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Contralateral prophylactic mastectomy

Contralateral prophylactic mastectomy
Literature review current through: Jan 2024.
This topic last updated: Aug 24, 2023.

INTRODUCTION — Patients with a unilateral sporadic breast cancer are at a modest risk of developing an invasive contralateral breast cancer (CBC). While most women never will develop a contralateral second primary breast cancer, risk-reducing strategies may be appropriate for some. A contralateral prophylactic mastectomy (CPM) is a risk-reducing mastectomy performed in the clinical setting for the patient diagnosed with an invasive or a noninvasive breast cancer. While there is no clear survival benefit for most breast cancer patients who do not carry a deleterious breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) mutation [1-3], the rates of performing a CPM have increased over the last several years [4,5].

The risk of a contralateral breast cancer, the decision-making process to undergo a CPM, and outcomes will be reviewed in this topic. Management of patients with invasive and noninvasive breast cancer, with and without an inherited genetic mutation, is reviewed separately. Medical therapy for breast cancer risk reduction is also reviewed separately.

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

(See "Ductal carcinoma in situ: Treatment and prognosis".)

(See "Overview of hereditary breast and ovarian cancer syndromes".)

(See "Cancer risks and management of BRCA1/2 carriers without cancer".)

(See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

RATIONALE — The rationale for CPM in a patient who has had breast cancer is to reduce the risk of contralateral breast cancer.

Risk of contralateral breast cancer among breast cancer patients is as follows:

For patients who present with unilateral breast cancer, the risk of developing a contralateral breast cancer is estimated to be 0.4 to 1.0 percent per year cumulative over their lifetime [6-10]. (See "Overview of long-term complications of therapy in breast cancer survivors and patterns of relapse".)

For patients with breast cancer who carry a deleterious breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) mutation, the risk of a contralateral breast cancer is approximately 10 to 25 percent [11,12]. However, some studies have estimated the risk to be as high as 65 percent for BRCA1 carriers and 50 percent for BRCA2 carriers [13]. (See "Genetic testing and management of individuals at risk of hereditary breast and ovarian cancer syndromes", section on 'Breast cancer risk management'.)

Other reasons for undergoing a CPM include relative ease of follow-up without a mammogram or magnetic resonance imaging (MRI), reduction of anxiety for occurrence of a second breast cancer, and desire for symmetry that can be achieved with bilateral mastectomies and reconstruction.

CANDIDATE SELECTION — Risk-reduction prophylactic mastectomy is often offered to patients with or without a previous history of breast cancer who carry a germline genetic mutation conferring a high risk for breast cancer (breast cancer susceptibility genes 1 and 2 [BRCA1/2], tumor protein p53 [TP53], phosphatase and tensin homolog [PTEN], cadherin 1 [CDH1], or serine/threonine protein kinase 11 [STK11] mutation), those with a strong family history of breast or ovarian cancer, and those with a history of thoracic radiation therapy at <30 years of age [14]. This approach is consistent with guidelines from the National Comprehensive Cancer Network. For those specifically who have had breast cancer, the decision for CPM takes into account many of the same factors that go into decisions about prophylactic mastectomy. However, the decision to undergo a CPM is frequently an individual patient’s choice and based on the management (eg, mastectomy) of the presenting breast cancer, the risk of contralateral disease given an ipsilateral cancer, their desire for symmetry, and anxieties regarding follow-up imaging. Family history, genetics, and other markers of increased risk may weigh on a patient’s decision regarding CPM.

Some subsets of patients may also be at high risk of epithelial ovarian and fallopian tube cancer and would benefit from risk-reducing bilateral salpingo-oophorectomy. This is discussed in detail elsewhere. (See "Risk-reducing salpingo-oophorectomy in patients at high risk of epithelial ovarian and fallopian tube cancer", section on 'Candidates'.)

While, previously, women with lobular carcinoma in situ were thought to be at significant risk such that bilateral prophylactic mastectomy was offered, a more preferable approach for such patients is risk-reducing medical therapy. (See "Atypia and lobular carcinoma in situ: High-risk lesions of the breast".)

