and adjuvant endocrine therapy.
The treatment of DCIS will be reviewed here. The pathology, epidemiology, and diagnosis of DCIS and microinvasive carcinoma of the breast are presented separately.
●(See "Pathology of breast cancer".)
●(See "Microinvasive breast carcinoma".)
TREATMENT APPROACH — Patients with ductal carcinoma in situ (DCIS) undergo local treatment with mastectomy or breast-conserving therapy (BCT). BCT consists of lumpectomy (also called breast-conserving surgery, wide excision, or partial mastectomy) followed in most cases by adjuvant radiation. Radiation therapy may be reasonably omitted in a select population of patients with low-risk disease. (See 'Local treatment' below and 'Omission of RT for low-risk disease' below.)
A sentinel lymph node biopsy can be avoided in most women. However, it should be obtained in women with high-risk features for whom resection (mastectomy or BCT) may compromise the ability to perform a future sentinel lymph node biopsy. (See 'Indications for SLNB' below.)
Following local treatment, the decision to administer endocrine therapy to reduce the risk of subsequent cancers depends upon the choice of local therapy and the tumor hormone receptor status (see 'Endocrine therapy' below):
●BCT or unilateral mastectomy; estrogen/progesterone receptor (ER/PR) positive – We offer five years of endocrine therapy for risk reduction, with choice of therapy dependent on the patient’s menopausal status. Tamoxifen is used for premenopausal women. For postmenopausal women, either tamoxifen or anastrazole are acceptable options.
●BCT or unilateral mastectomy; ER/PR negative – While the benefit is less clear and we do not routinely utilize tamoxifen in this setting, some women may prefer to take adjuvant tamoxifen to prevent a new ER-/PR-positive contralateral or ipsilateral breast cancer.
●Bilateral mastectomy – For women who have undergone bilateral mastectomy, there is no role for adjuvant endocrine therapy.
Posttreatment surveillance consists of regular history and physical examination and mammography (if applicable), without routine utilization of laboratory tests, tumor markers, or other imaging. (See 'Posttreatment surveillance' below.)
LOCAL TREATMENT — Ductal carcinoma in situ (DCIS) of the breast represents a broad biologic spectrum of disease. The best form of local therapy is debated.
Local treatment for DCIS involves mastectomy or breast-conserving therapy (BCT), which consists of lumpectomy (also called wide excision or partial mastectomy) followed in most cases by adjuvant radiation therapy (RT). In some instances, sentinel lymph node biopsy may also be performed.
Mastectomy versus breast-conserving therapy — Both mastectomy and BCT are reasonable options for most women with DCIS, although not all women will meet the criteria for BCT. A choice between these is a personal one and should be made after discussion between patient and provider. (See 'Criteria for BCT' below.)
Patients found to have invasive or microinvasive disease at surgery should be managed accordingly. (See "Overview of the treatment of newly diagnosed, non-metastatic breast cancer" and "Microinvasive breast carcinoma".)
Relative efficacy — Although mastectomy achieves excellent long-term survival with a local recurrence rate on the order of 1 percent, it provides overly aggressive treatment for many women. BCT has less morbidity but is associated with a higher risk of local recurrence [1-8].
In a 2015 observational study that included over 100,000 patients who received a diagnosis of DCIS in the Surveillance, Epidemiology, and End Results (SEER) database, when compared with lumpectomy (with or without radiotherapy), mastectomy resulted in :
●A similar 10-year breast cancer-specific mortality (multivariate hazard ratio [HR] for mastectomy versus lumpectomy 1.2, 95% CI 0.96-1.50)
●Lower rates of ipsilateral invasive recurrence (1.3 versus 3.3 percent)
While this study did not report on morbidity associated with each surgery, information regarding the relative safety of each surgery comes from data of early breast cancer, which suggest that while postoperative complication rates associated with either surgery are low, they are more frequent with mastectomy . Postoperative morbidities associated with mastectomy and BCT are discussed in more detail separately. (See "Mastectomy: Indications, types, and concurrent axillary lymph node management", section on 'Complications' and "Breast conserving therapy", section on 'Postoperative Complications'.)
Together these data suggest that BCT for DCIS offers a low rate of recurrence with minimal complications. However, mastectomy is a reasonable alternative for women who wish to take all possible measures to minimize risk of recurrence.
Criteria for BCT — Women with DCIS are candidates for BCT as long as the following criteria are met:
●The lesion should be limited to one quadrant or section of the breast. Multifocal disease is not necessarily a contraindication to BCT .
●Cosmetically acceptable resection is achievable given the size of disease relative to size of the breast.
