Coverage Policy Manual
Policy #: 1997133
Category: Surgery
Initiated: January 1994
Last Review: August 2022
  Risk-Reducing Mastectomy

Description:
Risk-reducing mastectomy is defined as the removal of the breast in the absence of malignant disease. Risk-reducing mastectomies may be considered in women considered at high risk of developing breast cancer, either due to a family history, presence of a BRCA1 or BRCA2 mutation, having received radiotherapy to the chest, or the presence of lesions associated with an increased cancer risk such as lobular carcinoma in situ. Therefore, bilateral risk-reducing mastectomy may be performed to eliminate the risk of cancer arising elsewhere; chemoprevention and close surveillance are alternative risk-reduction strategies. Risk-reducing mastectomies are typically bilateral, but can also describe a unilateral mastectomy in a patient who has previously undergone or is currently undergoing a mastectomy in the opposite breast for an invasive cancer (i.e. contralateral risk-reducing mastectomy). Use of contralateral risk-reducing mastectomy has increased in the U.S. An analysis of data from the National Cancer Database found that the rate of contralateral risk-reducing mastectomy in women diagnosed with unilateral stage I, II, or III breast cancer increased from approximately 4% in 1998 to 9.4% in 2002 (Yao, 2013). Another analysis of data from the National Cancer Database (N=765,487) found that individuals with unilateral stage I breast cancer commonly underwent contralateral risk-reducing mastectomy with an increase between 2006 (6%) and 2016 (9%) (Baskin, 2021).
 
Two types of risk-reducing mastectomies can be performed:
 
    1. total (also referred to as simple) mastectomy, in which the intent is to remove the entire breast and nipple areolar complex
    2. subcutaneous mastectomy, where the nipple areolar complex is left intact for a more natural appearance.
 
While breast tissue is certainly left behind in a subcutaneous mastectomy, residual breast tissue in the axillary tail and skin flaps may be identified after a total mastectomy. However, from a purely prophylactic standpoint, a total mastectomy is generally preferred over a subcutaneous mastectomy because there is less residual breast tissue.
 
The appropriateness of a risk-reducing mastectomy is a complicated risk-benefit analysis that requires estimates of a patient’s risk of breast cancer, typically based on the patient’s family history of breast cancer and other factors. Several models are available to assess risk of breast cancer (McCarthy, 2020). The specific risk factors included in the models vary, but all incorporate characteristics related to age, reproductive history, and family history. Race should also be considered when assessing risk. According to an analysis of the Surveillance, Epidemiology, and End Results program (SEER) from 2000 to 2015 (N=459,916), the risk of invasive contralateral breast cancer was higher in Black (hazard ratio, 1.44; 95% confidence interval, 1.35 to 1.54) and Hispanic individuals (hazard ratio, 1.11; 95% confidence interval, 1.02 to 1.20) compared to Whites (Watt, 2021). In addition to the patient's risk assessment, the choice of a risk-reducing mastectomy is based on patient tolerance for risk, consideration of changes to appearance and need for additional cosmetic surgery, and the risk-reduction offered by mastectomy versus other options.

Policy/
Coverage:
Effective July 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Risk reducing mastectomy and subcutaneous mastectomy meets primary coverage criteria for effectiveness and is covered in patients at high risk* or moderately** increased risk of breast cancer.
 
Risk reducing mastectomy meets primary coverage criteria for effectiveness and is covered in patients with such extensive mammographic abnormalities (ie, calcifications) that adequate biopsy or excision is impossible.
 
