TOPLINE:

Risk-reducing mastectomy (RRM) in women with germline pathogenic variants (gPVs) in BRCA1 or BRCA2 (BRCA1/2) is associated with very low rates of subsequent breast cancer and surgical complications. Among 507 women who underwent RRM, only one developed breast cancer during a median follow-up of 8.6 years compared with 112 of 701 women who did not undergo RRM during a median follow-up of 4.4 years.

METHODOLOGY:

• Multiple guidelines recommend intensified surveillance with annual breast imaging and risk-reducing salpingo-oophorectomy for women with gPVs in BRCA1/2. Long-term follow-up studies regarding the safety of RRM in terms of cancer risk and surgical complications among women with gPVs in BRCA1/2 are scarce.
• Researchers conducted a nationwide cohort study in Sweden involving 1208 women with confirmed gPVs in BRCA1/2 without previous breast cancer, identified through Swedish Cancer Genetic Units between March 31, 1994, and January 2, 2019.
• Participants were divided into two groups: 507 women who underwent RRM (median age at RRM, 39.7 years; range, 19.6-72.1 years) and 701 women who did not undergo RRM (median age at genetic testing, 50.6 years; range, 4.3-93.6 years).
• Data were extracted from the National Patient Care Register, the Cancer Register, and the Cause of Death Register, with follow-up until breast cancer diagnosis, death, emigration, or December 31, 2023.
• Breast cancer incidence was calculated per 10,000 person-years, with women undergoing RRM contributing person-years to the no-RRM group until RRM, and women with occult breast cancer contributing breast cancer cases to the no-RRM group.
• Major surgical postoperative complications (msPOCs) were defined as prespecified surgical procedure codes for bleeding, wound, infectious, and/or unspecified complications within 30 days of RRM.

TAKEAWAY:

• In the RRM group, breast cancer incidence was two cases per 10,000 person-years (1 of 507 women developed breast cancer) compared with 162 cases per 10,000 person-years in the no-RRM group (112 of 701 women developed breast cancer).
• Occult breast cancer was identified in 17 of 507 women (3.4%) at the time of RRM, with 5 of 20 (25.0%) being invasive breast cancer, 14 of 20 (70.0%) being ductal carcinoma in situ, and 1 of 20 (5.0%) being Paget disease.
• Early msPOCs associated with reoperation occurred in 19 of 507 women (3.7%), including bleeding complications in 15 of 507 women (3.0%), wound complications in 1 of 507 women (0.2%), and infectious complications in 2 of 507 women (0.4%).
• The median age at RRM was 9.9 years older among women with occult cancer than among women without occult cancer (49.0 years [range, 31.7-63.9 years] vs 39.1 years [range, 19.6-72.1 years]; P = .003).

IN PRACTICE:

“In this cohort study of 1208 women with a gPV in BRCA1/2, the risk of developing breast cancer or early major surgical complications after RRM was very low,” wrote the authors of the study.

SOURCE:

The study was led by Rebecca Wiberg, MD, PhD, Department of Diagnostics and Intervention, Plastic Surgery and Surgery, Umeå University, Umeå, Sweden. It was published online on April 3 in JAMA Network Open.

LIMITATIONS:

The study has several limitations. Although the coverage of BRCA1/2 gPV carriers was high, it does not completely correspond to all women without breast cancer with identified gPVs in BRCA1/2 in Sweden because some predictive testing is performed at local laboratories. The topographic Cancer Register code 170 (International Classification of Diseases, Seventh Revision) does not distinguish between invasive and some preinvasive lesions, which may have led to incorrect classification of women with lobular carcinoma in situ when creating the study population. The no-RRM group retained heterogeneity in follow-up time, including women not undergoing RRM as well as women undergoing RRM until the date of surgery. Relatively low numbers of skin-sparing mastectomies and nipple-sparing mastectomies were reported, which might not fully mirror reality because the type of RRM was based on surgical procedure codes rather than a review of medical records. The msPOCs reported were based on surgical procedure codes and not diagnosis codes, limiting the complications to those requiring surgery and excluding other important medical complications such as deep venous thrombosis and pulmonary embolism.

DISCLOSURES:

The study received support from grants provided by the Cancer Research Foundation in Northern Sweden (Norrlands cancerforskningsfond), through a regional agreement between Umeå University and Vasterbotten County Council (ALF), and funding from the Swedish Breast Cancer Association. Per Karlsson, MD, PhD, disclosed receiving personal fees from AstraZeneca, Eli Lilly and Company, Novartis, Merck Sharp & Dohme, Roche, and Pfizer outside the submitted work. Karlsson also reported having a patent pending for intellectual property related to biomarkers for radiation sensitivity outside the submitted work. No other disclosures were reported by the authors of the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.