●Histologically negative margins are able to be achieved with lumpectomy. Negative margins are defined by tumor-filled ducts separated by a measurable distance from the inked surface. We recognize it may not be possible to obtain wide margin widths (ie, 10 mm), particularly with DCIS close to the skin or muscle. For women who will be treated with postoperative RT, a lesser margin is adequate. If the area of concern is close to the fascia, the dissection should be carried down to and include resection of the pectoral fascia [11-13]. (See 'Margin width' below.)
Patients whose disease does not fit the above criteria should proceed with mastectomy.
Efficacy — Mastectomy is curative for over 98 percent of patients with DCIS [14-18]. Disease recurrence is rare after mastectomy (1 to 2 percent) [3,19-21]. Post-mastectomy recurrences may be the result of unrecognized invasive carcinoma, inadequate margins, or incomplete removal of breast tissue at the time of mastectomy. (See 'Margin width' below.)
Women treated with mastectomy are candidates for breast reconstruction; immediate reconstruction is usually preferred. (See "Overview of breast reconstruction".)
Patients undergoing mastectomy for DCIS may benefit from sentinel lymph node biopsy. (See 'Indications for SLNB' below.)
Women with unilateral DCIS are at a modestly increased risk of developing either invasive breast cancer or DCIS in the contralateral breast [3,19]. Therefore, some women with DCIS choose contralateral prophylactic mastectomy to prevent a future breast cancer in the contralateral breast , despite a lack of a proven survival benefit. Alternatively, women who have undergone unilateral mastectomy for DCIS may elect to take endocrine therapy as chemoprevention against a future breast cancer. For women who have undergone bilateral mastectomy, there is no role for adjuvant endocrine therapy. (See "Contralateral prophylactic mastectomy" and 'Endocrine therapy' below.)
Postmastectomy RT is not routinely indicated for DCIS unless extensively positive margins are discovered upon pathologic review of the surgical specimen. (See 'Margin width' below.)
Indications for SLNB — While sentinel lymph node biopsy (SLNB) is not indicated for most patients with DCIS, SLNB should be obtained for women requiring mastectomy (ie, those who do not meet criteria for BCT). (See 'Criteria for BCT' above.)
After a total mastectomy, the lymphatic drainage pattern will be permanently altered, making it impossible to accurately perform SLNB at a later date if invasive cancer is found unexpectedly in the mastectomy specimen. Patients who require a mastectomy have a higher likelihood of harboring an invasive cancer compared with women with a smaller focus of disease and therefore should undergo an SLNB at the time of surgery .
By contrast, our practice is not routinely to pursue SLNB in patients who are candidates for BCT who instead opt for mastectomy, given that the likelihood of invasive cancer in such patients is low. We recognize, however, that practice patterns vary, and others may reasonably choose to perform SLNB routinely for all patients undergoing mastectomy for DCIS.
Breast-conserving therapy — BCT for DCIS refers to lumpectomy to remove the tumor with negative surgical margins, generally followed by RT to eradicate any residual disease [1,3-8,10-13].
Surgical resection — The goal of BCT for DCIS is complete resection with negative margins in a cosmetically acceptable manner. When DCIS is present on a core biopsy, needle or wire localization under mammographic guidance prior to BCT may ensure complete resection. For larger areas of suspicious microcalcifications, bracketing of the area maximizes the likelihood of a complete excision with adequate margins on the first attempt, thereby diminishing the need for re-excision [23,24]. (See 'Margin width' below.)
For patients whose disease is associated with suspicious calcifications on preoperative mammography or in whom the adequacy of the margins is in question, a post-excision mammogram should be obtained prior to initiation of radiation. Residual suspicious calcifications warrant a wire-localized approach to re-excision or a boost of radiation to the postsurgical site [25-27]. (See "Diagnostic evaluation of women with suspected breast cancer", section on 'Mammographic features of breast cancer'.)
Radiation therapy — RT is the standard for patients treated with BCT, though it may be reasonable to omit in selected patients with advanced age, extensive comorbidities, or small foci of low-grade disease resected with negative margins. (See 'Omission of RT for low-risk disease' below.)
RT after lumpectomy reduces the risk of local invasive and noninvasive recurrences. As described below, randomized trials have shown that adjuvant RT significantly reduces the risk of in-breast tumor recurrence by 50 percent or greater compared with excision alone. However, treating all women who undergo breast-conserving surgery for DCIS with adjuvant RT may be overtreatment for some [28,29]. The majority of cases of DCIS do not recur when treated with excision alone, and there may be subgroups of patients with DCIS in whom the risk of local recurrence is so low that RT may be of no benefit. The difficulty, however, is in reliably predicting those patients who would not recur in the absence of RT. (See 'Omission of RT for low-risk disease' below.)
