Breast-conserving therapy

INTRODUCTION — Breast-conserving therapy (BCT) refers to breast-conserving surgery (BCS; ie, lumpectomy) typically followed by radiation therapy (RT) to eradicate any microscopic residual disease. It is an alternative to mastectomy for patients with early breast cancer.

Prior to the advent of BCT, all breast cancers were treated with mastectomy. Despite the fact that modern surgical techniques are less morbid than radical mastectomy, a mastectomy still requires the loss of the breast. The goals of BCT are to provide the survival equivalent of mastectomy, a cosmetically acceptable breast, and a low rate of recurrence in the treated breast.

The indications, techniques, complications, and outcomes of BCT will be reviewed here. BCT requires adjuvant radiation therapy in most patients, which is discussed in detail elsewhere. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

Additional topics related to the diagnosis and management of breast cancer include:

●(See "Clinical features, diagnosis, and staging of newly diagnosed breast cancer".)

●(See "Diagnostic evaluation of suspected breast cancer".)

●(See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer".)

●(See "Overview of sentinel lymph node biopsy in breast cancer".)

●(See "Mastectomy".)

●(See "Surgery and radiation for locoregional recurrences of breast cancer".)

PATIENT SELECTION FOR BCT — Although breast-conserving therapy (BCT) provides an acceptable alternative to mastectomy for the treatment of invasive breast cancer, it is not applicable to all patients. The selection of appropriate patients is crucial to the success of BCT. Most contraindications to BCT are due to either a failure to obtain margin control with breast-conserving surgery (BCS) or an inability to tolerate adjuvant radiotherapy.

Absolute contraindications for BCT

●A clinical diagnosis of inflammatory breast cancer (IBC) or the presence of extensive skin changes or dermal lymphatic involvement consistent with IBC. Even following a complete clinical response to neoadjuvant chemotherapy, modified radical mastectomy is recommended in the treatment of IBC, followed by post-mastectomy radiation therapy. (See "Inflammatory breast cancer: Clinical features and treatment", section on 'Locoregional treatment'.)

●Multicentric disease, defined as two or more primary tumors in separate quadrants of the breast such that they cannot be encompassed in a single excision, has classically been considered an absolute contraindication to BCT. However, this may be changing for select patients. In the Alliance Z11102 trial, 198 women with two (96 percent) or three (4 percent) separate sites of biopsy-proven malignancy separated by ≥2 cm within the same breast underwent BCS with negative margins followed by whole breast radiation with boost to all lumpectomy beds. Breast conservation was feasible in 93 percent, with 70 percent of patients having two separate lumpectomies. Surgery was completed in a single operation in 73 percent; only 7 percent required mastectomy due to positive margins [1]. At two years, the majority of women who underwent BCT reported good-to-excellent cosmesis [2]. At five years, the cumulative incidence of local recurrence was 3.1 percent (95% CI 1.3-6.4) [3]. For select patients with multicentric disease, where the tumors are small, have favorable histology, and two separate lumpectomies are technically feasible, BCT may be an option. However, because the Z11102 trial is a registry trial which could have allowed surgeons to selectively enroll patients with favorable results, further evidence is required for BCT to be routinely recommended for multicentric diseases.

Of note, the five-year local recurrence rate was much higher without preoperative magnetic resonance imaging (MRI) than with it (22.6 versus 1.7 percent) [3]. In that analysis, however, only 15 patients received preoperative MRI versus 189 patients who did not. This calls into question the generalizability of mandatory MRI to make sure there are no other areas of suspicion prior to proceeding with more than one lumpectomy, especially in light of the plethora of data demonstrating that MRI does not improve surgical outcomes (See "Diagnostic evaluation of suspected breast cancer", section on 'Impact of preoperative breast MRI'.)

●Diffuse malignant microcalcifications on mammography.

●A history of prior therapeutic radiation therapy (RT) that included a portion of the affected breast, which, when combined with the proposed treatment, would result in an excessively high total radiation dose to the chest wall. The two most common scenarios are prior mantle radiation to the chest wall for Hodgkin lymphoma and prior whole breast radiotherapy for breast cancer. Although there is ongoing research exploring the potential of 3D conformal partial breast reirradiation in selected patients who have an in-breast recurrence and prior whole breast irradiation [4], it is still investigational.

●The use of breast irradiation is contraindicated during pregnancy, but BCT is an option during pregnancy if the timing works out so that the radiation may be delivered postpartum. Thus, breast cancer diagnosed during the first trimester should be treated with mastectomy. Breast cancer diagnosed during the second or third trimester can be managed with BCS followed by adjuvant chemotherapy or with neoadjuvant chemotherapy followed by surgery, with the radiotherapy delivered postpartum. For breast cancer diagnosed late in the third trimester, it may be possible to perform BCS in the third trimester, deferring breast irradiation until after delivery. Breast cancer during pregnancy is further discussed elsewhere. (See "Gestational breast cancer: Epidemiology and diagnosis" and "Gestational breast cancer: Treatment".)

●Persistently positive resection margins despite multiple attempts at re-excision after BCS [5].

●Some patients with a history of connective tissue disease tolerate irradiation poorly, and so the use of radiation as a component of BCT must be weighed against the possible complications [6-8].

•Scleroderma and Sjögren disease are contraindications to radiation because of cutaneous fragility [6]. Breast cancer patients with these two connective tissue disorders should undergo mastectomy instead of BCT.

