In an international cohort study reported in The Lancet Oncology, Blondeaux et al evaluated whether both risk-reducing mastectomy and risk-reducing salpingo-oophorectomy were associated with improved survival among women aged 40 or younger who have invasive breast cancer with germline BRCA1/2 pathogenic variants.
Study Details
The study involved patients from the BRCA BCY Collaboration. The collaboration is a hospital-based, retrospective cohort study, conducted at 109 sites in five continents. It included women harboring germline BRCA1 or BRCA2 pathogenic variants and diagnosed with stage I to III invasive breast cancer at 40 years of age or younger between January 2000 and December 2020.
Key Findings
Among 5,290 women included in the analysis, 3,361 (63.5%) were BRCA1 pathogenic variant carriers and 1,891 (35.7%) were BRCA2 carriers. A total of 2,910 women (55.0%) underwent risk-reducing mastectomy, and 2,782 (52.6%) underwent risk-reducing salpingo-oophorectomy.
Median follow-up was 8.2 years (interquartile range = 4.7–12.8 years). Risk-reducing mastectomy was associated with significantly better overall survival compared with no risk-reducing mastectomy (adjusted hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.53–0.78), with a 20-year restricted mean overall survival time of 17.9 years (95% CI = 17.6–18.2 years) vs 16.6 years (95% CI = 16.4–16.9 years). The significant association was observed irrespective of specific BRCA gene, age at diagnosis, tumor subtype, tumor size, nodal status, chemotherapy use, and timing of BRCA testing.
Risk-reducing salpingo-oophorectomy was associated with significantly better overall survival compared with no risk-reducing salpingo-oophorectomy (adjusted HR = 0.58, 95% CI = 0.48–0.71), with a 20-year restricted mean overall survival time of 17.7 years (95% CI = 17.4–18.0 years) vs 16.7 years (95% CI = 16.4–17.0 years). The significant association was observed irrespective of age at diagnosis, tumor size, nodal status, chemotherapy use, and timing of BRCA testing. Among patients with risk-reducing salpingo-oophorectomy, significant interactions were observed according to specific BRCA gene (adjusted HRs = 0.44, 95% CI = 0.34–0.57 for BRCA1 carriers and 0.86, 95% CI = 0.64–1.15 for BRCA2 carriers; P = .0005 for interaction) and tumor subtype (adjusted HRs = 0.44, 95% CI = 0.33–0.58 for triple-negative; 0.80, 95% CI = 0.60–1.05 for luminal-like; and 0.50, 95% CI = 0.25–0.98 for HER2-positive; P = .0086 for interaction).
The investigators concluded: “In this global cohort of BRCA carriers with previous breast cancer diagnosis at a young age, [risk-reducing mastectomy] and [risk-reducing salpingo-oophorectomy] were both associated with a significant improvement in overall survival. These findings provide evidence for a tailored counseling of a unique and high-risk patient population on cancer risk management strategies.”
Matteo Lambertini, PhD, of the Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the Italian Association for Cancer Research. For full disclosures of all study authors, visit The Lancet Oncology.