Benefits of treatment — RT significantly reduces the odds of in-breast recurrence but does not change the odds of distant recurrence or mortality, and therefore should be discussed with each patient carefully. The benefit of RT for DCIS was shown in a 2009 meta-analysis of RT compared with no further treatment following lumpectomy . Compared with lumpectomy alone, RT resulted in a reduction in the risk of all ipsilateral breast events (pooled hazard ratio [HR] 0.49, 95% CI 0.41-0.58). This translated into a number needed to treat of nine women to prevent one ipsilateral breast recurrence.
In addition, the risk reduction for local recurrence associated with RT appears to be long-lasting, though this is not associated with a survival advantage. This was shown in a report of the long-term follow-up of the National Surgical Breast and Bowel Project Trial B-17 . At 15 years, compared with excision alone, RT resulted in:
●A lower rate of ipsilateral invasive recurrence (8.9 versus 19.4 percent)
●Similar overall survival (83 versus 84 percent) and cumulative all-cause mortality rate through 15 years (HR for death 1.08, 95% CI 0.79-1.48, 17.1 versus 15.8 percent)
Similar findings were reported from a large observational study of the Surveillance, Epidemiology, and End Results (SEER) database that included over 100,000 patients with DCIS. A subgroup of 60,000 women were treated with BCT, with or without radiation . Compared with lumpectomy alone, the addition of radiation was associated at 10 years with:
●A lower rate of ipsilateral breast cancer recurrence (2.5 versus 4.9 percent in the lumpectomy alone group)
●Similar breast cancer-specific mortality (0.8 versus 0.9 percent, HR 0.86, CI 0.67-1.10).
RT schedule — As in the treatment of invasive breast cancer, the standard of care for patients undergoing BCT is to deliver adjuvant whole-breast RT (WBRT). Conventionally dosed WBRT is delivered to the entire breast in 1.8 to 2 Gy daily fractions over 4.5 to 5 weeks to a total dose of 45 to 50 Gy. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)
Alternative approaches, such as the use of rapid fractionation schedules or accelerated partial-breast RT, are under investigation and early results are promising [31-33]. Further evaluation of these techniques is required before they can be considered an alternative to WBRT for DCIS.
In two single-institution trials that enrolled a total of 145 women who had undergone breast-conserving surgery for DCIS, patients received accelerated partial-breast RT (41 to 42 Gy delivered over 15 fractions) . In a combined analysis, the recurrence rate at five years was 4 percent, which was similar to the rate of recurrence following WBRT reported in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 trial (range, 3 to 8 percent for non-invasive and invasive recurrences, respectively) . (See "Radiation therapy techniques for newly diagnosed, non-metastatic breast cancer".)
Omission of RT for low-risk disease — As described above, RT reduces the odds of in-breast recurrence but does not change the odds of distant recurrence or decrease mortality. For patients with low-risk disease that has been fully resected with widely negative margins, the absolute reduction of in-breast recurrence may not be large enough to justify the risks associated with RT. In such patients, it is reasonable to omit RT, especially in the setting of comorbidity, advanced age, or patient preference. We have a higher threshold to omit radiation for young women given some data suggesting RT is more likely to benefit these patients .
While the results from the NSABP B-17 trial described above have been used to argue for RT in all women who undergo lumpectomy for pure DCIS, methodologic issues such as suboptimal pathologic evaluation and uncertainty about the completeness of excision may have led to an overestimation of the benefit of RT in this study. Moreover, RT is expensive, time consuming, and may be accompanied by significant side effects, and so omission for patients likely to derive the least benefit is reasonable. (See "Radiation therapy techniques for newly diagnosed, non-metastatic breast cancer".)
Since RT reduces the risk of ipsilateral recurrence without changing the risk of developing contralateral disease, omission of RT would be a reasonable approach for patients with an ipsilateral recurrence risk approximately equal to the risk of developing contralateral disease. Among women diagnosed with DCIS, the risk of developing a contralateral breast cancer or DCIS is approximately 3 to 10 percent [36-38]. As described below, studies have tried to identify such a low-risk population using histopathologic and gene expression analysis. While it is difficult to identify a clear cut low-risk population, the benefit of RT becomes less clear as the risk of ipsilateral recurrence approaches that of contralateral recurrence.
Histopathologic criteria — While there are no strict criteria for "low risk," our approach has been to define low risk as DCIS that is low- or intermediate-grade, small (<2.5 cm in size), and resected with widely negative margins (≥1 cm). (This negative margin cutoff is more conservative than that used in the studies described below.) Omission of RT in such patients is reasonable, although associated with a small risk of ipsilateral recurrence.
