Dutch Analysis Questions Breast Cancer Protective Effect of Salpingo-Oophorectomy in Healthy BRCA1/2 Mutation Carriers

Key Points

  • Previous studies have reported a marked breast cancer risk reduction after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers.
  • The current analysis using risk-reducing salpingo-oophorectomy as a time-dependent variable did not show a risk reduction.

In a Dutch study reported in the Journal of the National Cancer Institute, Heemskerk-Gerritsen et al in the Hereditary Breast and Ovarian Cancer in the Netherlands (HEBON) study group found no apparent reduction in the risk for breast cancer with salpingo-oophorectomy in healthy BRCA1/2 mutation carriers. Their analysis used risk-reducing salpingo-oophorectomy as a time-dependent variable.

Study Details

The analysis involved BRCA1/2 mutation carriers from the ongoing nationwide HEBON study. Assessment of risk was first carried out using analytic methods previously used in four major studies of breast cancer risk after risk-reducing salpingo-oophorectomy, with Cox proportional hazard models used to calculate hazard ratios (HRs) and conditional logistic regression used to calculate odds ratios (ORs). The data were reanalyzed in a revised design aimed at further minimizing bias by using an extended Cox model with risk-reducing salpingo-oophorectomy as a time-dependent variable to calculate HRs. This approach differed from methods used in other studies by requiring absence of a history of cancer at the date of DNA diagnosis and including person-time preceding risk-reducing salpingo-oophorectomy.

Difference in Risk Estimates

Use of the analytic methods of the four trials for data from 551 to 934 BRCA1/2 mutation carriers in the HEBON cohort with a median follow-up of 2.7 to 4.6 years yielded an OR of 0.61 (95% confidence interval [CI] = 0.35–1.08) and HRs of 0.36 (95% CI = 0.25–0.53), 0.62 (95% CI = 0.39–0.99), and 0.49 (95% CI = 0.33–0.71) for risk of breast cancer in patients undergoing risk-reducing salpingo-oophorectomy. In the revised analysis in 822 BRCA1/2 mutation carriers with a median follow-up of 3.2 years, the HR for breast cancer after risk-reducing salpingo-oophorectomy was 1.09 (95% CI = 0.67–1.77).

The investigators concluded: “In previous studies, [breast cancer] risk reduction after [risk-reducing salpingo-oophorectomy] in BRCA1/2 mutation carriers may have been overestimated because of bias. Using a design that maximally eliminated bias, we found no evidence for a protective effect.”

M. J. Hooning, MD, PhD, of Erasmus MC Cancer Institute, is the corresponding author of the Journal of the National Cancer Institute article.

The study was supported by the Dutch Cancer Society, Netherlands Organization of Scientific Research, Pink Ribbon, and Biobanking and Biomolecular Resources Research Infrastructure Grants.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.