 
*High risk of breast cancer may be defined as one or more of the following:
 
    • Lobular carcinoma in situ or  
    • Two or more first degree relatives with breast cancer;
    • One first-degree relative and two or more second-degree or third-degree relatives with breast cancer;
    • One first-degree relative with breast cancer before the age of 45 years and one other relative with breast cancer;
    • One first-degree relative with breast cancer and one or more relatives with ovarian cancer;
    • Two second-degree or third-degree relatives with breast cancer and one or more with ovarian cancer;
    • One second-degree or third-degree relative with breast cancer and two or more with ovarian cancer;
    • Three or more second-degree or third-degree relatives with breast cancer;
    • One first-degree relative with bilateral breast cancer;
    • Presence of a BRCA1 or BRCA2 mutation in the patient consistent with a BRCA 1 or 2 mutation in a family member with breast or ovarian cancer;
    • Presence of a TP53 or PTEN mutation;  
    • Another gene mutation associated with increased risk (eg, PTEN, TP53, CDH1 and STK11) or
    • Has received radiation therapy to the chest between ages of 10 - 30 years.  
 
**Patients at moderately increased risk of breast cancer may be identified as follows:
    • Women who do not meet the definition of high risk, but nonetheless are considered at moderately increased risk are those with atypical hyperplasia or cancer in the opposite breast;
    • Patients with such extensive mammographic abnormalities (i.e., calcifications) that adequate biopsy is impossible.
 
It is recommended that all candidates for risk reducing mastectomy consider undergoing counseling from a health professional skilled in assessing cancer risk (from someone in addition to the operating surgeon). Cancer risk should be assessed by performing a complete family history, use of the Gail or Claus model to estimate the risk of cancer, and discussion of the various treatment options, including increased surveillance or chemoprevention with tamoxifen.
 
Does Not Meet Primary Coverage Criteria Or Is Not Covered For Contracts Without Primary Coverage Criteria
 
Risk reducing mastectomy in any other situation does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, risk reducing mastectomy in any other situation is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior to July 2018
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Prophylactic simple mastectomy and subcutaneous mastectomy meets primary coverage criteria for effectiveness and is covered in patients at high risk* or moderately** increased risk of breast cancer.
 
Prophylactic mastectomy meets primary coverage criteria for effectiveness and is covered in patients with such extensive mammographic abnormalities (ie, calcifications) that adequate biopsy or excision is impossible.
 
 
*High risk of breast cancer may be defined as one or more of the following:
    • Lobular carcinoma in situ or
    • Two or more first degree relatives with breast cancer;
    • One first-degree relative and two or more second-degree or third-degree relatives with breast cancer;
    • One first-degree relative with breast cancer before the age of 45 years and one other relative with breast cancer;
    • One first-degree relative with breast cancer and one or more relatives with ovarian cancer;
    • Two second-degree or third-degree relatives with breast cancer and one or more with ovarian cancer;
    • One second-degree or third-degree relative with breast cancer and two or more with ovarian cancer;
    • Three or more second-degree or third-degree relatives with breast cancer;
    • One first-degree relative with bilateral breast cancer;
    • Presence of a BRCA1 or BRCA2 mutation in the patient consistent with a BRCA 1 or 2 mutation in a family member with breast or ovarian cancer;
    • Presence of a TP53 or PTEN mutation;
    • another gene mutation associated with increased risk (eg, PTEN, TP53, CDH1 and STK11) or
    • Has received radiation therapy to the chest between ages of 10 - 30 years.
 
**Patients at moderately increased risk of breast cancer may be identified as follows:
    • Women who do not meet the definition of high risk, but nonetheless are considered at moderately increased risk are those with atypical hyperplasia or cancer in the opposite breast;
    • Patients with such extensive mammographic abnormalities (i.e., calcifications) that adequate biopsy is impossible.
 
It is recommended that all candidates for prophylactic mastectomy consider undergoing counseling from a health professional skilled in assessing cancer risk (from someone in addition to the operating surgeon). Cancer risk should be assessed by performing a complete family history, use of the Gail or Claus model to estimate the risk of cancer, and discussion of the various treatment options, including increased surveillance or chemoprevention with tamoxifen.
 
Meets Primary Coverage Criteria Or Is Covered For Contracts Without Primary Coverage Criteria
 
Prophylactic mastectomy in any other situation does not meet member benefit certificate primary coverage criteria. For members with contracts without primary coverage criteria, prophylactic mastectomy in any other situation is considered investigational. Investigational services are specific contract exclusions in most member benefit certificates of coverage.
 
