Patients with early-onset breast cancer (aged 40 or younger at diagnosis) who have BRCA1 and/or BRCA2 pathogenic or likely pathogenic variants had improved overall survival by undergoing risk-reducing surgeries, including bilateral mastectomy and/or salpingo-oophorectomy, according to data presented at the 2024 San Antonio Breast Cancer Symposium.1
For those who had risk-reducing mastectomy, at 5 years, they had a 35% reduced risk of dying, and both disease-free survival and breast cancer–free interval were significantly improved. These outcomes were observed in both BRCA1 and BRCA2 carriers. Those treated with salpingo-oophorectomy had a 42% reduced risk of dying, and disease-free survival and breast cancer–free survival were improved compared with those who did not.
Matteo Lambertini, MD, PhD
“This global study provides evidence that risk-reducing surgeries improve survival outcomes among young BRCA carriers with a history of early-onset breast cancer,” said lead investigator Matteo Lambertini, MD, PhD, Associate Professor of Medical Oncology and a consultant in medical oncology at the University of Genova–IRCCS Policlinico San Martino Hospital, Genoa, Italy. “Considering the unique traits and needs of this younger population, and their high risk for secondary malignancies, it is critical to understand how risk-reducing surgeries affect patient outcomes, so the risks and benefits of these procedures can be carefully weighed,” he added.
“We hope these findings may help to improve the counseling on cancer-risk management strategies for BRCA carriers with a young onset of breast cancer at age 40 or younger at diagnosis,” Dr. Lambertini told listeners at a press briefing prior to the formal presentation. “However, these findings should not be used to counsel healthy BRCA carriers nor BRCA carriers diagnosed with breast cancer at an older age,” he emphasized.
The benefits of risk-reducing strategies (including risk-reducing surgeries) are known for BRCA carriers without a history of cancer, but their impact on younger BRCA carriers with a diagnosis of breast cancer is less clear, according to Dr. Lambertini. The present study was conducted to determine the impact of two types of risk-reducing surgeries on BRCA carriers with an early onset of breast cancer (at age 40 or younger at diagnosis).
Two Different Analyses
The recent findings come from the BRCA BCY Collaboration, an international, multicenter, retrospective cohort study of 5,290 patients from 109 institutions across 5 continents. Patients had germline BRCA1 and/or BRCA2 pathogenic variants, with a diagnosis of stage I–III breast cancer at age 40 or younger.
Median follow-up was 8.2 years. Median age at diagnosis was 35. Approximately two-thirds (63.5%) were BRCA1 carriers, 35.7% were BRCA2 carriers, and 0.6% were both BRCA1 and BRCA2 carriers. About half the population had node-negative disease; 35.9% had luminal-like breast cancer, and 49.1% had triple-negative breast cancer. Most patients (91.8%) received chemotherapy. Tumor size was ≤ 2 cm in 36.5%, between 2 and 5 cm in 45.6%, and > 5 cm in 13.6%.
The risk-reducing mastectomy analysis included 2,910 patients (55%) who underwent the surgery with a median time from diagnosis of land 2,380 who opted not to have the surgery. The primary endpoint was overall survival; disease-free survival and breast cancer–free interval were secondary endpoints. To explore the association between risk-reducing surgeries and survival outcomes, Cox models were used with risk-reducing mastectomy and risk-reducing salpingo-oophorectomy included as time-dependent covariates. Overall survival models were adjusted for the development of distant recurrences or second primary malignancies as time-dependent covariates.
Key Results
During a median follow-up of 5.1 years, patients who underwent risk-reducing mastectomy had a 35% lower risk of death as well as a significant 42% improvement in both disease-free survival and a 45% improvement in breast cancer–free interval. The survival benefits were observed in both BRCA1 and BRCA2 carriers.
The risk-reducing salpingo-oophorectomy analysis included 2,782 patients who underwent this surgery a median of 3 years from diagnosis of breast cancer and 2,508 who did not. At a median follow up of 4.9 years, risk-reducing salpingo-oophorectomy was associated with a 42% lower risk for death, as well as a 32% improvement in both disease-free survival and a 35% improvement in breast cancer–free survival. An interaction was observed between risk-reducing salpingo-oophorectomy and specific BRCA pathogenic variants as well as breast cancer subtype.
Overall survival results were similar in patients who underwent either or both surgeries.
“Specifically, the benefit of risk-reducing salpingo-oophorectomy was greater for patients with BRCA1 pathogenic variants and for those with triple-negative breast cancer, as compared with those with BRCA2 pathogenic variants or luminal disease,” Dr. Lambertini told listeners.
Kate Lathrop, MD
Additional Comment
Press briefing moderator Kate Lathrop, MD, of The University of Texas Health Science Center at San Antonio, noted that this study provides valuable information for counseling younger patients. “Having data sets like these helps us give patients potentially our best estimate of the amount of reduction of risk you could have by having the surgery now,” she said. “This is important for young women who may want to balance wanting to have more children and avoiding a recurrence.”
DISCLOSURE: The study was supported by the Italian Association for Cancer Research and the European Society for Medical Oncology. Dr. Lambertini has served in an advisor role for Roche, Lilly, Novartis, AstraZeneca, Pfizer, Seagen, Gilead Sciences, MSD, Exact Sciences, Pierre Fabre, and Menarini; has received speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Takeda, Menarini, and AstraZeneca; has received travel grants from Gilead Sciences, Daiichi Sankyo, and Roche; and has received institutional research funding from Gilead Sciences. Dr. Lathrop has served as a consultant to TeraSera Pharmaceuticals.
REFERENCE
- Lambertini M, Sonnenblick A, Agostinetto E, et al: Association between risk-reducing surgeries and survival in young BRCA carriers with breast cancer: Results from an international cohort study. 2024 San Antonio Breast Cancer Symposium. Abstract GS1-08. Presented December 11, 2024.