Several studies suggest that clinical pathologic criteria may define a low-risk cohort of patients with DCIS for whom RT may be reasonably omitted given a low risk of recurrence. These studies are summarized below.
The Eastern Cooperative Oncology Group (E5194) was an observational study that investigated excision without RT in women with low- to intermediate-grade versus high-grade DCIS [39,40]. Eligible patients had <2.5 cm of low- to intermediate-grade DCIS or <1.0 cm for high-grade DCIS. Margins ≥3 mm were required and a negative post-excision mammogram was obtained for all participants. Tamoxifen following excision was allowed but not mandated. With a median follow-up of 6.7 years, the following local recurrent rates (LRR) were reported:
●Five-year LRR for low- or intermediate-grade DCIS (n = 565) was 6.1 percent (95% CI 4.1-8.2).
●Five-year LRR for high-grade DCIS (n = 105) was 15.3 percent (95% CI 8.2-22.5).
●The 12-year LRRs for the low- or intermediate-grade group versus the high-grade group were 14.4 and 24.6 percent, respectively.
These results suggest that patients with low- to intermediate-grade DCIS may be better candidates for local excision alone than those with high-grade lesions, who have a higher risk of recurrence. However, a 10-year LRR approaching 15 percent in patients with low- or intermediate-grade DCIS may not be low enough to justify the routine omission of post-excision RT even in this patient population. This 10-year rate of LRR occurred despite a median tumor size of only 6 mm.
The Radiation Therapy Oncology Group (RTOG) 9804 trial, which was closed early due to low accrual, investigated outcomes of RT omission in the setting of low-risk DCIS, randomizing 636 patients with low-risk disease to either RT or observation after surgery . In this study, low risk consisted of low- or intermediate-grade DCIS measuring <2.5 cm with resection to negative margins of ≥3 mm. Median tumor size was 5 mm. While recurrence rates were decreased with RT, the recurrence rate was also low in the control group. With a median follow-up of seven years, RT resulted in:
●A reduced risk of a local recurrence compared with observation (HR 0.11, 95% CI 0.03-0.47). As noted, however, few women in either group experienced a recurrence during follow-up, with local recurrence rates of 0.9 and 6.7 percent, respectively.
●A higher rate of mild to moderate (grade 1 or 2) toxicities (76 versus 30 percent), although the rate of serious toxicities was similar in both arms (4 percent). Of patients treated with RT, grade 1, 2, or 3 late toxicities were seen in 30, 5, and 0.7 percent.
●No difference in either disease-free survival (DFS) or overall survival (OS).
In 2016, a retrospective study of approximately 32,000 patients in the Surveillance, Epidemiology, and End Results (SEER) database who were treated with BCT for DCIS found that adjuvant radiation was associated with improved survival for patients with high nuclear grade, younger age, or larger tumor size . Radiation was not associated with a breast cancer survival benefit when these factors were absent. While this study used cutoffs of <60 for younger age and >1.6 cm for larger tumor size, it is likely that risk occurs on a continuum for these factors.
Identifying patients who can safely be managed with surgical excision using clinicopathologic data remains a challenge, and some patients may value the reduction in recurrence (DCIS and invasive) enough to warrant pursuing post-excision RT regardless of their risk factors.
Gene expression analysis — Gene expression analysis such as the Oncotype DX DCIS recurrence score [42,43] has been studied as a tool for identification of patients for whom post-lumpectomy RT may reasonably be omitted, but data regarding its utility are still preliminary. Although gene expression analyses in DCIS patients are not routine, if a DCIS recurrence score has already been obtained, it should be considered within the context of known prognostic factors (ie, tumor size, grade, and margin width) as well as radiation-related factors (ie, cost, convenience, and possible side effects) in consideration for omission of RT after lumpectomy.
The DCIS recurrence score utilizes a multigene assay that was prospectively evaluated in 327 patients with DCIS who participated in the above mentioned E5194 trial. (See 'Omission of RT for low-risk disease' above.)
