Association of Premenopausal Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in BRCA1/2 Mutation Carriers: Maximising Bias-Reduction - PubMed

Association of Premenopausal Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in BRCA1/2 Mutation Carriers: Maximising Bias-Reduction - PubMed

Association of Premenopausal Risk-Reducing Salpingo-Oophorectomy With Breast Cancer Risk in BRCA1/2 Mutation Carriers: Maximising Bias-Reduction

Neda Stjepanovic 1, Guillermo Villacampa 2, Kevin T Nead 3, Sara Torres-Esquius 4, Guadalupe G Melis 5, Katherine L Nathanson 6, Alexandre Teule 7, Joan Brunet 8, Teresa R Y Cajal 9, Gemma Llort 10, Rodrigo Dienstmann 11, Montserrat Rue 12, Susan M Domchek 13, Judith Balmaña 14

Affiliations 

• PMID: 32325420
 
• DOI: 10.1016/j.ejca.2020.03.009

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.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Conflict of interest statement

Conflict of interest statement The authors declare no conflicts of interest.

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