•Systemic lupus erythematosus and rheumatoid arthritis can also increase risk of radiation toxicity, but data are sparse. Thus, management of breast cancer in patients with these two conditions can be individualized [8,9].

Relative contraindications for BCT — Tumor size relative to breast size is an important consideration in selecting patients for BCS. A large tumor in a small breast is a relative contraindication, since an adequate resection would result in significant cosmetic alteration.

However, breast size in itself is not a contraindication to BCT. Women with large or pendulous breasts can undergo breast irradiation successfully as long as reproducibility of patient setup can be ensured and it is technically possible to obtain adequate dose homogeneity. It is now widely accepted that patient eligibility for BCS is determined more by the anticipated cosmetic result, as well as the ability to achieve margin control and deliver adjuvant radiation, than by the size of the primary tumor [10].

Tumor size in itself is not an absolute contraindication to BCT either. Neoadjuvant treatment with chemotherapy or hormonal therapy can reduce tumor size significantly and allow for breast conservation with acceptable rates of local recurrence [11]. Whether a patient is eligible for BCS is dependent on the extent of tumor involvement after, not before, neoadjuvant treatment. (See 'Neoadjuvant therapy prior to BCT' below and "General principles of neoadjuvant management of breast cancer".)

Not a contraindication for BCT — The pool of candidates for BCT is expanding commensurate with advances in neoadjuvant therapy, surgical and radiation therapy techniques, and pathologic evaluation [12]. Factors that are no longer considered contraindications for BCT include the following:

●Age is not a contraindication for BCT. For older women, physiologic age and the presence of comorbid conditions should be the primary determinants of local therapy, rather than chronological age. Young age, which is defined as ≤40 years in the majority of studies, by itself, is not a contraindication to BCT and is a prognostic rather than predictive factor [13-22]. Furthermore, the recurrence rates after BCT are very similar to those after mastectomy in young women in contemporary series [23,24]. However, bilateral mastectomy may be preferred among relatively younger patients with hereditary breast cancer, such as BRCA1/BRCA2 mutation carriers, or those with a strong family history. In those patients, bilateral mastectomy serves a risk-reducing purpose.

●Local involvement or retraction of the skin or nipple-areolar complex does not necessarily contraindicate BCT. However, a portion of skin or the nipple-areolar complex will likely need to be resected to achieve negative margins, so the cosmetic implications of this should be factored into the decision to proceed with BCT.

●Histologic subtypes other than invasive ductal carcinoma (eg, invasive lobular cancer) are not associated with an increased risk of breast cancer recurrence; these women are candidates for BCT if the tumor distribution is not diffuse and it can be excised with negative margins.

Because tumors with a lobular histology often present insidiously, it may be more difficult to perform BCS in these patients [25]. However, as long as negative margins can be obtained, the local control of invasive lobular cancer is comparable to that in invasive ductal cancer. The presence of lobular carcinoma in situ (LCIS) does not affect rates of local recurrence, and classic LCIS at lumpectomy margins has no clinical significance and does not warrant a re-excision. Pleomorphic LCIS, however, behaves more like ductal carcinoma in situ and does require margin clearance. (See "Atypia and lobular carcinoma in situ: High-risk lesions of the breast" and "Pathology of breast cancer".)

●Extensive intraductal component (EIC) is defined as an invasive ductal carcinoma in which intraductal cancer (ductal carcinoma in situ [DCIS]) is present in greater than 25 percent of the tumor. Both requirements must be met before EIC can be diagnosed. Because EIC refers to the DCIS component of an invasive cancer, it does not apply to pure DCIS.

The presence of EIC is an indicator that disease extent may be greater than clinically suspected. While EIC-positive cancers with a positive margin have a higher rate of local recurrence compared with EIC-negative cancers, EIC-positive cancers with negative resection margins do not have an increased risk of ipsilateral recurrence following BCT [26]. Thus, EIC is not a contraindication to BCT by itself, though routine assessment of the margins of resection is an important component of the histologic evaluation in women with an EIC; patients with negative margins are still acceptable candidates for BCT. (See "Breast ductal carcinoma in situ: Epidemiology, clinical manifestations, and diagnosis".)

●Lymph node positivity is a marker of worse prognosis, but positive lymph nodes are not a contraindication for BCT, as BCT and mastectomy have equivalent outcomes independent of nodal metastases.

●Tumor location should not dictate but can influence the choice of treatment. Tumors in a superficial subareolar location may require resection of the nipple-areolar complex to achieve negative margins; oncologic outcomes will not be affected, but the cosmetic result may be. Although oncoplastic techniques improve cosmesis, the patient and their clinician need to assess whether such a resection is preferable to mastectomy.

●An inherited susceptibility to breast and other cancers has been linked to germ-line mutations in BRCA1 and BRCA2 genes in some women. Young women with a strong family history of either breast or ovarian cancer have a significant probability of harboring one of the mutations and should be offered genetic counseling about these mutations. (See "Overview of hereditary breast and ovarian cancer syndromes" and "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes".)