Effective Prior To August 2017
Prophylactic simple mastectomy meets primary coverage criteria for effectiveness and is covered in patients at high risk or moderately increased risk of breast cancer.
 
Prophylactic mastectomy meets primary coverage criteria for effectiveness and is covered in patients with such extensive mammographic abnormalities (ie, calcifications) that adequate biopsy or excision is impossible.
 
High risk of breast cancer may be defined as one or more of the following:
  • Lobular carcinoma in situ or
  • Two or more first degree relatives with breast cancer;
  • One first-degree relative and two or more second-degree or third-degree relatives with breast cancer;
  • One first-degree relative with breast cancer before the age of 45 years and one other relative with breast cancer;
  • One first-degree relative with breast cancer and one or more relatives with ovarian cancer;
  • Two second-degree or third-degree relatives with breast cancer and one or more with ovarian cancer;
  • One second-degree or third-degree relative with breast cancer and two or more with ovarian cancer;
  • Three or more second-degree or third-degree relatives with breast cancer;
  • One first-degree relative with bilateral breast cancer;
  • Presence of a BRCA1 or BRCA2 mutation in the patient consistent with a BRCA 1 or 2 mutation in a family member with breast or ovarian cancer;
  • Presence of a TP53 or PTEN mutation;
  • another gene mutation associated with increased risk (eg, PTEN, TP53, CDH1 and STK11) or  
Has received radiation therapy to the chest between ages of 10 - 30 years.
 
Patients at moderately increased risk of breast cancer may be identified as follows:
    • Women who do not meet the definition of high risk, but nonetheless are considered at moderately increased risk are those with atypical hyperplasia or cancer in the opposite breast;
    • Patients with such extensive mammographic abnormalities (i.e., calcifications) that adequate biopsy is impossible.
 
It is recommended that all candidates for prophylactic mastectomy consider undergoing counseling from a health professional skilled in assessing cancer risk (from someone in addition to the operating surgeon). Cancer risk should be assessed by performing a complete family history, use of the Gail or Claus model to estimate the risk of cancer, and discussion of the various treatment options, including increased surveillance or chemoprevention with tamoxifen.
 
Subcutaneous mastectomy leaves larger amounts of glandular tissue and is not covered for prophylaxis based on Primary Coverage Criteria for effectiveness.

Rationale:
In 1999 Hartmann et al. reported a  retrospective cohort analysis of 639 women with a family history of breast cancer who underwent bilateral prophylactic mastectomy between 1960 and 1993 at the Mayo Clinic.  A total of 90% of the mastectomies were subcutaneous. The patients were subdivided into 2 groups: high-risk patients had a family history suggestive of hereditary breast cancer (n=214), while the remaining 425 patients were arbitrarily considered to have a moderately increased risk. However, it should be emphasized that all women had some sort of family history of breast cancer. For each group, the reduction in the incidence of a mortality due to breast cancer was estimated by comparison to a control group (sisters of high-risk patients) or predicted outcomes (using the Gail model for moderate-risk patients).
 
For patients at moderate risk of breast cancer, 37.4 cancers were predicted by the Gail model, and 4 were observed for an incidence reduction of 89.5%. Approximately 13 women would have to have prophylactic mastectomy to prevent 1 cancer. For those at high risk of breast cancer, reduction in breast cancer incidence ranged from 90%–94%. Four to 8 women would need to undergo prophylactic mastectomy to prevent 1 occurrence of breast cancer.
 
While all patients in the Hartmann study had a family history of breast cancer, one should not conclude that all patients with a family history of breast cancer are candidates for a prophylactic mastectomy. Essentially the decision is a complicated patient-driven risk-benefit analysis of the individual cancer risk. While the cancer risk is greatest for those considered at high risk, whether or not the cancer risk associated with moderate-risk patients warrants a prophylactic mastectomy is a difficult question. While high risk is more objectively defined either by a family history alone or the presence of a BRCA1 or BRCA2 mutation, moderate risk may be conferred by a wide range of family histories in association with different breast pathologies.
 
