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

Neda Stjepanovic, Guillermo Villacampa, Kevin T. Nead, Sara Torres-Esquius, Guadalupe G. Melis, Katherine L. Nathanson, Alexandre Teule, Joan Brunet, Teresa R. y Cajal, Gemma Llort, Rodrigo Dienstmann, Montserrat Rue, Susan M. Domchek, Judith Balmaña

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalEuropean Journal of Cancer
Volume132
DOIs
StatePublished - Jun 2020

Keywords

  • BRCA1/2
  • Breast cancer risk
  • Multi-state model
  • Risk reduction methodology
  • Salpingo-oophorectomy
  • Systematic review

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Association of premenopausal risk-reducing salpingo-oophorectomy with breast cancer risk in BRCA1/2 mutation carriers: Maximising bias-reduction'. Together they form a unique fingerprint.

Cite this