DECISION-MAKING PROCESS — The decision to undergo a CPM is generally based upon the patient's personal preference as well as the surgical management of the presenting breast cancer (ie, mastectomy). Patients often state that their decision may be (in part) influenced by other people, including the surgeon, primary care clinician, friends, and/or family members. Hence, the patient and her surgeon should fully discuss the actual risks of a contralateral breast cancer in terms of the patient’s own personal and family history and her goals for treatment. (See 'Pretreatment counseling' below.)

Pretreatment counseling — The frequency of CPM has increased from nearly 4 percent in 2002 to almost 13 percent in 2012, despite a lack of survival benefit associated with the procedure [15]. It must also be recognized, however, that data involving CPM is not based on randomized trials, thus limiting our knowledge about potential improvements in survival. Providers should engage in a discussion with patients considering CPM regarding limitations in the data, the patient’s perceived versus the actual benefits of the procedure, and the accompanying risks. The likelihood of contralateral breast cancer should also be discussed. (See 'Rationale' above.)

Regarding potential benefits, evidence shows that the risk of contralateral breast cancer is reduced by CPM, and this may be sufficient rationale for some women at risk of a second breast cancer to pursue the procedure. However, it has been shown that the average woman overestimates her risk of contralateral breast cancer at the time of her initial breast cancer diagnosis [16]. Providers must therefore ensure patients have accurate data regarding their baseline level of risk as they make the decision regarding CPM. Furthermore, although many women opt for CPM in order to improve and extend life, available data, although limited, have shown a survival benefit only for those who carry deleterious breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) mutations [2,17]. Most women undergoing CPM, however, do not have such mutations or a strong family history [18]. Patients must also be made aware of the risks and complications of undergoing a CPM, as this involves a more extensive operation (bilateral mastectomies with or without bilateral reconstruction). (See 'Outcomes' below.)

Despite knowing that CPM does not clearly improve survival, women who have the procedure do so, in part, to extend their lives. Based upon a survey of 123 women with unilateral breast cancer, most women who undergo a CPM do so with a desire to reduce the risk of a contralateral breast cancer (98 percent) and improve survival (94 percent) [19]. However, only 18 percent believed that women undergoing a CPM lived longer. These discordant findings suggest that cognitive dissonance exists in decision-making. Although women understand that a CPM is unlikely to extend their survival, anxiety and fear of recurrence may be driving their decisions. Interventions aimed at improving risk communication in an effort to promote evidence-based decision making are warranted.

Factors influencing patient choice — A number of sociodemographic and tumor characteristics have been associated with a higher likelihood of pursuing CPM, including:

Younger age [4,6,20-23]

Being from a White population [4,21,22]

Private health insurance [21]

Family history of breast cancer [4,20,22-24]

Noninvasive histology [4]

Lobular tumor histology [22,23,25]

Other factors, such as preoperative evaluation with a bilateral breast magnetic resonance imaging (MRI) [4,24], failed attempt at breast conservation management [4], and the option of immediate reconstruction [4,22,24], are independently associated with the decision to pursue CPM.

OUTCOMES

Breast cancer risk reduction — The risks of a contralateral breast cancer in a woman with a personal history of breast cancer are about 4 percent over 10 years [26]. Family history affects this incidence. These data are discussed elsewhere. (See "Factors that modify breast cancer risk in women", section on 'Personal and family history of breast cancer' and "Factors that modify breast cancer risk in women", section on 'Medical and surgical risk reduction strategies'.)

In a Cochrane meta-analysis including 26 observational studies of contralateral risk-reducing mastectomy, risk of contralateral breast cancer was reduced consistently across the studies, but studies were inconsistent in regards to whether disease-specific survival was improved [27].

Benefits for CPM are likely higher for younger women. Based upon a prospective study of 745 women with breast cancer and a family history of breast and/or ovarian cancer undergoing a CPM, the risk reduction of a contralateral breast cancer (CBC) was approximately 96 percent [6]. In this cohort, the risk reduction following a CPM for women less than age 50 years was 94.4 percent (n = 388; number needed to treat [NNT] 3.6), and 96.0 percent for women 50 years of age and older (n = 357; NNT 7.4).

The likelihood of finding an occult invasive or noninvasive breast cancer in the CPM specimen, not identified on radiographic imaging (ie, mammogram, magnetic resonance imaging [MRI]), is low and reported to be approximately 1 to 2 percent [28,29].