The Gail model has been used as a patient selection criteria to identify women at increased risk of breast cancer who would be candidates for chemoprevention with tamoxifen. The Breast Cancer Chemoprevention Trial (Fisher, 1998) accepted patients between the ages of 35 and 59 years with a 5-year predicted risk of breast cancer of 1.66%, according to the Gail model.  Presumably, at the very least, the predicted cancer risk for candidates for prophylactic mastectomy should exceed that of candidates for chemoprevention.
 
In 2001 Meijers-Heijboer et al reported a prospective study of 139 women with a pathogenic BRCA1 or BRCA2 mutation.  Seventy-six women had prophylactic mastectomy while 63 remained under regular surveillance.  No cases of breast cancer were observed in the prophylactic mastectomy group after a mean follow-up of 2.9+/-1.4 years.  Eight breast cancers developed in the surveillance group after a mean follow-up of 3.0+/-1.5 years.  In 2007 Heemskerk-Gerritsen reported 358 high risk women (236 BRCA1/2 carriers) who underwent prophylactic mastectomy.  Of these 358 women 177 were unaffected with breast cancer and 181 had breast cancer.  No primary breast cancers occurred after primary mastectomy within a median follow-up of 4.5 years.
 
Wahner-Roedler (2003) reported on a review of medical records of 653 female patients who received supradiaphragmatic radiation therapy for Hodgkin's lymphoma at the Mayo Clinic.  Four patients had breast cancer diagnosed before the lymphoma was discovered and were not included in the review. The median age of patients receiving supradiaphragmatic radiation was 31.8 years with a median duration of follow-up of 8.7 years.  Thirty patients subsequently developed breast cancer (4 with bilateral disease).  Breast cancer risk signifcantly increased 15 to 30 years after patients received radiation therapy and risk was inversely related to age at the time of radiation therapy until 30 years. The standardized morbidity ratio for patients younger than 30 years at supradiaphragmatic radiation therapy was 8.5 (95% CI, 53-13.1) vs 1.2 (95% CI, 0.5-2.2) for those aged 30 years or older.  Splenectomy increased breast cancer risk (P = .01).
 
Herrinton et al. (2005) identified 56,400 women diagnosed with unilateral breast cancer during 1997 to 1999 using cancer registries from six HMOs, members of the Cancer Research Network.  Contralateral prophylactic mastectomy was performed in 1,072 (1.9%) of those women.  Of these, 133 women were diagnoses with a new or recurrent breast cancer 60 days or more after CPM and five (0.5%) developed a contralateral breast cancer.  Among the four HMOs used in the mortality analysis 74 (8.1%) for 908 women in the CPM group and 5,437 (11.7%) of the non-CPM group died of breast cancer.  
 
Tuttle et al. (2007) reviewed treatment of patients diagnosed with unilateral breast cancer diagnosed from 1998 through 2003.  The contralateral prophylactic mastectomy rate increased from 4.2% in 1998 to 11.0% in 2003.  They concluded there was a critical need for prospective studies to understand the decision-making processes that have led to more aggressive breast cancer surgery.
 
2011 Update
A search of the Medline database was conducted through January 2011.  There was no new literature identified that would prompt a change in the coverage statement.
 
