Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
Survival Outcomes With or Without Risk-Reducing Mastectomy in BRCA1 and BRCA2 Pathogenic Variant Carriers.
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Gandhi Ashu, Howell Sacha J, Harkness Elaine F, Woodward Emma, Lalloo Fiona, Forde Claire, Harvey James, Highton Lyndsey, Flaum Nicola, Evans D Gareth
Аннотация
PURPOSE: Many women carrying pathogenic variants (pvs) of BRCA1 and BRCA2 genes (pvBRCA1/2) elect to undergo bilateral risk-reducing mastectomy (BRRM) in the belief that it will improve their overall survival (OS). Although many are satisfied with their decision to undergo BRRM a significant minority exhibit regret. We compared long-term oncology outcomes in women with pvBRCA1/2 choosing BRRM with those choosing a program of imaging surveillance.
METHODS: All participants were attendees at a regional family history/genetics service and had undergone genetic testing for pvBRCA1/2. Carriers of pvBRCA1/2 elected either to undergo BRRM or imaging surveillance as directed by UK national guidance. A prospective cohort design examined OS, breast cancer-specific death, and breast cancer incidence between the study groups.
RESULTS: A total of 460 women elected to undergo BRRM, while 745 chose surveillance (median age, 37.2 years and 38.5 years, respectively; P = .06). Follow-up totaled 4,652 woman-years after BRRM. Overall annual incidence rate of breast cancer was 2.4%, falling to 0.15% after BRRM, a 94% reduction compared with surveillance alone (log-rank chi-square = 86.1; P < .001). There were nine occult cancers diagnosed at BRRM (2%). Breast cancer-specific deaths were similar in the BRRM and surveillance groups (two and four deaths, respectively; P = .36; 4,634 and 5,419 woman-years of follow-up, respectively). Proportionately, deaths from breast cancer were similar to deaths from ovarian cancer in both treatment groups.
CONCLUSION: For women electing imaging surveillance over risk-reducing surgery, our results may offer reassurance that their breast cancer-specific survival and OS are unlikely to be compromised. However, breast cancer incidence rates are significantly reduced after BRRM compared with imaging surveillance, which may be important information for women with pvBRCA1/2 considering BRRM.
METHODS: All participants were attendees at a regional family history/genetics service and had undergone genetic testing for pvBRCA1/2. Carriers of pvBRCA1/2 elected either to undergo BRRM or imaging surveillance as directed by UK national guidance. A prospective cohort design examined OS, breast cancer-specific death, and breast cancer incidence between the study groups.
RESULTS: A total of 460 women elected to undergo BRRM, while 745 chose surveillance (median age, 37.2 years and 38.5 years, respectively; P = .06). Follow-up totaled 4,652 woman-years after BRRM. Overall annual incidence rate of breast cancer was 2.4%, falling to 0.15% after BRRM, a 94% reduction compared with surveillance alone (log-rank chi-square = 86.1; P < .001). There were nine occult cancers diagnosed at BRRM (2%). Breast cancer-specific deaths were similar in the BRRM and surveillance groups (two and four deaths, respectively; P = .36; 4,634 and 5,419 woman-years of follow-up, respectively). Proportionately, deaths from breast cancer were similar to deaths from ovarian cancer in both treatment groups.
CONCLUSION: For women electing imaging surveillance over risk-reducing surgery, our results may offer reassurance that their breast cancer-specific survival and OS are unlikely to be compromised. However, breast cancer incidence rates are significantly reduced after BRRM compared with imaging surveillance, which may be important information for women with pvBRCA1/2 considering BRRM.