Overall survival — Retrospective and observational data have not suggested an overall survival benefit for most breast cancer patients who undergo a CPM [15,30,31], though prospective randomized data are lacking. However, for patients with a deleterious breast cancer susceptibility gene 1 or 2 (BRCA1 or BRCA2) mutation, and in some studies, women diagnosed at a young age (<50 years), a survival benefit has been attributed to a CPM [1,2,5,17,32]. (See 'BRCA carriers' below.)

In a study of almost 500,000 women with unilateral stage I to III breast cancer enrolled in the Surveillance, Epidemiology, and End Results database, there was no improvement with CPM in either breast cancer-specific survival (hazard ratio [HR] 1.08, 95% CI 1.01-1.16) or overall survival (HR 1.08, 95% CI 1.03-1.14) compared with breast-conserving therapy alone [15]. Similarly, in a propensity matched analysis of almost 190,000 patients with stage 0 to III breast cancer in the California Cancer Registry, there was no significant mortality difference between those undergoing breast-conserving therapy or bilateral mastectomy (though both were associated with lower mortality than unilateral mastectomy) [30].

Results among younger women, however, are mixed [1,31,33]. For example, in a study of almost 15,000 women aged ≤45 years with stage I or II breast cancer, those receiving CPM and unilateral mastectomy versus unilateral mastectomy alone experienced no survival benefit [31]. By contrast, in an earlier risk-stratified analysis of almost 9000 women with early breast cancer enrolled in the Surveillance, Epidemiology, and End Results (SEER) database, CPM was associated with improved disease-specific survival (0.63, 95% CI 0.57-0.69), an effect that was due to improvements in breast cancer-specific mortality among patients ages 18 to 49 years with stage I to II estrogen receptor (ER)-negative breast cancer [1]. Five-year adjusted breast cancer survival for such patients was improved with CPM versus without (89 versus 84 percent).

For women with breast cancer who carry a deleterious BRCA1/2 mutation, a CPM can improve breast cancer survival [3,34]. (See 'BRCA carriers' below.)

Risks

Postoperative morbidity and mortality — Mortality rates are uniformly low (<1 percent) in patients undergoing an elective mastectomy [35,36]. However, morbidity associated with CPM occurs in one in eight women [37]. The complications of a mastectomy include seroma, surgical site infection (SSI), skin flap necrosis, nipple necrosis, postoperative pain, postmastectomy pain syndrome, phantom breast syndrome, arm mobility limitations, pneumothorax, brachial plexopathy, and the risks of an anesthetic and reconstruction, if performed. These complications are discussed separately elsewhere:

(See "Mastectomy", section on 'Complications'.)

(See "Clinical manifestations and diagnosis of postmastectomy pain syndrome".)

(See "Postmastectomy pain syndrome: Risk reduction and management".)

(See "Overview of post-anesthetic care for adult patients".)

(See "Overview of breast reconstruction".)

The frequency of complications following a bilateral mastectomy is greater than a unilateral mastectomy. For example, in one study of 352 women who underwent bilateral or unilateral mastectomy for breast cancer, more women undergoing bilateral mastectomy experienced complications (31 versus 23 percent), of which hematoma, skin necrosis, cellulitis, or seroma accounted for 84 percent of cases [37]. Of those undergoing bilateral mastectomy, morbidity occurred only in the prophylactic breast in 13 percent of cases, with half of these requiring reoperation. By contrast, in a separate study in 471 patients, contralateral prophylactic mastectomy was not associated with a greater 90-day reoperation rate for complications (although it was associated with increased hospital stays) [38].

Similarly, another retrospective review of the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) database of 4219 breast cancer patients between 2007 and 2010 found a higher rate of SSI in patients undergoing a CPM compared with a unilateral mastectomy (5.8 versus 2.9 percent) [39]. The 30-day complication rate following a CPM was significantly higher (7.6 versus 4.2 percent), even when adjusted for body mass index and smoking history (odds ratio [OR] 1.9, 95% CI 1.3-2.8).

Psychosocial effects

Body image, femininity — Adverse changes in body image including diminished feelings of femininity, sexuality and sexual satisfaction, and self-esteem can occur following a CPM [6,40-43]. Negative body image was also associated with high preoperative cancer distress [40]. In a survey of women who had undergone CPM, 42 percent stated that their sense of sexuality was worse than expected, and 31 percent felt that their self-consciousness about their appearance was also worse than expected [19]. However, 80 percent reported that they were "extremely confident in their decision to have CPM", and 90 percent would have made the same decision again [19].