An updated Cochrane review was published by Lostumbo and colleagues in 2010. The 39 included studies were observational studies with some methodological limitations. There were no randomized trials. The studies presented data on 7,384 women with a wide range of risk factors for breast cancer who underwent prophylactic mastectomy (PM). Bilateral prophylactic mastectomy (BPM) studies on the incidence of breast cancer and/or disease-specific mortality reported reductions after BPM particularly for those with BRCA1/2 mutations. For contralateral prophylactic mastectomy (CPM), studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Sixteen studies assessed psychosocial measures; most of these reported high levels of satisfaction with the decision to have PM but more variable satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BPM when compared to baseline worry levels. Case series reporting on adverse events from PM with or without reconstruction reported rates of unanticipated re-operations from 4% in those without reconstruction to 49% in patients with reconstruction. The authors’ summary and conclusions are as follows: “Sixteen observational studies have been published since the last version of the review, without altering our conclusions. While published observational studies demonstrated that bilateral prophylactic mastectomy (BPM) was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies (ideally randomized trials) are needed. BPM should be considered only among those at very high risk of disease. There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival and studies that control for multiple confounding variables are needed.”
 
2012 Update
A literature review conducted through January 2012 did not identify any new information that would prompt a change in the coverage statement.
 
A search of online site ClinicalTrials.gov in January 2012 found one registry study of prophylactic mastectomy for breast cancer risk reduction. This registry will examine patient quality of life, cancer occurrence, adverse events, and survival annually for 10 years (NCT00555503).
 
2013 Update
A literature search through February 2013 did not reveal any new evidence that would prompt a change in the coverage statement.
 
 
2014 Update
A literature search was conducted using the MEDLINE database through February 2014. No information was identified that would prompt a change in the coverage statement. Two studies evaluating the impact on health outcomes were identified.
 
In 2013, Yao et al evaluated overall survival after CPM by analyzing data from the National Cancer Data Base (Yao, 2013). The database collects data from 1450 Commission of Cancer-accredited cancer programs. The analysis included 219,983 women who had mastectomy for unilateral breast cancer; 14,994 (7%) of these women underwent CPM at the time of their mastectomy surgery. The overall 5-year survival rate was 80%. In an analysis adjusting for confounding factors, the risk of death was significantly lower in women who had CPM compared with women who did not have CPM. The adjusted hazard ratio (HR) was 0.88 (95% confidence interval [CI], 0.83 to 0.93). The absolute risk of death over 5 years with CPM was 2.0% lower than without CPM. In subgroup analyses, a survival benefit after CPM was found for individuals age 18 to 49 years and age 50 to 69 years, but not in patients 70 years or older. There was a survival benefit for women with stage I and II tumors, but not stage III tumors. Data were not available to do subgroup analyses according to the presence or absence of genetic mutations or family history risk factors.
 
Also in 2013, a study by Miller et al evaluated potential risks associated with CPM at a single institution (Miller, 2013). Among 600 women treated for unilateral breast cancer, 391 (65%) underwent unilateral mastectomy and 209 (35%) underwent CPM. CPM patients tended to be diagnosed at an earlier stage than unilateral mastectomy patients and were less likely to undergo adjuvant therapy. A total of 402 patients underwent immediate reconstruction surgery, 55% of the unilateral mastectomy group and 90% of the CPM group. Overall, CPM patients had significantly more operative complications (112, 41.6%) than unilateral mastectomy patients (87, 28.6%), p<0.001. Moreover, there were more major complications in the CPM group. Twenty-nine (13.9%) patients in the CPM group and 16 (4.1%) patients in the unilateral mastectomy group experienced major complications, p=0.001. The most frequent major complications were fixed tissue expander or implant control (CPM patients) and seroma requiring reoperation in unilateral mastectomy patients. In multivariate analysis controlling for type of reconstruction and other factors such as adjuvant therapy, age, etc., CPM remained associated with a significantly higher risk of any complication (odds ratio [OR]=1.53, 95% CI, 1.04 to 2.25) and a significantly higher risk of major complications (OR=2.66, 95% CI, 1.37 to 5.19).
 
