Risk-reducing surgeries extend survival among young BRCA carriers with breast cancer history
Key takeaways:
- Risk-reducing mastectomy and risk-reducing salpingo-oophorectomy conferred a survival benefit.
- The findings may improve counseling of this patient population.
SAN ANTONIO — Risk-reducing surgery appeared linked with improved outcomes among BRCA mutation carriers diagnosed with early breast cancer, according to study results presented at San Antonio Breast Cancer Symposium.
Those who underwent bilateral risk-reducing mastectomy and/or risk-reducing salpingo-oophorectomy exhibited reduced risk for recurrence, lower incidence of secondary breast and/or ovarian cancers, and reduced mortality risk.
“This global study provides the first evidence that risk-reducing surgeries improve survival outcomes among young BRCA mutation carriers with a prior history of early-onset breast cancer,” Matteo Lambertini, MD, PhD, associate professor of medical oncology and consultant in medical oncology at University of Genova-IRCCS Policlinico San Martino Hospital in Italy, said in a press release. “We believe that our findings are critical for improving the counseling of BRCA mutation carriers with early-onset breast cancer on cancer-risk management strategies.”
Cancer risk-management strategies are recommended for healthy individuals who carry germline pathogenic or likely pathogenic variants in BRCA1 and BRCA2 genes.
Prior research showed risk-reducing salpingo-oophorectomy improves OS. Bilateral risk-reducing mastectomy reduces breast cancer risk but no OS benefit has been confirmed, according to study background.
However, other factors must be considered when deciding if these strategies are appropriate for people with prior breast cancer history, Lambertini said.
The risk for relapse of the primary breast cancer must be balanced with risk for second primary malignancy. In addition, both surgeries can have negative effects on quality of life.
Risk-reducing salpingo-oophorectomy also can lead to infertility and early menopause — a particular challenge for BRCA carriers with breast cancer history because they are ineligible for hormone replacement therapies.
“The benefits of risk-reducing salpingo-oophorectomy and risk-reducing mastectomy have been shown for BRCA mutation carriers without a prior history of cancer, but their impact for BRCA mutation carriers with a history of early-onset breast cancer is less clear,” Lambertini said in a press release. “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 that the risks and benefits of these procedures can be carefully weighed.”
Lambertini and colleagues conducted the BRCA BCY Collaboration — an international, multicenter retrospective cohort study — to evaluate the association between these risk-reducing strategies and survival in a large global cohort of BRCA carriers who had been diagnosed with breast cancer prior to age 40 years.
The analysis included data from 5,290 patients (median age at diagnosis, 35; interquartile range, 31-38)treated at 109 institutions on five continents.
All patients had germline pathogenic or likely pathogenic BRCA variants, and all had been diagnosed with stage I to stage III breast cancer at age 40 years or younger between January 2000 and December 2020.
Those with stage IV de novo breast cancer and history of ovarian cancer were excluded, as were healthy BRCA carriers or those with BRCA variants of unknown significance.
Researchers strived to account for potential lead time bias by conducting two sensitivity analyses. One included only patients tested for BRCA status prior to or at breast cancer diagnosis. They also performed a survival model through which observation times were left truncated at the time of BRCA testing.
Investigators also conducted a 3-year landmark analysis that included only patients alive and observed 3 years after breast cancer diagnosis to account for potential guarantee-time bias.
About three-quarters (73.4%; n = 3,888) of the cohort underwent at least one risk-reducing surgery (risk-reducing mastectomy, n = 2,910; risk-reducing salpingo-oophorectomy, n = 2,782; both, n = 1,804).
Median follow-up was 8.2 years (interquartile range, 4.7-12.8).
Results showed patients who underwent either or both of the risk-reducing surgeries experienced better outcomes.
Those who underwent risk-reducing mastectomy exhibited a 35% reduced risk for death (adjusted HR = 0.65; 95% CI, 0.53-0.78). They also achieved longer DFS (adjusted HR = 0.58; 95% CI, 0.52-0.62) and breast cancer-free interval (adjusted HR = 0.55; 95% CI, 0.48-0.62).
The benefits persisted regardless of whether the germline mutations was present in the BRCA1 gene or BRCA2 gene.
Those who underwent risk-reducing salpingo-oophorectomy exhibited a 42% reduced risk for death (adjusted HR = 0.58; 95% CI, 0.48-0.71). They also achieved longer DFS (adjusted HR = 0.68; 95% CI, 0.61-0.77) and breast cancer-free interval (adjusted HR = 0.65; 95% CI, 0.57-0.74).
The survival benefit with risk-reducing salpingo-oophorectomy appeared greater among those who had BRCA1 germline mutations (56% reduction in risk for death) than BRCA2 germline mutations (15% reduction in risk for death).
The survival benefit also varied by breast cancer subtype. Those who had been diagnosed with triple-negative breast cancer exhibited a 56% reduction in risk for death, whereas those diagnosed with hormone receptor-positive breast cancer exhibited a 20% reduction in risk for death.
Researchers observed no difference in survival between individuals who underwent both risk-reducing strategies vs. those who underwent one.
Investigators acknowledged study limitations, including its retrospective design and the fact the analysis included patients from health care systems with different guidelines and resources.
The study also included patients treated over 2 decades. Researchers noted recommendations for BRCA testing and risk-reducing approaches have evolved during that time.
Nonetheless, the findings can help guide counseling of BRCA carriers diagnosed with young-onset breast cancer, researchers concluded.
“For risk-reducing salpingo-oophorectomy, the indication — irrespective of prior breast cancer diagnosis — is quite clear from the guidelines: BRCA1 carriers should have the it between the ages of 35 to 40 years, and BRCA2 carriers should have it between the ages of 40 to 45 years,” Lambertini told Healio. “In this special population, I would make more of a push with my patients to encourage them to have this surgery at this specific age.
“For risk-reducing mastectomy, the case is more complicated,” Lambertini added. “It’s a shared decision with the patient about the risks and potential benefit. However, in this special population — based on these data — I once again would be more willing to push toward the need to undergo risk-reducing bilateral mastectomy.”
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Lambertini M, et al. Abstract GS1-08. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.
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