Risk-reducing surgeries offer benefits for young BRCA mutation carriers

Risk-reducing surgeries offer benefits for young BRCA mutation carriers

In patients with BRCA germline mutations who were diagnosed with breast cancer at or before age 40 and underwent bilateral risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO), the rates of recurrence, secondary breast cancer, and breast cancer were low fewer ovarian malignancies and deaths than those who did not undergo these surgeries, according to findings presented at the San Antonio Breast Cancer Symposium (SABCS) April 10-13. December 2024.

“The benefits of RRM and RRSO have been demonstrated for BRCA mutation carriers without a history of cancer, but their effect for BRCA mutation carriers with a history of early-stage breast cancer is less clear,” said moderator Matteo Lambertini, MD, PhD, associate professor of medical oncology and consultant in medical oncology at the University of Genoa-IRCCS Policlinico San Martino Hospital in Genoa, Italy.

Both RRM and RRSO can impact a patient's quality of life, and RRSO also leads to infertility and early menopause, which can be particularly difficult for BRCA carriers with a history of breast cancer because they are not eligible for hormone replacement therapies that help relieve menopausal symptoms. Lambertini explained. “Given the unique characteristics and needs of this younger population and their high risk of secondary malignancies, it is important to understand how risk-reducing surgeries impact patient outcomes so that the risks and benefits of these procedures can be carefully considered,” he said.

To examine the association between RRM and/or RRSO and survival outcomes, Lambertini and colleagues conducted an analysis of the BRCA BCY Collaboration study, an international, multicenter, retrospective cohort study of patients with germline pathogenic or likely pathogenic BRCA variants diagnosed with stage 1–3 breast cancer aged 40 or younger between January 2000 and December 2020.

The analysis included 5,290 patients from 109 facilities on five continents. Of these patients, 3,888 underwent at least one risk-reducing surgery: 2,910 underwent RRM, 2,782 underwent RRSO, and 1,804 chose both RRM and RRSO. The remaining 1,402 patients did not undergo surgery.

The researchers found that performing RRM and/or RRSO was associated with improved outcomes after a median follow-up of 8.2 years.

Specifically, patients with an RRM had a 35% lower risk of death and a 42% lower risk of breast cancer recurrence or a second primary malignancy. The improved outcomes were observed regardless of whether the germline BRCA mutation was present in the BRCA1 or BRCA2 gene.

Patients who underwent RRSO had a 42% lower risk of death and a 32% lower risk of breast cancer recurrence or a second primary malignancy. The benefit of RRSO on overall survival varied depending on the mutated BRCA gene, with the survival benefit being greater for patients with germline mutations in BRCA1 than in BRCA2 (56% and 15% lower risk of death, respectively). When examined by breast cancer subtype, researchers found that RRSO had the greatest survival benefit for patients with triple-negative breast cancer (56% lower risk of death), followed by hormone receptor-positive breast cancer (20% lower risk of death). .

Overall survival was similar between patients who underwent both operations and those who underwent only one operation.

This global study provides the first evidence that risk-reducing surgery improves survival outcomes in young BRCA mutation carriers with a history of early-stage breast cancer. We believe our findings are critical to improving counseling for BRCA mutation carriers with early-stage breast cancer on cancer risk management strategies.”

Matteo Lambertini, MD, PhD, Associate Professor of Medical Oncology and Consultant in Medical Oncology, University of Genoa-IRCCS Policlinico San Martino Hospital

Limitations of the study include its retrospective design and the inclusion of patients from different health systems with different resources and guidelines. In addition, the analysis includes patients treated over a 20-year period during which recommendations for germline BRCA testing and risk-reducing surgery have evolved. In addition, the results could have been biased if patients with a better prognosis were more likely to be recommended risk-reducing surgeries.

The study was supported by the Italian Association for Cancer Research (AIRC) and the European Society for Medical Oncology (ESMO). Lambertini reports consulting roles for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead, MSD, Exact Sciences, Pierre Fabre and Menarini; Speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini and AstraZeneca; travel grants from Gilead, Daiichi Sankyo and Roche; and research funding for his institution from Gilead.

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