2015 Update
A literature search conducted through February 2015 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Contralateral Prophylactic Mastectomy
Several observational analyses with large numbers of patients have been published. The study with the largest sample size was a 2014 systematic review and meta-analysis by Fayanju and colleagues (Fayanju, 2014). The authors searched for published studies that compared the incidence of contralateral breast cancer in women with unilateral disease who did and did not undergo contralateral prophylactic mastectomy (CPM). The investigators did not differentiate between women who did and did not have risk factors such as certain genetic mutations or syndromes. Fourteen studies met eligibility criteria and were included in the metaanalysis; none were RCTs. In a meta-analysis of data from 6 studies, overall survival (OS) was significantly higher in the patients who underwent CPM (n=10,666) than those who had no CPM
(n=145,490), relative risk (RR), 1.09 (95% confidence interval [CI], 1.06 to 1.11). Moreover, mortality from breast cancer was lower in the group that had CPM (RR, 0.69, 95% CI, 0.56 to 0.85, 4 studies).
However, CPM was not associated with a reduction in the absolute risk of metachronous contralateral breast cancer (risk difference [RD], -18%, 95% CI, -42.0% to 5.9%, 8 studies). The authors commented that the improvement in survival after CPM in the general breast cancer population is likely not due to a decreased incidence of CBC, but rather is secondary to selection bias (eg, CPM recipients may be otherwise healthier and have better access to health care). Other analyses have also concluded that the association between CPM and reduced mortality identified in data analyses can be attributed at least in part to selection of a healthier cohort of women for CPM (Kruper, 2014; Jatoi, 2014).
 
A study by Pesce and colleagues, focused on the subgroup of patients who were young (<45 years-old) with stage I or II breast cancer (Pesce, 2014). A total of 4338 of 10,289 women in this subgroup (29.7%) had CPM at the time of mastectomy surgery. Median follow-up was 6.1 years. In a multivariate analysis controlling for potentially confounding factors, OS did not differ significantly among patients who underwent unilateral mastectomy and those who additionally had CPM (HR, 0.93, 95% CI, 0.79 to 1.09). Moreover, among women younger than 45 years-old with estrogen-receptor negative cancer, there was no significant improvement in OS in those who underwent CPM versus unilateral mastectomy (HR, 1.13, 95% CI, 0.90 to 1.42).
 
Eck and colleagues reported on 352 patients undergoing mastectomy for unilateral breast cancer (Eck, 2014).  Within this cohort, 205 patients (58%) had unilateral mastectomy and 147 (42%) had bilateral mastectomy. A total of 94 women (27%) had complications, 48 (23%) in the unilateral mastectomy group and 46 (31%) in the bilateral mastectomy group, p=0.11. Morbidity occurred only in the prophylactic breast in 19 women (13% of those undergoing CPM); 10 of these patients required reoperation. Women with complications had a longer time before receiving adjuvant therapy compared with those without complications (49 days vs 40 days, p<0.001).
 
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in December 2014 did not identify any ongoing RCTs or large observational studies.
 
Practice Guidelines and Position Statements
 
National Comprehensive Cancer Network
  • Breast Cancer Risk Reduction, 2014 (V.1) “Risk-reduction mastectomy should generally be considered only in women with a genetic mutation conferring a high risk history for breast cancer (BRCA 1/2, PTEN, TP53, CDH1, STK11), compelling family history, or possibly with LCIS or prior thoracic radiation therapy at < 30 years of age. The value of risk-reduction mastectomy in women with deleterious mutations in other genes associated with a 2-fold or greater risk for breast cancer (based on large epidemiologic studies) in the absence of a compelling family history of breast cancer is unknown.” (NCCN, 2014a)
  • Breast cancer, 2014 (V.3) Except for certain high-risk situations (noted in the risk reduction guideline previously discussed), CPM is discouraged (NCCN, 2014b)  The guideline states, “the small benefits from  ontralateral prophylactic mastectomy for women with unilateral breast cancer must be balanced with the risk of recurrent disease from the known ipsilateral breast cancer, psychological and social issues of bilateral mastectomy, and the risks of contralateral mastectomy. The use of a prophylactic mastectomy contralateral to a breast treated with breast conserving therapy is very strongly discouraged.”
     