In a preliminary analysis, patients were stratified by recurrence score into three groups that were associated with the following risks of an ipsilateral breast event (DCIS or invasive breast cancer) :
●Low (<39) – 12 percent
●Intermediate (39 to 54) – 25 percent
●High (≥55) – 27 percent
Similar results were found in a large study presented at the 2014 San Antonio Breast Cancer Symposium . This study included over 1500 patients with DCIS who were treated with breast-conserving surgery, with or without radiation. At a median follow-up of 9.4 years, the 10-year rate of developing a local recurrence, stratified by recurrence score, in patients treated with surgery versus surgery and radiation was as follows:
●Low-risk – 12.7 percent and 7.5 percent, respectively
●Intermediate-risk – 33.0 and 13.6 percent, respectively
●High-risk – 27.8 and 20.5 percent, respectively
These results demonstrate that patients with a low DCIS recurrence score have a lower risk of in-breast recurrence than those with intermediate or high DCIS scores and may derive a lesser benefit from radiation. However, the risk of ipsilateral recurrence in those in the low-risk group who did not undergo surgery was still higher than the expected rate of contralateral breast disease. Further validation of these results is required before the multigene assay can become a part of clinical practice.
SLNB not routinely indicated with BCT — SLNB is not indicated for most patients undergoing BCT for DCIS. Omitting SLNB at the time of breast-conserving surgery for DCIS decreases perioperative morbidity [44-46]. Because DCIS is a preinvasive lesion, axillary nodes are rarely positive in DCIS, even in cases of extensive multifocal high-grade disease [22,47-53]. In one retrospective review, none of 297 patients with a final diagnosis of DCIS had a positive SLNB .
If invasive breast cancer is identified after a breast-conserving surgery is performed for DCIS, SLNB can be performed as a second procedure. Invasive carcinoma has been reported in 10 to 20 percent of excision specimens following a biopsy diagnosis of DCIS . Disease stage and subsequent axillary management may change for such patients based on the new stage of the breast cancer [45,46]. (See "Tumor, Node, Metastasis (TNM) staging classification for breast cancer" and "Microinvasive breast carcinoma" and "Overview of the treatment of newly diagnosed, non-metastatic breast cancer".)
Pathologic examination — For patients with DCIS, complete tissue processing is essential to exclude small foci of invasive carcinoma, determine the size and/or extent of DCIS, ascertain the presence of contiguous or multifocal distribution, and evaluate the distance to the resection margins (margin width) [55-57].
Key pathologic components — The pathology report should include the following:
●Nuclear grade (ie, low, intermediate, or high).
●The size or extent of the lesion.
●The distance to the closest margin, including whether the margins were only focally or extensively involved [58,59].
●Specimen orientation to identify specific margins and allow for targeted re-excision if necessary.
The role of human epidermal growth factor receptor 2 (HER2) expression in DCIS is evolving. However, at present, consensus guidelines do not recommend routine testing of pure DCIS for HER2 overexpression [60,62]. (See "HER2 and predicting response to therapy in breast cancer", section on 'Clinical utility of HER2 testing'.)
The pathology of DCIS is discussed separately. (See "Pathology of breast cancer".)
Margin width — The margin width (distance between the edge of the DCIS and the inked margins) reflects the completeness of excision and is an important determinant of local recurrence in DCIS, particularly for patients considering foregoing radiotherapy after breast-conserving surgery . Our approach is to consider margins ≥2 mm as negative, <2 mm as close, and involvement of the inked surface as positive, consistent with results of a meta-analysis described below as well as national guidelines [64-66]. However, the volume/extent of DCIS, its distribution throughout a specimen, the volume of the excision, and the volume of DCIS deemed close to the margin (focal or extensive) may influence determinations of what constitutes a sufficient margin. Re-excision(s) and/or radiation boost should be performed if close or positive margins are present. If the close or positive margins are extensive, mastectomy may be indicated.
Data regarding appropriate margin width for patients treated for DCIS have been conflicting. A meta-analysis of 22 trials enrolling 4660 patients treated with BCT and RT found a 64 percent reduction in local recurrence risk in patients with a negative margin after BCT compared with patients with a positive margin (odds ratio [OR] 0.36, 95% CI 0.27-0.47). In examination of specific margin thresholds, a 2 mm or larger margin was associated with fewer local recurrences compared with margins smaller than 2 mm (OR 0.53, 95% CI 0.26-0.96) . By contrast, a retrospective analysis of almost 1100 patients suggested that margins smaller than 2 mm were not associated with increased rate of local recurrences compared with margins larger than 2 mm . In light of these conflicting data, we utilize the more conservative threshold of smaller than 2 mm as an indication for further intervention.
SYSTEMIC TREATMENT — The primary role of systemic treatment is to reduce the risk of invasive breast cancer in the ipsilateral or contralateral breast. Chemotherapy plays no role in the management of these patients given the low risk of distant metastatic disease and overall good prognosis.
Endocrine therapy is offered to the majority of patients with hormone receptor-positive ductal carcinoma in situ (DCIS). (See 'Indications' below.)