Although a family history of breast cancer is not a contraindication to BCT, women with hereditary breast cancer (eg, BRCA1 or BRCA2 mutation carrier) should be informed about their increased risk of a second primary cancer, and that bilateral mastectomy may reduce that risk. However, those contemplating bilateral mastectomy must understand that contralateral prophylactic mastectomy (CPM) has not been shown to have a survival benefit [27]. That is because the survival rates tend to be driven by the metastatic potential of the first cancer and mastectomy does not eliminate the risk of either a chest wall recurrence or a new primary. (See "Cancer risks and management of BRCA1/2 carriers without cancer" and "Overview of hereditary breast and ovarian cancer syndromes".)

The decision whether to pursue BCT in known BRCA1 or BRCA2 mutation carriers should be made following extensive discussion with an experienced surgeon and a genetics counselor.

●BCS is not contraindicated for women with dense breast tissue. In a prospective study of 1052 patients undergoing attempted BCS, patients with dense breast tissue were significantly more likely to be treated with an initial mastectomy compared with women with less dense breast tissue (74 versus 52 percent, odds ratio [OR] 1.94, 95% CI 1.44-2.62) [28]. This may reflect surgeon or patient bias rather than an inability to fulfill criteria for BCS.

In addition, MRI was performed more often in patients with dense breast tissue (65 versus 33 percent). However, breast density was not associated with positive margins for BCS or conversion to a mastectomy, and preoperative MRI did not decrease the risk of positive margins. (See 'Preoperative evaluation' below.)

Mastectomy is mandatory for tumor control in patients with breast cancer and one or more absolute contraindications for BCT, and it may provide more satisfactory outcomes in others. The specific indications and techniques of mastectomy are discussed separately. (See "Mastectomy".)

Shared decision making — In the past, BCT was underutilized in the United States [29-32] due to both surgeon and patient reasons [33-36]. To inform an optimal choice, the individual patient's needs and expectations should be accurately assessed. This requires that the patient and clinician discuss the benefits and risks of mastectomy versus BCT in regards to long-term survival, the likelihood and consequence of local recurrence, and the impact on cosmetic outcome and psychosocial adjustment. (See 'Outcomes' below.)

To dispel a common misconception that mastectomy is a more "aggressive" approach to treating cancer that guarantees that they will never have to deal with cancer or additional treatment again, patients should be clearly told that [37]:

●BCT and mastectomy have equivalent survival outcomes. (See 'Survival' below.)

●Mastectomy does not eliminate the possibility of local recurrence or new primary cancer. (See "Clinical manifestations and evaluation of locoregional recurrences of breast cancer".)

●Adjuvant radiotherapy may still be indicated after mastectomy if there are clinical features of increased risk of chest wall recurrence.

●Decisions about chemotherapy are made independent of surgical approaches (ie, BCS versus mastectomy). (See "Overview of the treatment of newly diagnosed, invasive, non-metastatic breast cancer", section on 'Adjuvant systemic therapy'.)

Studies show that only 50 to 70 percent of women with early breast cancer actively participate in the surgical decision [35,38]. The use of decision aids (paper, visual, audiotape, or computerized audiovisual) can enhance patient knowledge of treatment options [39].

PREOPERATIVE EVALUATION — Patients diagnosed with breast cancer should undergo the following evaluation, the result of which helps determine if each individual is a better candidate for breast-conserving therapy (BCT) or mastectomy [9,40]:

●A complete history and physical examination.

●Tissue biopsy with core needle sampling to provide conclusive proof of malignancy. Needle biopsy is preferred over surgical biopsy to reduce unnecessary surgery and avoid scars that may complicate the placement of the subsequent lumpectomy incision. (See "Breast biopsy".)

●Accurate histologic assessment of the primary tumor, including histologic subtype, hormone receptor status, and HER2 status. (See "Pathology of breast cancer" and "Prognostic and predictive factors in early, non-metastatic breast cancer", section on 'Receptor status' and "HER2 and predicting response to therapy in breast cancer", section on 'Testing for HER2 expression' and "Hormone receptors in breast cancer: Clinical utility and guideline recommendations to improve test accuracy", section on 'Assays for ER and PR' and "Prognostic and predictive factors in metastatic breast cancer", section on 'Tests done on metastatic tissue'.)

●Once the diagnosis of cancer is made, multidisciplinary coordination among breast and reconstructive surgeons, radiation and medical oncologists, and radiologists and pathologists facilitates treatment planning and streamlines patient care [41]. If chemotherapy is indicated based on tumor stage and histology, delivery in the neoadjuvant setting may downstage the primary tumor and allow for BCS in patients who may otherwise require mastectomy. (See "Diagnostic evaluation of suspected breast cancer" and "General principles of neoadjuvant management of breast cancer" and 'Neoadjuvant therapy prior to BCT' below.)

●Preoperative breast imaging to define the extent of disease and identify multifocal or multicentric cancer that could preclude breast conservation or make it difficult to achieve clear surgical margins. Imaging typically includes a combination of bilateral mammographic evaluation with appropriate magnification views and ultrasound, if appropriate. The tumor size should be included in the mammographic report, as well as documentation of associated microcalcifications, and the extent of the calcifications within and outside the mass (if present). (See "Clinical features, diagnosis, and staging of newly diagnosed breast cancer", section on 'Assessing the extent of local disease'.)

●Although breast MRI is incorporated in the workup of some patients for BCT, its routine use in this setting is not standard. Studies have confirmed that breast MRI results in higher mastectomy rates but does not reduce re-excision or local recurrence rates in patients who undergo BCT [42].