The personal satisfaction following a CPM is reportedly high [43,44]. For example, a survey of 583 patients found that the majority (83 percent) of women were satisfied with the CPM 10 years after the operation, while 8 percent were neutral and 9 percent were dissatisfied [43]. However, 33 percent were dissatisfied with body appearance, 26 percent had adverse feelings of femininity, and 23 percent reported adverse sexual relationships.

Such a high level of satisfaction may be secondary to cognitive dissonance, a phenomenon documented in validated patient satisfaction measurements, and relevant to autonomous surgical decision-making when the decision is difficult to change [2,45-47].

Quality of life — Quality-of-life-related measures for women undergoing a CPM were comparable to women in the general population. In a prospective study of 60 women with breast cancer who had also undergone a CPM, most patients had a satisfactory health-related quality of life two years after the operation, with no difference in anxiety or depression [42].

In the meta-analysis discussed above, studies reported reduced anxiety regarding breast cancer relative to those who opted for surveillance [2]. (See 'Overall survival' above.)

OPERATIVE APPROACHES

Mastectomy with or without reconstruction — Typically, most patients are advised to undergo the same type of mastectomy (eg, skin-sparing, conventional) that is used for the mastectomy to treat the breast cancer. For women with mutations in breast cancer susceptibility gene 1 or 2 (BRCA1/2) or moderate-penetrance genes who are eligible for mastectomy, nipple-sparing mastectomy is a reasonable approach [48]. The type of mastectomy is determined by the tumor characteristics, patient body habitus, patient preference, and surgical expertise. There is no adverse impact of immediate reconstruction either in the development or detection of future cancers [49]. Reconstruction is determined by the use of postoperative radiation treatments, patient preference, and surgeon expertise.

Specific approaches to performing a mastectomy and breast reconstruction are discussed separately. (See "Mastectomy" and "Overview of breast reconstruction".)

Sentinel lymph node dissection — While there are differences of opinion, a sentinel lymph node dissection is not required when performing a CPM [28,29,50]. Some have argued that the risk of this minimally invasive procedure is small, and would preempt the need for axillary evaluation if an occult invasive cancer was found on final pathology [50]. Others, however, argue that the risk of finding metastatic disease warranting axillary staging in patients undergoing prophylactic mastectomy is low, and therefore sentinel node biopsy in these patients can be omitted [28]. (See "Overview of sentinel lymph node biopsy in breast cancer" and "Sentinel lymph node biopsy in breast cancer: Techniques".)

OTHER ASPECTS OF RISK REDUCTION — Most women with early breast cancer will be offered some type of adjuvant systemic therapy, the exception being possibly for those with very small "triple-negative" tumors (<0.5 cm). Systemic therapy may consist of chemotherapy, depending on the stage of the cancer and other prognostic and predictive features, human epidermal growth factor receptor 2 (HER2)-directed therapy for HER2-positive tumors, and endocrine therapy for hormone receptor-positive tumors. The decision to proceed with CPM does not affect these recommendations. For those with hormone receptor-positive, invasive tumors, adjuvant endocrine therapy has been shown to reduce the risk of breast cancer recurrence. Discussion of appropriate adjuvant therapy as well as medical risk-reducing strategies is found elsewhere. (See "Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer" and "Adjuvant systemic therapy for HER2-positive breast cancer" and "Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer" and "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

For those who do not proceed with CPM, breast cancer surveillance remains an important aspect of risk management. (See "Approach to the patient following treatment for breast cancer", section on 'Breast imaging'.)

SPECIAL CONSIDERATIONS

BRCA carriers — Breast cancer susceptibility gene 1 and 2 (BRCA1 AND BRCA2 [BRCA]) mutation carriers have a consistently documented increased risk of ipsilateral and contralateral breast cancer [12]. Therefore, even though breast conservation therapy appears to be an effective local treatment option in these patients [11,12,51,52], they may opt to undergo bilateral mastectomy to reduce their risk of a second breast cancer. CPM is an effective and popular option for reducing the risk of contralateral breast cancer recurrence, and evidence suggests that it may improve disease-free and overall survival [1,2,7,12,53,54]. It is important to note, however, that the absolute risk of contralateral breast cancer in mutation carriers diminishes significantly if their first breast cancer is diagnosed after age 50 [13].