There is no current indication for human epidermal growth factor receptor 2 (HER2)-directed therapy in the management of DCIS. (See 'HER2-directed therapy' below.)
Endocrine therapy — Approximately 50 to 75 percent of DCIS lesions express estrogen receptors (ER) and/or progesterone receptors (PR) [68-70]. Of the endocrine agents approved for use as adjuvant therapy for invasive breast cancer, only tamoxifen is approved in the United States to prevent invasive breast cancer recurrences in women with DCIS, although data reviewed below indicate that the aromatase inhibitor anastrozole is also an acceptable option. (See 'Aromatase inhibitors' below.)
Indications — Following local treatment, the decision to administer endocrine therapy to reduce the risk of subsequent cancers depends upon the tumor hormone receptor status and the choice of local therapy:
●For women with ER-positive DCIS who have not undergone a bilateral mastectomy, we suggest endocrine therapy rather than observation, and both tamoxifen and the aromatase inhibitor anastrazole are reasonable. Endocrine therapy reduces recurrence rates, but has not been shown to improve survival. The data to support this recommendation are discussed below. (See 'Tamoxifen' below and 'Aromatase inhibitors' below.)
●We do not routinely utilize tamoxifen as chemoprevention for women with ER-negative DCIS given that the benefit of endocrine therapy does not reduce the risk of recurrence in this population. Some women may opt to take tamoxifen, however, to decrease the risk of developing a new endocrine receptor-positive DCIS or breast cancer. (See 'Tamoxifen' below.)
●In women having bilateral mastectomies for DCIS, the risks of adverse effects from tamoxifen outweigh any potential benefit for risk reduction.
Tamoxifen — For women with ER-positive DCIS treated with breast-conserving therapy (BCT), we offer postoperative tamoxifen treatment for five years to prevent ipsilateral recurrences and new events, both in the ipsilateral and contralateral breast. The risks of side effects, including endometrial cancer and thromboembolic events, while small, need to be discussed with the patient. (See "Managing the side effects of tamoxifen".)
For women treated with BCT, multiple trials have demonstrated that postoperative tamoxifen is more effective than placebo in reducing the risk of invasive breast cancer, with or without adjuvant radiotherapy, although there is no apparent benefit for survival [7,36,71,72]. This was illustrated in a meta-analysis of two randomized trials, National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 and United Kingdom, Australia, and New Zealand DCIS (UK/ANZ DCIS), that together included 3375 patients :
●The addition of tamoxifen to BCT for DCIS reduced the recurrence risk of ipsilateral DCIS (hazard ratio [HR] 0.75, 95% CI 0.61-0.92) and contralateral DCIS (relative risk [RR] 0.50, 95% CI 0.28-0.87).
●There was a trend towards a lower risk of ipsilateral invasive carcinoma (HR 0.79, 95% CI 0.61-1.01) that did not reach statistical significance and a lower risk for contralateral invasive carcinoma (RR 0.57, 95% CI 0.39-0.83).
●There was no benefit of tamoxifen in all-cause mortality (RR 1.11, 95% CI 0.89-1.39).
The benefit of postoperative tamoxifen is primarily in patients with ER-positive DCIS. The ability of ER status to predict response to tamoxifen for women with DCIS was addressed in a retrospective review of data from the NSABP B-24 trial that included 41 percent of the original cohort (732 patients) . At 10 years of follow-up, patients with ER-positive DCIS treated with tamoxifen had significant decreases in any subsequent (invasive and/or noninvasive; ipsilateral and/or contralateral) breast cancer events compared with patients receiving placebo (HR 0.58, 95% CI 0.42-0.81). No significant benefit was observed in ER-negative DCIS.
Aromatase inhibitors — The aromatase inhibitor anastrozole is a reasonable alternative to tamoxifen in postmenopausal women with ER-positive DCIS. Toxicities associated with aromatase inhibitors include loss of bone density, fractures, and cardiovascular risk and should be discussed with the patient. Side effects of aromatase inhibition is discussed in detail elsewhere. (See "Adjuvant endocrine therapy for non-metastatic, hormone receptor-positive breast cancer", section on 'Side effects' and "Evaluation and management of aromatase inhibitor-induced bone loss".)
The NRG Oncology/NSABP B-35 trial, which enrolled over 3100 postmenopausal women with hormone receptor-positive DCIS who underwent BCT, demonstrated that anastrazole resulted in a decreased rate of breast cancer events at 10 years compared with tamoxifen . Patients were randomly assigned to treatment with tamoxifen or anastrozole for five years. At a median follow-up of nine years, when compared with tamoxifen, anastrozole resulted in:
●A lower incidence of subsequent breast cancer events (ie, recurrent DCIS or subsequent invasive breast cancer) (90 versus 122 events, respectively; HR 0.73), including a lower rate of invasive breast cancer (43 versus 69 cases; HR 0.62).
