Risk-reducing surgery increases survival in BRCA1/2 mutation carriers unaffected at time of family referral
ABSTRACT The aim of this study was to establish if risk-reducing surgery (RRS) increases survival among BRCA1/2 carriers without breast/ovarian cancer at the time of family referral. Female BRCA1/2 carriers were identified from the Manchester Genetic Medicine Database. Those patients alive and unaffected at the date of first family ascertainment were included in this study. Female first-degree relatives (FDRs) without predictive genetic testing who otherwise met eligibility criteria were also included. The effect of breast and ovarian RRS on survival was analysed. The survival experiences of RRS and non-RRS patients, stratified by BRCA status, were examined with Kaplan-Meier curves and contrasted using log-rank tests and Cox models. 691 female BRCA1/2 mutation carriers without breast or ovarian cancer at time of family ascertainment were identified; 346 BRCA1 and 345 BRCA2. 105 BRCA1 carriers and 122 BRCA2 carriers developed breast cancer during follow-up. The hazard of death was statistically significantly lower (P < 0.001) following RRS versus no RRS. 10-year survival for women having RRS was 98.9 % (92.4-99.8 %) among BRCA1 and 98.0 % (92.2-99.5 %) among BRCA2 carriers. This survival benefit with RRS remained significant after FDRs were added. Women who had any form of RRS had increased survival compared to those who did not have RRS; a further increase in survival was seen among women who had both types of surgery. However, formal evidence for a survival advantage from bilateral mastectomy alone requires further research.
- SourceAvailable from: Dafydd Gareth EvansBMJ: British medical journal 04/2014; 348:g2756.. DOI:10.1136/bmj.g2756
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ABSTRACT: This article reviews the evidence that underpins breast cancer screening and prevention strategies for women at high risk of the disease, with a particular focus on evidence published in the last 18 months. The review is timely because the US National Comprehensive Cancer Network, the UK National Institute for Health and Care Excellence and the American Society of Clinical Oncology have recently updated relevant guidelines that inform practice. In the recently published literature, there have been several important findings. A meta-analysis of randomized trials of selective oestrogen receptor modulators (SERMs), along with the first results from the International Breast Cancer Intervention Study II trial, further support the use of SERMs and aromatase inhibitors in the primary prevention of breast cancer. A large observational study has provided evidence that the SERM tamoxifen may be efficacious for breast cancer prevention in women who carry mutations in the breast cancer predisposition genes, BRCA1 and BRCA2. Several observational studies have suggested that contralateral risk-reducing mastectomy, following a diagnosis of breast cancer, may reduce mortality. Evidence regarding the optimal management of women at high risk of breast cancer continues to evolve and needs to be rapidly implemented into clinical practice.Current Opinion in Obstetrics and Gynecology 12/2014; 27(1). DOI:10.1097/GCO.0000000000000140