RT Journal Article
SR Electronic
T1 Uptake and efficacy of bilateral risk reducing surgery in unaffected female <em>BRCA1</em> and <em>BRCA2</em> carriers
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 133
OP 140
DO 10.1136/jmedgenet-2020-107356
VO 59
IS 2
A1 Ruta Marcinkute
A1 Emma Roisin Woodward
A1 Ashu Gandhi
A1 Sacha Howell
A1 Emma J Crosbie
A1 Julie Wissely
A1 James Harvey
A1 Lindsay Highton
A1 John Murphy
A1 Cathrine Holland
A1 Richard Edmondson
A1 Richard Clayton
A1 Lester Barr
A1 Elaine F Harkness
A1 Anthony Howell
A1 Fiona Lalloo
A1 D Gareth Evans
YR 2022
UL http://jmg.bmj.com/content/59/2/133.abstract
AB Background Women testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) 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. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/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 BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus 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.All data relevant to the study are included in the article or uploaded as supplementary information.