●Improved estimated breast cancer-free survival at 10 years (93.1 versus 89.1 percent).
●No significant difference in either disease-free survival (DFS, 235 versus 260 events; HR 0.89, 95% CI 0.75-1.07) or overall survival (OS, 98 versus 88 deaths; HR 1.11, 95% CI 0.83-1.48). The estimated 10-year OS was approximately 92 percent for both groups.
The analysis also suggested that these benefits of anastrozole were mostly seen in women under age 60 years. These results support the use of anastrozole in postmenopausal women with DCIS. However, this study also confirms the overall good prognosis for women with DCIS. Therefore, decisions on whether anastrozole is indicated should be individualized based on the patient and her tumor characteristics.
HER2-directed therapy — Current data are not sufficient to support use of HER2-directed therapy in DCIS. We do not recommend HER2 testing of DCIS, in concordance with American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines .
Compared with invasive breast cancer, DCIS more often expresses HER2. As an example, in a study of 708 malignant ductal lesions (59 with DCIS, 649 with invasive disease), the proportion that were HER2-positive was 56 and 15 percent, respectively .
However, HER2 overexpression does not affect the management strategy of DCIS. Limited data demonstrate an immunologic response to a single dose of trastuzumab in patients with HER2-positive DCIS, though changes in other histologic markers were not noted . The NSABP B-43 study will evaluate the effect of administering two doses of trastuzumab concurrent with radiation therapy for women who underwent a partial mastectomy for DCIS [78,79].
POSTTREATMENT SURVEILLANCE — The goals of surveillance after treatment for ductal carcinoma in situ (DCIS) are early recognition and treatment of potentially curable disease recurrences and second primary breast cancers, evaluation for therapy-related complications, and detection of symptoms consistent with metastatic disease. As with invasive disease, history and physical examination and routine mammography (if applicable) form the cornerstone of posttreatment surveillance (table 1). Other types of imaging, laboratory tests, and tumor markers should not be routinely obtained. (See "Approach to the patient following treatment for breast cancer".)
APPROACH TO RECURRENT DISEASE — Approximately one-half of all local-regional recurrences are invasive, regardless of treatment approach [4,80,81]. If the recurrence included any invasive disease, it should be treated in a manner appropriate for newly diagnosed invasive breast cancer. (See "Overview of the treatment of newly diagnosed, non-metastatic breast cancer".)
Locoregional treatment — The treatment for a patient with recurrent ductal carcinoma in situ (DCIS) is based upon disease extent, location, and the prior surgical approach (ie, mastectomy versus lumpectomy):
●For patients treated with breast-conserving therapy (BCT) (ie, prior wide local excision plus radiation therapy [RT]), we would perform a mastectomy rather than breast-conserving surgery because these patients are not candidates for further RT.
●For patients treated with breast-conserving surgery who did not undergo previous RT, options include repeat excision plus RT or mastectomy. A choice between them depends on the patient, extent of disease, and provider preferences.
●Although rare, patients who underwent a mastectomy may experience a recurrence in the mastectomy flap. For these patients, we perform excision of the area. These patients should also meet with a radiation oncologist to discuss the role of post-excision RT. (See "Management of locoregional recurrence of breast cancer after mastectomy".)
●For patients with an invasive local recurrence after treatment for DCIS, we perform a metastatic work-up. The management of these patients is discussed separately. (See "Management of locoregional recurrence of breast cancer after breast conserving therapy", section on 'Staging workup'.)
Endocrine therapy — Endocrine therapy should be offered as chemoprevention to women with recurrent DCIS who did not previously receive it. (See 'Tamoxifen' above.)
For women who were on tamoxifen and experienced a recurrence of pure DCIS, the benefit of continued tamoxifen following locoregional treatment for recurrent disease is not clear. While some experts prefer to discontinue tamoxifen in these patients, others may prefer to switch to a different endocrine therapy (especially in postmenopausal women) or to continue tamoxifen. In the absence of data to inform a preferred option, the role of endocrine therapy as chemoprevention (for women who experience a recurrence of DCIS while on tamoxifen) should be discussed with their clinician.
PROGNOSIS — With appropriate treatment, the prognosis for patients with ductal carcinoma in situ (DCIS) is excellent. Advancements in screening for DCIS (allowing for early detection, prior to acquisition of high-risk features, and facilitating complete excision), more rigorous and standardized pathologic review of margins, and adjuvant endocrine therapy have improved outcomes .