Possible candidates for preoperative breast MRI include women with hereditary breast cancer and those with axillary metastasis but mammography-occult primary breast tumor [43]. The use of MRI for newly diagnosed breast cancer is discussed separately. (See "Diagnostic evaluation of suspected breast cancer", section on 'Indications for preoperative breast MRI'.)

Neoadjuvant therapy prior to BCT — The benefits of neoadjuvant chemotherapy in women with unresectable breast cancer were recognized several decades ago, although successfully downstaged patients routinely underwent mastectomy in that era. Subsequent studies confirmed that the neoadjuvant approach to chemotherapy can also increase the volume of patients who are eligible for breast-conserving surgery (BCS) without increasing local recurrence rate [12]. (See "General principles of neoadjuvant management of breast cancer".)

Before the initiation of neoadjuvant therapy, all cancer-related information must be available to the treatment team. In case of a complete response to chemotherapy, a metal clip must be placed in the tumor bed to guide BCS, or else a mastectomy is performed. Since it is not possible to predict response to neoadjuvant therapy, a metal clip should be placed in the tumor bed under ultrasound guidance in all patients considering BCT before or soon after neoadjuvant treatment begins.

The standard of care is for all patients to undergo definitive breast surgery, either BCS or mastectomy, after the completion of neoadjuvant therapy, even for those who are fortunate enough to achieve a complete response. Breast imaging should be repeated after completion of neoadjuvant chemotherapy to assess the patient's response and facilitate surgical planning. A patient's candidacy for BCT is determined by the extent of tumor involvement after, not before, neoadjuvant therapy. While neoadjuvant therapy downstages the cancer and increases the likelihood of BCT in most patients, occasionally it may unmask previously obscured microcalcifications that may still exclude a patient from BCT.

While hormone-receptor-positive and HER2-negative tumors are less likely to have pathologic complete response rates, the surgical conversion rate from mastectomy to BCS as a result of neoadjuvant therapy is still over 50 percent [44]. If chemotherapy is indicated, neoadjuvant treatment may still allow for BCS. Neoadjuvant endocrine therapy is an alternative option for this patient population, but clinical response tends to be slow and incomplete [45,46].

BREAST-CONSERVING SURGERY — Breast-conserving surgery (BCS) involves excision of the primary tumor (ie, lumpectomy) and evaluation of the axillary lymph nodes (most commonly with sentinel lymph node biopsy [SLNB]) for invasive tumors.

Lumpectomy

Incision — The type and location of the incision is important for several reasons. Because any patient who undergoes lumpectomy may ultimately require a mastectomy, lumpectomy incisions should be planned with possible mastectomy incisions in mind (figure 1). In general, the incision should be placed close to the tumor to avoid extensive tunneling.

●In the upper part of the breast, incisions should be curvilinear or transverse and follow the natural skin creases (Langer's lines).

●In the lower part of the breast, the choice of a curvilinear or radial incision is dependent upon the contour of the breast, the distance from the skin to the tumor, and the amount of breast tissue to be resected.

●In many patients, incisions may be placed along the lateral contour of the breast, within the inframammary fold, or circumareolar, to improve the cosmetic outcome and hide the scar, even though these recommendations may deviate from the above principles. Factors such as the size of the tumor and likelihood of subsequent mastectomy and the extent of tunneling necessary should be considered when planning the incision.

Incisions for planned oncoplastic techniques are discussed separately. (See "Oncoplastic breast surgery".)

Prior to making the incision, there may be a benefit to injecting lidocaine around the tumor beyond pain management. In a multicenter, randomized trial involving over 1000 patients, peritumoral injection of 0.5% lidocaine prior to incision resulted in improved five-year disease free survival (86.6 versus 82.6 percent, p = 0.017) and five-year overall survival (90.1 versus 86.4 percent, p = 0.019) [47]. The mechanism is unknown but is thought to reduce the surgical stress response that may induce metastases [48]. The study protocol deviates from what may be considered standard treatment in many clinical practices, so further validation is necessary. However, given the simplicity and minimal costs associated with this intervention, it may be a reasonable approach.

Tissue handling — For deeper lesions, it is not necessary to remove skin, and preservation of the subcutaneous fat and avoidance of thin skin flaps are important in maintaining a normal post-treatment breast contour. If the tumor is superficial, it may be necessary to remove the overlying skin. Skin removal with a curvilinear incision in the inferior breast distorts the breast contour and should be avoided. Therefore, a radial incision is preferred for removing inferior lesions where skin excision is required. It is also not necessary to remove needle tracks from core needle biopsies or fine needle aspirations.

Closure — At the completion of the procedure, the incision should be closed with a subcuticular suture to avoid cross-hatching of the skin.

Meticulous hemostasis during BCS is important because a large hematoma distorts the appearance of the breast and makes follow-up evaluation and the planning of adjuvant radiation more difficult. Reapproximation of the breast tissue without tissue advancement is best avoided since it can result in distortion of the breast contour, which may not be apparent with the patient supine on the operating table [9].

Cosmetic outcomes can be improved with oncoplastic techniques of closure when:

●The lumpectomy is large in relation to the size of the breast (eg, >20 percent in breast volume or 80 grams in breast tissue weight)

●The cancer location requires repositioning of the nipple-areolar complex (NAC)

The specific techniques vary with the location of the cancer in the breast and are discussed in detail elsewhere. (See "Oncoplastic breast surgery".)

