Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction

Eur J Cancer. 2020 Jun:132:53-60. doi: 10.1016/j.ejca.2020.03.009. Epub 2020 Apr 20.

Abstract

Background: Whether risk-reducing salpingo-oophorectomy (RRSO) in BRCA1/2 carriers reduces the breast cancer (BC) risk is conflicting, potentially due to methodological issues of prior analysis. We analysed the association between premenopausal RRSO and BC risk in BRCA1/2 carriers after adjusting for potential biases.

Methods: We analysed data from 444 BRCA1 and 409 BRCA2 carriers under age 51 with no cancer prior to genetic testing or during first 6 months of surveillance (to avoid cancer-induced testing bias and prevalent-cancer bias). Observation started 6 months after genetic testing (to avoid event-free time bias), until BC diagnosis, risk-reducing mastectomy (RRM) or death. A multistate model with four states (non-RRSO, RRSO, RRM and BC) and five transitions was fitted to characterise outcomes and to calculate the BC risk reduction after premenopausal RRSO (before age 51). A systematic review was performed to assess the association between premenopausal RRSO and BC.

Results: During a mean follow-up of 4.3 years, 96 women (11.3%) developed BC (54 BRCA1, 42 BRCA2). The risk of BC after premenopausal RRSO decreased significantly in BRCA1 carriers (hazard ratio (HR) = 0.45 [95% confidence interval (CI):0.22-0.92]), but was not conclusive in BRCA2 carriers (HR = 0.77 [95%CI:0.35-1.67]). The systematic review suggested that premenopausal RRSO is associated with a decrease of BC risk in both BRCA1 and BRCA2 carriers.

Conclusions: Premenopausal RRSO was associated with BC risk reduction in BRCA1 carriers, which can help guide cancer risk-reducing strategies in this population. Longer follow-up and larger sample size may be needed to estimate the potential benefit in BRCA2 carriers.

Keywords: BRCA1/2; Breast cancer risk; Multi-state model; Risk reduction methodology; Salpingo-oophorectomy; Systematic review.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery*
  • Female
  • Follow-Up Studies
  • Genetic Testing
  • Germ-Line Mutation*
  • Humans
  • Middle Aged
  • Premenopause*
  • Prognosis
  • Prospective Studies
  • Retrospective Studies
  • Risk Reduction Behavior*
  • Salpingo-oophorectomy / methods*
  • Young Adult

Substances

  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 Protein
  • BRCA2 protein, human