In an analysis of over 100,000 patients with DCIS enrolled in the Surveillance, Epidemiology, and End Results (SEER) database, the 20-year breast cancer mortality among women with DCIS was 3.3 percent . The risk of ipsilateral invasive recurrence at 20 years was 5.9 percent, and the risk of contralateral invasive recurrence was 6.2 percent. In this study, predictors of a higher risk of death from breast cancer included young age at diagnosis (before age 35 years, hazard ratio [HR] 2.3, 95% CI 1.6-3.2), high grade (HR 1.88, 95% CI 1.38-2.55), and black ethnicity (HR 2.55, 95% CI 2.17-3.01) (figure 1). Estrogen receptor (ER) positivity predicted a lower risk of death (HR 0.53, 95% CI 0.41-0.69) (figure 2).
A separate, prospective, observational study also suggested that risk of recurrence of DCIS decreased with age. Among 2996 patients with DCIS, the HRs for recurrence were as follows, with age <40 years as a reference: for patients age 40 to 49 years, 0.82; 50 to 59 years, 0.46; 60 to 69 years, 0.50; 70 to 79 years, 0.56; and 80 years or greater, 0.21 . This association persisted for cohorts treated either with or without radiation. Ten-year invasive recurrence was 16 percent among those under 40 years versus 6.5 percent for those ≥40 years.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topics (see "Patient education: Ductal carcinoma in situ (DCIS) (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Ductal carcinoma in situ (DCIS) of the breast represents a heterogeneous group of neoplastic lesions confined to the breast ducts and lobules. The goal of therapy for DCIS is to prevent the development of invasive breast cancer. Therapeutic approaches include surgery, radiation therapy (RT), and adjuvant endocrine therapy. (See 'Introduction' above.)
●Local therapy for DCIS consists of mastectomy or breast-conserving therapy (BCT). BCT for DCIS includes lumpectomy, generally followed by RT, and results in breast cancer-specific survival rates comparable to mastectomy, although the rate of local recurrence is higher with BCT.
●Candidates for BCT include patients with DCIS whose disease is localized to one quadrant and can be resected with negative margins in a cosmetically acceptable manner, taking into account the size of disease relative to the breast size. Re-excision(s), mastectomy, or radiation boost should be performed if close or positive margins are present. (See 'Breast-conserving therapy' above.)
●For patients who are candidates for BCT, we suggest BCT over mastectomy (Grade 2B). We recommend that most women undergoing BCT receive RT in addition to lumpectomy (Grade 1B). (See 'Breast-conserving therapy' above.)
●For patients with very small foci of low-grade DCIS, breast-conserving surgery only (ie, omission of RT) with widely negative margins (ideally 10 mm) is an option. However, prospective randomized evidence to support the omission of adjuvant radiation is limited, even in selected low-risk cases. (See 'Radiation therapy' above.)
●For most patients with DCIS, we recommend not performing surgical evaluation of the axilla (Grade 1A). However, we suggest sentinel lymph node biopsy (SLNB) in patients who do not meet criteria for BCT and thus require mastectomy (Grade 2B). (See 'Indications for SLNB' above.)
●For women with estrogen receptor (ER)-positive DCIS treated with breast-conserving surgery with or without RT, we suggest endocrine therapy rather than observation (Grade 2B). For women who opt for treatment, the choice between anastrozole and tamoxifen should be individualized based on the side effect profile of each medication, menopausal status, and the preferences of the patient. (See 'Systemic treatment' above.)
●In general, for women who underwent unilateral mastectomy for ER-positive DCIS, we suggest endocrine therapy rather than observation (Grade 2C). For these patients, the use of endocrine therapy should be considered "chemoprevention" and not treatment to prevent recurrence for this diagnosis. In other words, it would be given with the intent to prevent a new primary contralateral or ipsilateral breast cancer. (See 'Systemic treatment' above.)
●We do not routinely utilize tamoxifen as chemoprevention for women with ER-negative DCIS given that the benefit of endocrine therapy does not reduce the risk of recurrence in this population. Some women may opt to take tamoxifen, however, to decrease the risk of developing a new endocrine receptor-positive DCIS or breast cancer. (See 'Tamoxifen' above.)
●The treatment for a patient diagnosed with a recurrence following original treatment for DCIS is based upon whether the disease is purely in situ or has an invasive component, the disease extent, location, prior surgical approach (ie, mastectomy versus lumpectomy), and whether RT or endocrine therapy was previously administered. (See 'Approach to recurrent disease' above.)
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