Margins of resection — Microscopic resection margins are the major selection factor for BCT because of their marked influence on local recurrence: women with negative excision margins have low rates of local recurrence following BCT [26,49], while positive resection margins (ie, carcinoma at the inked margin) are associated with a higher risk of local recurrence [26,49-51].

What constitutes an adequate excision margin for BCT has been hotly debated; the current consensus differs depending on whether the cancer is invasive or in situ:

Margins for invasive cancer — A multidisciplinary panel convened by the Society of Surgical Oncology and the American Society for Radiation Oncology recommended using "no ink on tumor" as the standard margin for patients with stages I and II invasive breast cancer treated with BCS followed by whole breast irradiation [52].

The recommendation was based on a meta-analysis of 33 studies, including 28,162 patients and 1506 ipsilateral breast tumor recurrences (IBTRs) [53]. At a median follow-up of 79.2 months, the median prevalence of IBTR was 5.3 percent (interquartile range 2.3 to 7.6 percent). A positive margin, defined as ink on tumor, was associated with a greater than twofold increase in IBTR (odds ratio [OR] 2.44, 95% CI 1.97-3.03). Margins wider than "no ink on tumor," however, were not associated with any lower incidence of IBTR. In 2020, this meta-analysis was updated to include 38 studies and 54,502 patients [54]. After a median follow-up of 7.25 years, the absolute local recurrence rates decreased over time for each margin width cohort, while the relative local recurrence rates between different margin groups remained stable over time. This continues to support the consensus guideline of "no tumor on ink’" for the majority of patients.

These guidelines apply only to patients treated with whole breast radiation and cannot be applied to patients receiving neoadjuvant therapy, partial breast irradiation, or those not receiving radiotherapy at all. Patients who have invasive breast cancer with a ductal carcinoma in situ (DCIS) component should be treated according to the invasive cancer guidelines on optimal margin width. (See 'Margins for DCIS' below.)

These guidelines were endorsed by the American Society of Clinical Oncology with two caveats [55]:

●Prior to radiation, postexcision mammography is necessary in patients with microcalcifications to ensure adequate resection of the primary disease.

●Flexibility in application was advocated because the guidelines were mostly based on retrospective studies that have significant selection bias, the intrinsic limitations of which remain despite the use of meta-analysis [56]. In addition, although the meta-analysis found an increased risk of IBTR following excision with close margins (as defined by each individual study), as opposed to negative margins (OR 1.74, 95% CI 1.42-2.15), this risk was not emphasized in the guidelines due to the heterogenous definitions of a close margin between studies [53].

Given these concerns and limitations, while routine re-excision is not necessary for a close margin (eg, <2 mm), an individual patient's clinical and pathologic features should guide the decision to perform re-excision in selected patients [57,58]. Factors to consider may include patient age, the size of the close margin (focal versus broad), discrepancies between radiographic and pathologic tumor sizes, and the morbidity involved with a re-excision lumpectomy. The decision whether or not to re-excise should be made in a multidisciplinary fashion, with input from the radiologists, pathologists, surgeons, and radiation oncologists [58].

Margins for DCIS — A multidisciplinary panel convened by the Society of Surgical Oncology, American Society for Radiation Oncology, and American Society of Clinical Oncology recommended a 2 mm margin as the standard for patients with DCIS treated with BCS followed by whole breast irradiation [59].

The recommendation was based on a meta-analysis of 20 studies, including 7883 patients with DCIS and known margin status [60]. All patients underwent BCS followed by whole breast irradiation; approximately 20 percent received endocrine therapy. After a median follow-up of 78.3 months, 865 patients developed recurrences; the median prevalence of IBTR was 8.3 percent (interquartile range 5 to 12 percent). Patients with positive margins defined as a margin <2 mm had a twofold higher risk of developing IBTR compared with those with negative margins (24 versus 12 percent), and approximately one-half of the recurrences were invasive disease. The reduction in IBTR was similar in patients with a margin of 2 mm (OR 0.51, 95% CI 0.31-0.85), 3 or 5 mm (OR 0.42, 95% CI 0.18-0.97), and 10 mm (OR 0.60, 95% CI 0.33-1.08).

The consensus panel advised clinical judgment when determining whether patients with smaller negative margin width (>0 or 1 mm) require re-excision. In some studies, patients with clear but narrower than 2 mm margins did not have worse outcomes [61,62]. Patients who have DCIS with extension of cancer cells beyond the basement membrane but no focus more than 0.1 cm in the greatest dimension (ie, DCIS-M) should be treated the same way as DCIS patients when determining optimal margin width.

Some surgeons advocate differential treatment for patients who plan or do not plan to undergo adjuvant radiation therapy (RT). In a retrospective analysis of over 1400 patients who underwent surgery for DCIS between 1996 and 2010, a negative margin width <2 mm was associated with locoregional recurrence (LRR) [63]. However, the association differed by adjuvant RT status. For patients who did not undergo RT, those with a margin <2 mm were more likely to develop an LRR than those whose margins are wider (10 year LRR rate 31 versus 5 percent), whereas the 10 year LRR rates were similar in patients who received adjuvant RT regardless of the margin width (4.8 percent with a <2 mm margin versus 3.3 percent with a ≥2 mm margin).

