Medical Research: What is the background for this study? What are the main findings?
Dr. Heemskerk-Gerritsen: Women with a BRCA1 or BRCA2 mutation have substantially higher risks of developing both primary and contralateral breast cancer (BC) and ovarian cancer than women from the general population. Options to reduce these increased cancer risks include risk-reducing mastectomy (RRM) and/or risk-reducing salpingo-oophorectomy (RRSO). The latter intervention obviously reduces the risk of developing ovarian cancer, but has been reported also to reduce the risk of developing a subsequent breast cancer with approximately 50%. However, studies on the efficacy of risk-reducing surgery in BRCA1/2 mutation carriers are confined to observational studies, thus challenging several methodological issues. Consequently, previous studies on breast cancer risk-reduction after RRSO may have been influenced by bias associated with selection of study subjects, bias associated with start of follow-up, or by confounding, and breast cancer risk-reduction may have been overestimated.
In the current study, we revisited the association between risk-reducing salpingo-oophorectomy and breast cancer risk in BRCA1/2 mutation carriers, focusing on the impact of different analytical methods and potential types of bias.
First, we replicated the analyses of four previously performed studies, to examine if our Dutch cohort was comparable with the cohorts used in the previous studies. We replicated the approximately 50% breast cancer risk reduction after RRSO in the Dutch cohort.
Second, we estimated the effect of RRSO on breast cancer risk in the Dutch cohort using a revised analytical approach for observational studies in BRCA1/2 mutation carriers in order to minimize bias as much as possible. Using this method of analysis, we found no evidence of first BC risk-reduction after RRSO in BRCA1/2 mutation carriers.
Medical Research: What should clinicians and patients take away from your report?
Dr. Heemskerk-Gerritsen: From the results, we concluded that in previous studies, breast cancer risk reduction after RRSO in BRCA1/2 mutation carriers may have been overestimated because of bias. We suggest that counselors, clinicians, and researchers should consider the potential impact of bias in previous and future observational studies on this topic. For the present, we advise caution in the message regarding breast cancer risk reduction after RRSO, at least for BRCA1 mutation carriers.
Medical Research: What recommendations do you have for future research as a result of this study?
Dr. Heemskerk-Gerritsen: We are very interested in the risk estimates in the previous study cohorts when using our proposed design and analytical method, and in validation of our findings. Additionally, further research with longer follow-up and larger numbers of especially BRCA2 mutation carriers is warranted to explore differential effects on BC risks after RRSO for BRCA1 and BRCA2 mutation carriers.
Breast Cancer Risk After Salpingo-Oophorectomy in Healthy BRCA1/2 Mutation Carriers: Revisiting the Evidence for Risk Reduction
MedicalResearch.com Interview with: Bernadette A.M. Heemskerk-Gerritsen, Ph.D. (2015). Breast Cancer Risk Reduction of Prophylactic Salpingo-Oophorectomy May Be Overestimated For Some BRCA1 Carriers MedicalResearch.com