Abstract P5-09-04: Impact of premenopausal RRSO on breast cancer risk in BRCA1/2 mutation carriers: Maximizing bias-reduction
Authors: Stjepanovic N , Villacampa G , Nead K , Torres S , Gomez L , Nathanson KL , Teule A , Brunet J , Ramon y Cajal T , Llort G , Dienstmann R , Rue M , Domchek S , Balmana J 
Published: May 2019

Abstract
Background:
To prevent ovarian cancer in BRCA1/2 mutation carriers, risk reducing salpingo-oophorectomy (RRSO) is recommended around age 40. In women with no prior history of cancer, there are conflicting data regarding the impact of RRSO on breast cancer risk. Our aim was to explore the association between premenopausal RRSO and BC risk by using a methodology that maximally reduced potential biases.
Methods:
Prospective multicenter cohort study of BRCA1/2 carriers who underwent genetic testing under age 51, had no history of bilateral salpingo-oophorectomy, mastectomy or cancer prior to genetic testing and during the first six months of surveillance (to avoid cancer-induced testing bias and prevalent cancer bias). Observation period started six months after genetic testing (to avoid event-free time bias), and ended at BC or other cancer diagnosis except for non-melanoma skin cancer and cervical cancer in situ, risk reducing mastectomy (RRM), last follow-up or death. We calculated person-years of observation (PYO) starting at age 30 and RRSO was only accounted for when performed before age 51 (considered premenopausal). Cox proportional hazards models with RRSO as a time-dependent covariate (to avoid immortal person time bias) were used to calculate the BC risk reduction. Sensitivity analysis, censoring at age 51, was performed to calculate the impact of RRSO on the premenopausal BC.
Results:
We included 853 (444 BRCA1 and 409 BRCA2) women. Median age was 36.2 (30-50.9) years, 337 (39.5%) women underwent RRSO prior to age 51 with a median age at RRSO of 42.8 (30.5-50.9) and 240 (28.1%) women performed RRM at a median age of 40.7 (30-61.7) years.
After a mean follow-up period of 4.3 years, 96 women (11.3%) were diagnosed with BC (54 BRCA1 and 42 BRCA2). Overall, women who underwent RRSO had a significant reduction in BC risk with hazard ratio (HR) of 0.57 (95% CI= 0.32 to 1; p=0.05); in BRCA1 carriers we found HR of 0.45 (95% CI= 0.22 to 0.92; p=0.03), while BRCA2 carriers had HR of 0.77 (95% CI= 0.35 to 1.67; p=0.51).
When follow-up was censored at age 51, the HR estimates remained similar with overall HR of 0.54 (95% CI= 0.29 to 1; p=0.05); BRCA1 carriers had HR of 0.35 (95% CI= 0.15 to 0.82; p=0.02), while BRCA2 carriers had HR of 0.88 (95% CI= 0.39 to 1.96; p=0.75).
Conclusions:
This robust bias-reducing analysis in a large prospective cohort supports a role of premenopausal RRSO for BC risk reduction in BRCA1 carriers. A longer follow-up may be needed to estimate the potential benefit of the intervention in BRCA2 carriers.
Citation Format: Stjepanovic N, Villacampa G, Nead K, Torres S, Gomez L, Nathanson KL, Teule A, Brunet J, Ramon y Cajal T, Llort G, Dienstmann R, Rue M, Domchek S, Balmana J. Impact of premenopausal RRSO on breast cancer risk in BRCA1/2 mutation carriers: Maximizing bias-reduction [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-09-04.