Techniques to reduce positive margins in BCS — Because positive margins are associated with a twofold increase in local recurrence rate [53], reoperation is frequently necessary after initial BCS to obtain negative margins. In the United States, BCS has an aggregate reoperation rate of 21.6 percent even with contemporary imaging methods [64], at a per annum cost of 228 million dollars [65]. Tools that can be used to reduce reoperation rates and improve cosmetic outcomes of BCS include specimen orientation and radiography, intraoperative margin assessment, and post-excision cavity shaving [66], which are discussed in a separate, dedicated topic. (See "Techniques to reduce positive margins in breast-conserving surgery".)

Evaluation of the axilla — Evaluation of the axilla provides information for treatment decisions in patients undergoing BCT for invasive breast cancer but generally not for DCIS. (See "Overview of management of the regional lymph nodes in breast cancer".)

For patients undergoing BCS who have a clinically negative axillary examination, SLNB is generally the standard initial approach. Axillary lymph node dissection (ALND) is reserved for those with clinically positive axillary nodes or who have three or more positive nodes with SLNB (completion ALND). (See "Overview of sentinel lymph node biopsy in breast cancer".)

The management of microscopically positive axillary nodes (with needle biopsy) and axillary nodes after neoadjuvant chemotherapy is more nuanced, which is discussed elsewhere. (See "Overview of sentinel lymph node biopsy in breast cancer", section on 'Preoperative axilla evaluation' and "General principles of neoadjuvant management of breast cancer", section on 'Management of the axilla'.)

ADJUVANT RADIATION THERAPY — Most women require whole breast radiation to eradicate any tumor deposits remaining following breast-conserving surgery (BCS). Doing so reduces risk of locoregional recurrence and improves breast cancer-specific and overall survival. Patients who may not require radiation, such as older women with estrogen receptor (ER)-positive tumors, and radiation regimens are discussed in another topic. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

COMPLICATIONS — Complications after breast-conserving surgery (BCS) include seroma formation, hematoma formation, wound infection, and arm morbidity. Some of the complications are directly attributable to surgery, while others are caused by a culmination of both surgery and adjuvant radiation. A validated risk calculator can estimate a breast cancer patient's unique risk of acute complications following each surgical intervention, including BCS [67].

Seroma — It is accepted that serous fluid will accumulate in the surgical bed in virtually all patients after breast and axillary surgery; most are clinically silent [68]. A clinically significant seroma is defined as a postoperative fluid collection that requires one or more aspirations or subsequent drain placement [69]. In a retrospective review of 324 patients who underwent 561 breast or axillary surgeries, 8.4 percent developed a seroma that required intervention [69]. Seroma rates were significantly lower after breast-conserving surgery than after mastectomy (6 versus 14 to 16 percent).

The presence of a seroma significantly increases the risk of a concurrent or subsequent surgical site infection (8.5 versus 4 percent in the absence of a seroma). Prolonged seroma formation may also delay wound healing.

Hematoma — Hematoma formation is a known complication of BCS. Most postoperative hematomas can be managed with either observation or an in-office drainage or aspiration procedure, and only a minority of hematomas require operative evacuation. In a retrospective study of 2724 patients undergoing lumpectomy and sentinel lymph node biopsy, the 30 day risk of any hematoma was about 4 percent, and 0.5 percent required operative evacuation [70].

Wound infection — Wound infections from BCS are rare. In a retrospective analysis of acute complications from National Surgical Quality Improvement Program (NSQIP) data from 2005 to 2017, the overall wound infection rate after partial mastectomy and oncoplastic resection were 1.4 and 1.76 percent, respectively, and those rates have changed very little over time [71].

BCS may also be associated with the relatively late occurrence of a postoperative breast abscess (median 5 months, range 1.5 to 8.0 months) [72]. Necrosis of marginally viable fat in the lumpectomy cavity may contribute to this problem.

Older adults — The risk of postoperative complications increases with increasing age as well as associated comorbid illnesses after both mastectomy and BCT. In a retrospective review of 3672 patients age 65 years and older with invasive or noninvasive breast cancer, patients >85 years old were more likely to develop complications compared with the overall complication rate (25.1 versus 19.4 percent, odds ratio [OR] 1.85, 95% CI 1.37-2.50) [73]. In addition, women aged 65 to 69 years had a significantly lower complication rate of 15.3 percent. The most common complications included wound infection and bleeding for all ages 65 and older, including women >85 years. Mastectomy was associated with more complications than BCT (OR 1.72, 95% CI 1.42-2.09) in the older patient population.

Long-term — Long-term complications of BCT include radiation fibrosis, lymphedema, and chronic pain, which are presented elsewhere. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse", section on 'Long-term adverse effects of primary therapy' and "Overview of breast reconstruction".)

OUTCOMES

Survival — Between 1961 and 1989, multiple international randomized clinical trials were performed to directly compare breast-conserving therapy (BCT) with mastectomy [74-82]. These trials consistently demonstrated similar overall and breast disease-specific survival (DSS) between the two approaches [83-85]. Since then, BCT has been considered at least equivalent to mastectomy in survival outcomes.

