Barr, Lester

Clayton, Richard D

Crosbie, Emma

Edmondson, Richard

Evans, D Gareth

Gandhi, Ashu

Harkness, Elaine

Harvey, James

Highton, Lindsey

Holland, Catherine

Howell, Sacha

Howell, Tony

Lalloo, Fiona

Marcinkute, Ruta

Murphy, John

Wisely, Julie

Woodward, Emma

Background: Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers.Methods: Women were prospectively followed-up from positive genetic test (GT) result to censor date. Chi-squared testing compared categorical variables; Cox regression model estimated hazard ratios and 95%CI for breast/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.Results: In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01-24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO–10.0 months. Annual breast cancer incidence in the study population was 1.28%. Relative breast cancer risk reduction (RRM vs non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO vs non-RRSO) was 100%. Conclusion: Over a 24-year period we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC. <br/

The University of Manchester - Institutional Repository

English

Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers

Uptake and efficacy of bilateral risk reducing surgery in unaffected female BRCA1 and BRCA2 carriers

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The University of Manchester - Institutional Repository