Association of Risk-Reducing Surgery in BRCA1 or BRCA2 Mutation Carriers with Cancer Risk and Mortality

By S. Domchek, T. Friebel, C. Singer, D. Evans, H. Lynch, C. Isaacs, J. Garber, S. Neuhausen, E. Matloff, R. Eeles and 13 more. Journal of the American Medical Association (JAMA), 2010

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Context Risk-reducing mastectomy (RRM) and salpingo-oophorectomy (RRSO) are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. Objectives To estimate risk and mortality reduction stratified by mutation and prior cancer status. Design A prospective multi-center cohort study was used to assess the relationship of RRM and RRSO on cancer outcomes. Setting Twenty-two clinical and research genetics centers in Europe and North America. Participants 2,482 women identified 1974-2008 and followed until the end of 2009 who tested positive for BRCA1 or BRCA2 mutations. Interventions 257 (10%) underwent RRM and 993 (40%) underwent RRSO. Main outcomes measures Breast and ovarian cancer risk; cancer-specific and overall mortality. Results No breast cancers were diagnosed in women with RRM compared to 7% of women without RRM. In women who underwent RRSO, 1.1% were subsequently diagnosed with ovarian cancer, 11.4% were subsequently diagnosed with breast cancer, and 3% subsequently died from any cause, compared with 5.8% ovarian cancer, 19.2% breast cancer, and 10% overall mortality in women who did not undergo RRSO. RRSO was associated with a lower risk of ovarian cancer in those with (Hazard Ratio (HR) 0.31, 95% CI 0.12-0.82) and without a prior breast cancer (HR 0.15, 0.04-0.63), and a lower risk of first breast cancer in both BRCA1 (HR 0.63, 0.41-0.96) and BRCA2 (HR 0.36, 0.16-0.82) mutation carriers. RRSO was associated with a reduction in all-cause (HR 0.40, 0.26-0.61), breast cancer-specific (HR 0.44, 0.26-0.76), and ovarian cancer-specific (HR 0.25, 0.08-0.75) mortality. Conclusions Among a cohort of women with BRCA1 and BRCA2 mutations, the use of RRM was associated with a lower risk of breast cancer, and RRSO was associated with a lower risk of ovarian cancer, first breast cancer, and overall, breast-, and ovarian-cancer specific mortality.

Subfields: Cancer Research, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/a33f21551a3d20040d720c2cc7d13d8b8542cf62

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Citations in the corpus

Lifetime Cancer Risks in Individuals with Germline PTEN Mutations (2012, background): “4–83 Pediatric subjects (%) <18 98 (27) Proband status (%) 295 (80) Mutation type (%) Missense 102 (28) Nonsense 109 (30) Small insertion 33 (9) Small deletion 47 (13) Small indel 5 (1) Splice junction 35 (10) Promoter 20 (5) Large deletion 17 (5) Lifetime Cancer Risks of PTEN Mutation Carriers”
Rethinking Ovarian Cancer: Recommendations for Improving Outcomes (2011, positive): “The identification of women who carry germline mutations in BRCA1 , BRCA2 , RAD51C and genes that encode other DNA repair proteins provides the most effective preventative strategy for high-grade serous ovarian cancers, as the removal of the ovaries and fallopian tubes can reduce the risk of dis”
American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. (2010, background): “Identifying inherited mutations in genes such as BRCA1, BRCA2, and the genes associated with Lynch syndrome allows for interventions that can significantly reduce the development of cancer and improve survival.(14,15) Testing for mutations in these genes has traditionally been directed by personal o”