Since 2013, a growing number of studies, both in the United States and internationally, have associated BCT with better survival than mastectomy [86], regardless of age [87,88], stage [89,90], tumor characteristics, and cancer phenotypes [91,92]. As examples:

●One cohort study of over 110,000 Californian women with stage I or II breast cancer associated BCT with better overall survival (OS) than mastectomy without radiation (adjusted hazard ratio [HR] 0.81, 95% CI 0.80-0.83) [93]. The DSS benefit was more pronounced among women age ≥50 with hormone-receptor-positive disease (HR 0.86, 95% CI 0.82-0.91) but was seen in all subgroups analyzed regardless of age, hormone receptor status, and cancer phenotypes.

●In a population-based study from the Netherlands that included over 170,000 patients, BCT conferred a survival advantage over mastectomy (HR 0.87, 95% CI 0.81-0.93) following correction for stage, age, and adjuvant therapies [94].

●In a population-based study of 214,128 women who underwent BCT or mastectomy for stage I or II breast cancer from the Surveillance, Epidemiology, and End Result cancer registries, BCT yielded better survival than mastectomy in all subtypes (luminal A, luminal B, triple negative, and HER2 enriched) [92].

●In a meta-analysis of 14 studies including 19,819 patients with triple-negative breast cancer, the all-cause mortality among women undergoing BCT was lower than that among those undergoing mastectomy (pooled hazard ratio 0.78, 95% CI 0.69-0.89) [95]. The locoregional recurrence rate and distant metastasis rate were lower following BCT as well.

●In a meta-analysis of 30 studies (6 randomized trials and 24 retrospective reviews) including over 1,800,000 patients with follow-up ranging from 4 to 20 years, BCT is associated with improved OS compared with mastectomy (relative risk [RR] 0.64, 95% CI 0.55–0.74) [96]. Furthermore, the benefit of BCT was stronger in patients who had less than 10 years of follow-up (RR 0.54, 95% CI 0.46–0.64).

However, all of these were observational studies, which could be confounded by selection bias. Thus, BCT is still considered "at least" equivalent, rather than superior to, mastectomy in survival outcomes. Both approaches are acceptable options that should be selected based upon multidisciplinary clinician input and patient preference. (See 'Patient selection for BCT' above.)

The biologic plausibility of a more limited procedure (BCS) being superior to a more radical surgery (mastectomy) can potentially be explained by the impact of adjuvant radiotherapy (RT) [97] and the fact that mastectomy may not remove all breast tissue (thus leaving behind microscopic cancer foci) [98].

Indeed, we know that the success of BCT is contingent upon moderate-dose RT in eliminating subclinical foci of disease in the ipsilateral breast. Adjuvant RT has been shown to substantially reduce the risk of in-breast recurrences [75]. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

Additionally, the isolated axillary recurrence rate after BCT has been shown to be lower than that after mastectomy without radiation (1.1 versus 3.5 percent) in a prospective nonrandomized study with 13 year follow-up [99]. In that study, both overall survival (79.5 versus 64.3 percent) and disease-free survival (90.5 versus 84 percent) were better after BCT than after mastectomy, although the ipsilateral breast or chest wall recurrence-free survival rates were not statistically different (90.5 percent BCT versus 95 percent mastectomy; p = 0.428). Thus, the survival benefit of BCT should at least be partially attributed to the protective effect of radiation. The tangential radiation fields originating from whole breast irradiation may help reduce recurrence by controlling minimal residual disease in the lower axilla.

Local recurrence — Local control is important to overall survival because local failure is a risk factor for distant metastasis [100]. Rough estimates indicate that one patient may die from breast cancer for every four local recurrences [98].

A higher locoregional recurrence rate for BCT was reported in some of the early trials comparing BCT with mastectomy [101]. In randomized studies using variable surgical and radiation techniques, long-term recurrence rates in the treated breast following BCT ranged from 5 to 22 percent, compared with 4 to 14 percent with mastectomy [75-79,81,82]. In those days, the risk of local recurrence after BCT was estimated to be around 1 percent per year, or 10 percent at 10 years. However, the higher local recurrence rate did not appear to negatively impact survival [102].

Since then, better imaging, more attention to margins, and more effective and longer durations of systemic therapy have reduced local recurrence rate after BCT to just 2 percent at 10 years [103]. Thus, the local recurrence rate after contemporary treatment with BCT is no longer considered higher than that after mastectomy [104].

The local recurrence rate following BCT increases with young age, positive surgical margins, node positivity, estrogen receptor negativity, and absence of radiation therapy [22]. It is important to realize that these factors are not contraindications to BCT, but their presence may influence the choice of treatment. (See 'Not a contraindication for BCT' above.)

Cosmetic outcome — In addition to local recurrence, another major goal of BCT is the preservation of a cosmetically acceptable breast. With modern treatment techniques, an acceptable cosmetic outcome can be achieved in almost all patients without compromising local tumor control.

Many surgical factors will play a role in the ultimate cosmetic appearance of the breast. These include the size and placement of the incision, management of the lumpectomy cavity, and the extent of axillary dissection if necessary. The surgeon has control over several of these issues, and careful attention to detail will improve the aesthetic results [105]. (See 'Breast-conserving surgery' above.)

The amount of resected breast tissue is the major determinant of appearance following BCS. Oncoplastic surgical techniques allow resection of a breast cancer with wide surgical margins while preserving the shape and appearance of the breast. Patients with either a large tumor relative to their breast size or a central tumor are candidates for oncoplastic resections. Long-term outcomes of oncoplastic surgery are comparable or superior to those of standard breast conservation surgery. (See "Oncoplastic breast surgery".)

