Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy

Abstract

Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient’s age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.

Management and Clinical Outcomes of Breast Cancer in Women Diagnosed with Hereditary Cancer Syndromes in a Clinic-Based Sample from Colombia

“…Bilateral RRM confers a substantial reduction in breast cancer risk for unaffected individuals with PVs in BRCA1–2 genes, estimated at 90% and up to 95% when combined with RRSO [ 45 , 46 , 47 , 48 ]. Regarding mortality risk, a recent population-based cohort study reported that it was lower among unaffected individuals with PVs in the BRCA1 gene who underwent bilateral RRM compared to those under surveillance, though this effect was not observed in unaffected individuals with PVs in the BRCA2 gene [ 47 , 48 ]. The annualized cumulative incidence rate of contralateral breast cancer among unilateral breast cancer cases with germline PVs in BRCA1 and BRCA2 genes is 2.3% and 1.7% per year, respectively [ 49 , 50 ].…”

“…The annualized cumulative incidence rate of contralateral breast cancer among unilateral breast cancer cases with germline PVs in BRCA1 and BRCA2 genes is 2.3% and 1.7% per year, respectively [ 49 , 50 ]. Due to this increased risk, some may be considered for contralateral RRM, although the oncological benefits are not clear given that their prognosis is primarily dictated by their primary breast cancer [ 48 , 51 , 52 ]. This evidence underscores the need for more individualized counseling based on the BRCA variant type and the difficulties inherent in choosing between bilateral RRM and breast cancer surveillance among unaffected and affected carriers [ 47 , 48 ].…”