Risk-reducing mastectomy for the prevention of primary breast cancer

Recent progress in understanding the genetic basis of breast cancer and widely publicized reports of celebrities undergoing risk-reducing mastectomy (RRM) have increased interest in RRM as a method of preventing breast cancer. This is an update of a Cochrane Review first published in 2004 and previously updated in 2006 and 2010.

(i) To determine whether risk-reducing mastectomy reduces death rates from any cause in women who have never had breast cancer and in women who have a history of breast cancer in one breast, and (ii) to examine the effect of risk-reducing mastectomy on other endpoints, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes.

For this Review update, we searched Cochrane Breast Cancer's Specialized Register, MEDLINE, Embase and the WHO International Clinical Trials Registry Platform (ICTRP) on 9 July 2016. We included studies in English.

Participants included women at risk for breast cancer in at least one breast. Interventions included all types of mastectomy performed for the purpose of preventing breast cancer.

At least two review authors independently abstracted data from each report. We summarized data descriptively; quantitative meta-analysis was not feasible due to heterogeneity of study designs and insufficient reporting. We analyzed data separately for bilateral risk-reducing mastectomy (BRRM) and contralateral risk-reducing mastectomy (CRRM). Four review authors assessed the methodological quality to determine whether or not the methods used sufficiently minimized selection bias, performance bias, detection bias, and attrition bias.

All 61 included studies were observational studies with some methodological limitations; randomized trials were absent. The studies presented data on 15,077 women with a wide range of risk factors for breast cancer, who underwent RRM.Twenty-one BRRM studies looking at the incidence of breast cancer or disease-specific mortality, or both, reported reductions after BRRM, particularly for those women with BRCA1/2 mutations. Twenty-six CRRM studies consistently reported reductions in incidence of contralateral breast cancer but were inconsistent about improvements in disease-specific survival. Seven studies attempted to control for multiple differences between intervention groups and showed no overall survival advantage for CRRM. Another study showed significantly improved survival following CRRM, but after adjusting for bilateral risk-reducing salpingo-oophorectomy (BRRSO), the CRRM effect on all-cause mortality was no longer significant.Twenty studies assessed psychosocial measures; most reported high levels of satisfaction with the decision to have RRM but greater variation in satisfaction with cosmetic results. Worry over breast cancer was significantly reduced after BRRM when compared both to baseline worry levels and to the groups who opted for surveillance rather than BRRM, but there was diminished satisfaction with body image and sexual feelings.Seventeen case series reporting on adverse events from RRM with or without reconstruction reported rates of unanticipated reoperations from 4% in those without reconstruction to 64% in participants with reconstruction.In women who have had cancer in one breast, removing the other breast may reduce the incidence of cancer in that other breast, but there is insufficient evidence that this improves survival because of the continuing risk of recurrence or metastases from the original cancer. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention, when considering RRM.

While published observational studies demonstrated that BRRM was effective in reducing both the incidence of, and death from, breast cancer, more rigorous prospective studies are suggested. BRRM should be considered only among those at high risk of disease, for example, BRCA1/2 carriers. CRRM was shown to reduce the incidence of contralateral breast cancer, but there is insufficient evidence that CRRM improves survival, and studies that control for multiple confounding variables are recommended. It is possible that selection bias in terms of healthier, younger women being recommended for or choosing CRRM produces better overall survival numbers for CRRM. Given the number of women who may be over-treated with BRRM/CRRM, it is critical that women and clinicians understand the true risk for each individual woman before considering surgery. Additionally, thought should be given to other options to reduce breast cancer risk, such as BRRSO and chemoprevention when considering RRM.