2016 Update
A literature search conducted through February 2016 did not reveal any new information that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Ongoing and Unpublished Clinical Trials
A search of ClinicalTrials.gov in January 2016 did not identify any ongoing or unpublished trials that would likely influence this review.
 
2018 Update
Annual policy review completed with a literature search using the MEDLINE database through July 2018. No new literature was identified that would prompt a change in the coverage statement.
 
2019 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2019. No new literature was identified that would prompt a change in the coverage statement.
 
2020 Update
A literature search was conducted through June 2020.  There was no new information identified that would prompt a change in the coverage statement.  
 
2021 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2021. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
A Cochrane review by Carbine et al examined the impact of risk-reducing mastectomy on mortality and other health outcomes (Carbine, 2018). Reviewers did not identify any RCTs. Sixty-one observational studies with some methodologic limitations were identified. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer who underwent a risk-reducing mastectomy. Studies on the incidence of breast cancer and/or disease-specific mortality (n=21) reported reductions in both after a bilateral risk-reducing mastectomy, particularly for those with BRCA1 or BRCA2 variants.
 
The previously summarized Cochrane review by Carbine et al also assessed various outcomes, including mortality and disease-free survival, among women who received a contralateral risk-reducing mastectomy (Carbine, 2018). Twenty-six observational studies assessed outcomes in women who received contralateral risk-reducing mastectomy. While results showed a reduced incidence CBC among women who received a contralateral risk-reducing mastectomy, results on disease-specific mortality were inconsistent. Seven of the included studies showed no survival advantage. One additional study showed an improvement in all-cause mortality associated with contralateral risk-reducing mastectomy; however, significance was lost after adjustment for bilateral risk-reducing salpingo-oophorectomy. The authors attributed the variability in mortality findings, in part, to selection bias, since younger, healthier women may be more likely to opt for contralateral risk-reducing mastectomy.
 
An analysis of 17 years of SEER data from 245,418 women in California with unilateral breast cancer assessed secondary contralateral cancer incidence and mortality in women who had bilateral mastectomy or breast conserving therapy (Kurian, 2020). The study adjusted for numerous potential confounders, including demographic and socioeconomic characteristics, clinical characteristics and disease state, and year of diagnosis. After a median 7 year follow-up, the study found that when compared with breast conserving therapy that included radiotherapy, bilateral mastectomy was associated with a reduced risk of secondary breast cancer (HR, 0.11; 95% CI, 0.07 to 0.14) while unilateral mastectomy was associated with increased risk (HR, 1.07; 95% CI, 1.02 to 1.13). However, the study also found bilateral mastectomy was not associated with a significant reduction in breast cancer-related mortality relative to breast-conserving therapy (HR, 1.03; 95% CI, 0.96 to 1.11).
 
Schroeder et al conducted a population-based study of 12,959 women who underwent unilateral mastectomy or contralateral risk-reducing mastectomy using data from the New York Statewide Planning and Research Cooperative System (Schroeder, 2020). Of these, 1,384 underwent a contralateral risk-reducing mastectomy and 11,575 underwent a unilateral mastectomy. After controlling for confounding factors (ie, race, ethnicity, year of operation, and type of insurance) and stratifying by breast reconstruction, no difference was found in the likelihood of complications or additional breast-related procedures needed between women who received contralateral risk-reducing mastectomy and those who received unilateral mastectomy (both without breast reconstruction). Addition of breast reconstruction was associated with significant increases in complications and breast-related procedures, both in women with unilateral mastectomy (odds ratio [OR], 3.6; p<.001 and OR, 13.7; p<.001, respectively) and in those with contralateral risk-reducing mastectomy (OR, 3.3; p<.001 and OR, 30.1; p<.001, respectively). Patients who underwent contralateral risk-reducing mastectomy were also significantly more likely to undergo breast reconstruction compared to those who underwent unilateral mastectomy (93.1% vs. 46.3%; p<.001).
In 2020, the American Society for Clinical Oncology, American Society for Radiation Oncology, and Society of Surgical Oncology published joint guidelines on management of hereditary breast cancer (Tung, 2020). The guideline discusses management of patients with breast cancer with germline mutations in breast cancer susceptibility genes (eg, BRCA1/2, ATM, TP53) and makes the following recommendations regarding risk-reducing mastectomy:
 