The following studies illustrate the benefits of CPM among BRCA carriers with breast cancer:

In a retrospective analysis of 181 patients, a CPM was associated with a 48 percent reduction in death from breast cancer (hazard ratio [HR] 0.52, 95% CI 0.29-0.93) [3]. The 20-year survival rate for BRCA carriers undergoing a CPM was 88 percent compared with a 66 percent survival rate for carriers treated with a unilateral mastectomy.

A retrospective review and matched analysis of 105 women with breast cancer and a deleterious BRCA mutation undergoing a CPM had a greater ten-year survival compared with BRCA carriers with breast cancer who did not undergo a CPM (n = 593; 89 versus 71 percent) [34]. After adjusting for potential confounders, such as oophorectomy, grade and stage of cancer, and specific gene with the mutation, CPM continued to provide a survival advantage (HR 0.37, 95% CI 0.17-0.80).

Considerations during the COVID-19 pandemic — The COVID-19 pandemic has increased the complexity of cancer care. Important issues in areas where viral transmission rates are high include balancing the risk from treatment delay versus harm from COVID-19, ways to minimize negative impacts of social distancing during care delivery, and appropriately and fairly allocating limited health care resources. These and other recommendations for cancer care during active phases of the COVID-19 pandemic are discussed separately. (See "COVID-19: Considerations in patients with cancer".)

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: Hereditary breast and ovarian cancer" and "Society guideline links: Breast cancer".)

SUMMARY AND RECOMMENDATIONS

Introduction – Patients with a unilateral sporadic breast cancer are at a modest risk of developing an invasive contralateral breast cancer (CBC), and most women never will develop a contralateral second primary breast cancer. (See 'Introduction' above.)

Rationale – The rationale for contralateral prophylactic mastectomy (CPM) in a patient who has had breast cancer is to reduce the risk of CBC. Other reasons for undergoing a CPM include relative ease of follow-up without a mammogram or magnetic resonance imaging (MRI), reduction of anxiety for occurrence of a second breast cancer, and desire for symmetry that can be achieved with bilateral mastectomies and reconstruction. (See 'Rationale' above.)

Candidate selection – Risk-reduction mastectomy is often offered to patients with or without a previous history of breast cancer who carry a germline genetic mutation conferring a high risk for breast cancer (breast cancer susceptibility genes 1 and 2 [BRCA1/2], tumor protein p53 [TP53], phosphatase and tensin homolog [PTEN], cadherin 1 [CDH1], or serine/threonine protein kinase 11 [STK11] mutation), those with a strong family history of breast or ovarian cancer, and those with a history of thoracic radiation therapy at <30 years of age.

The decision to undergo a CPM is based on these same factors but is also individualized according to patient preferences and history, taking into account the surgical management of the presenting breast cancer (ie, mastectomy), the risk of contralateral disease given an ipsilateral cancer, and the patient’s desire for symmetry and anxieties regarding follow-up imaging. (See 'Candidate selection' above and 'Decision-making process' above.)

Breast cancer risk reduction – Women with breast cancer and a family history of breast or ovarian cancer and who undergo a CPM have a 96 percent reduction in risk of developing a contralateral cancer. (See 'Breast cancer risk reduction' above.)

Effect on overall survival – There is no clear overall survival benefit for most breast cancer patients who undergo a CPM, though prospective randomized data are unavailable. However, a survival benefit with CPM exists for patients with a deleterious BRCA1 or BRCA2 mutation, and possibly for those diagnosed at a young age (<50 years). (See 'Overall survival' above.)

Complications – Women with breast cancer undergoing a CPM have nearly a twofold increased risk of major complications (eg, reoperation) compared with women undergoing a unilateral mastectomy. (See 'Postoperative morbidity and mortality' above.)

Operative approaches – Typically, the same type of mastectomy is performed for a CPM as for the mastectomy to treat the breast cancer. (See 'Mastectomy with or without reconstruction' above and "Mastectomy".)

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  54. Boughey JC, Hoskin TL, Degnim AC, et al. Contralateral prophylactic mastectomy is associated with a survival advantage in high-risk women with a personal history of breast cancer. Ann Surg Oncol 2010; 17:2702.
Topic 94744 Version 22.0

References

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