Adjuvant radiotherapy can also influence cosmetic outcomes by causing skin fibrosis. The primary approach to prevention of radiation-induced fibrosis is through the use of appropriate radiation therapy doses and techniques that minimize the radiation exposure for normal tissue. For patients with established radiation-induced fibrosis, treatment is primarily symptomatic and includes a combination of pentoxifylline and tocopherol (vitamin E). (See "Clinical manifestations, prevention, and treatment of radiation-induced fibrosis".)

Although treatment-related changes in the breast stabilize at approximately three years, other factors that affect the untreated breast, such as change in size because of weight gain or the normal ptosis seen with aging, continue to affect breast symmetry. Such less-than-ideal cosmetic results can be remedied by reconstruction of the ipsilateral or contralateral breast. (See "Overview of breast reconstruction".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Breast surgery" and "Society guideline links: Breast cancer".)

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 5^th to 6^th 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 10^th to 12^th 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: Choosing surgical treatment for early-stage breast cancer (The Basics)")

●Beyond the Basics topics (see "Patient education: Breast cancer guide to diagnosis and treatment (Beyond the Basics)" and "Patient education: Surgical procedures for breast cancer — Mastectomy and breast-conserving therapy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Breast-conserving therapy (BCT) allows women with early invasive breast cancer to preserve their breast without sacrificing oncologic outcome. Successful BCT requires complete surgical removal of the tumor (with negative surgical margins) followed by radiation therapy to eradicate any residual disease. (See 'Introduction' above.)

●Patient selection for BCT – Patient selection is crucial to the success of BCT. BCT should be offered unless:

•It is not possible to obtain margin control with breast-conserving surgery (BCS) (eg, inflammatory breast cancer, multicentric disease, diffuse malignant microcalcifications, or persistent positive margins despite multiple re-excisions).

•There is a contraindication to adjuvant radiation therapy (eg, pregnancy, prior breast irradiation, scleroderma, or Sjögren disease).

Cosmetic concerns do not dictate but can influence procedure choice (eg, large tumor in a small breast, breast asymmetry, or postradiation fibrosis). (See 'Patient selection for BCT' above.)

●Neoadjuvant chemotherapy – Neoadjuvant chemotherapy has been shown to increase eligibility for BCT. Before the initiation of neoadjuvant therapy, a clip should be placed in the tumor bed to guide BCS. After completion of neoadjuvant chemotherapy, breast imaging should be repeated to determine a patient's candidacy for BCT. All patients should undergo definitive breast surgery, either BCS or mastectomy, including those who are fortunate enough to achieve a complete response. (See 'Neoadjuvant therapy prior to BCT' above and "Neoadjuvant management of newly diagnosed hormone-positive breast cancer".)

●Breast surgery – BCS involves excision of the primary tumor (ie, lumpectomy) to negative margins (see 'Breast-conserving surgery' above):

•Margin for invasive breast cancer – For patients with stage I or II invasive breast cancer treated with BCS followed by whole breast irradiation, we recommend "no ink on tumor" as the standard margin (Grade 1B). However, we use an individualized approach to patients who have a close margin (eg, <1 mm) with regard to re-excision. (See 'Margins for invasive cancer' above.)

•Margin for DCIS – For patients with ductal carcinoma in situ (DCIS) treated with BCS followed by whole breast irradiation, negative margins are also required. We suggest a ≥2 mm rather than a narrower negative margin (Grade 2C) because a ≥2 mm margin may confer additional benefit for local recurrence over a narrower margin. However, we use an individualized approach to patients who have a close but negative margin (eg, >0 or 1 mm) with regard to re-excision. (See 'Margins for DCIS' above.)

Surgical evaluation of the axillary lymph nodes (most commonly with sentinel lymph node biopsy [SLNB]) is discussed elsewhere. (See "Overview of management of the regional lymph nodes in breast cancer", section on 'Axillary management'.)

●Adjuvant radiotherapy – Most women require whole breast irradiation to eradicate any tumor deposits remaining following breast BCS. Doing so reduces risk of locoregional recurrence and improves breast-cancer-specific and overall survival. There are exceptions (eg, older women with estrogen-receptor-positive tumor), which are discussed in another topic. (See "Adjuvant radiation therapy for women with newly diagnosed, non-metastatic breast cancer".)

●Comparison with mastectomy – Earlier randomized trials established that BCT and mastectomy have equivalent survival outcomes. Later observational studies suggested that BCT may have a slight survival advantage over mastectomy, but those studies are observational and may have inherent selection bias. Thus, it is now widely accepted that BCT is "at least" equal to mastectomy in terms of survival outcomes. (See 'Survival' above.)

While earlier trials reported a higher local recurrence rate after BCT than after mastectomy, it did not translate into worse survival. Since then, refinement in BCT techniques has reduced local recurrence rate to just 2 percent at 10 years, comparable to that of mastectomy. (See 'Local recurrence' above.)

●Cosmesis – Another major goal of BCT is the preservation of a cosmetically acceptable breast. Surgery and radiation can both influence cosmetic outcomes. Attention to surgical techniques, oncoplastic techniques, and breast reconstruction can all contribute to optimal cosmesis after BCT. (See 'Cosmetic outcome' above and "Oncoplastic breast surgery" and "Overview of breast reconstruction".)

ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge Lori J Pierce, MD, who contributed to earlier versions of this topic review.