"Surgical management of the index malignancy (... contralateral risk-reducing mastectomy [CRRM]) in BRCA1/2 mutation carriers should be discussed, considering the increased risk of CBC and possible increased risk of an ipsilateral new primary breast cancer compared with noncarriers (Type: formal consensus; Evidence quality: intermediate; Strength of recommendation: strong)."
 
"For women with breast cancer who have a BRCA1/2 mutation and who have been treated or are being treated with unilateral mastectomy, CRRM should be offered. CRRM is associated with a decreased risk of CBC; there is insufficient evidence for improved survival." "Decisions regarding risk-reducing mastectomy (bilateral or contralateral) are highly personal and must be individualized for every patient. Studies show that women who opt for prophylactic mastectomy report positive outcomes, including decreased concern about developing breast cancer. This benefit must be weighed against possible problems with implants or reconstructive therapy and potential adverse feelings related to body image, femininity, and sexuality. Most patients who opt for prophylactic mastectomy demonstrate satisfaction with their decision."
 
"For women with breast cancer who have a mutation in a moderate-penetrance breast cancer predisposition gene and who have been treated or are being treated with unilateral mastectomy, the decision regarding [contralateral risk-reducing mastectomy] CRRM should not be based predominantly on mutation status. Additional factors that predict CBC such as age at diagnosis and family history should be considered, as they are in all cases. The impact of CRRM on decreasing risk of CBC is dependent on the risk of CBC for each individual gene. Data regarding the risk of CBC resulting from moderate-penetrance genes are limited (Type: formal consensus; Evidence quality: low; Strength of recommendation: moderate)."
 
The guideline also provides recommendations for assessing the risk of CBC and role of risk-reducing mastectomy in BRCA1/2 mutation carriers (Evidence quality: low; Strength of recommendation: moderate) and in women with breast cancer who have a BRCA1/2 mutation who have been treated or are being treated with unilateral mastectomy when considering contralateral risk-reducing mastectomy (Evidence quality: intermediate; Strength of recommendation: moderate). The guideline recommends consideration of the following:
 
    • Age at diagnosis (the strongest predictor of future CBC)
    • Family history of breast cancer
    • Overall prognosis from this or other cancers (eg, ovarian)
    • Ability of patient to undergo appropriate breast surveillance (magnetic resonance imaging [MRI])
    • Comorbidities
    • Life expectancy.
 
2022 Update
Annual policy review completed with a literature search using the MEDLINE database through June 2022. No new literature was identified that would prompt a change in the coverage statement. The key identified literature is summarized below.
 
Yang et al (2021) conducted an analysis of SEER data from 1998 to 2016 of 5118 men with unilateral breast cancer who underwent contralateral risk-reducing mastectomy (n=209 [4.1%]) (Yang, 2021). Patient race/ethnicity was mostly White (82.3%), followed by Black (12.4%), and other races (4.8%). In 1998, contralateral risk-reducing mastectomy was undertaken in 1.7% of men compared to 6.3% in 2016 (p<.0001). Compared to unilateral mastectomy, contralateral risk-reducing mastectomy improved OS (HR, 0.58; 95% CI, 0.37 to 0.89) but a survival benefit was not seen after propensity score-matching (HR, 0.83; 95% CI, 0.46 to 1.52). Contralateral risk-reducing mastectomy did not improve disease-specific survival compared to unilateral mastectomy.
 
In 2021, the American College of Genetics and Genomics published a guideline on management of individuals withPALB2 variants, which recommends that risk-reducing mastectomy be considered as an option based on personal risk (Tischkowitz, 2021).

CPT/HCPCS:
19303Mastectomy, simple, complete
19304Mastectomy, subcutaneous

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