Bilateral oophorectomy is recommended for women with BRCA1 or BRCA2 sequence variations to reduce their risk of developing ovarian or fallopian tube cancer. Building on previous research, Joanne Kotsopoulos, PhD, and colleagues conducted a multinational study of women with a pathogenic or likely pathogenic germline variant in the BRCA1 or BRCA2 gene to determine whether there is an association between bilateral oophorectomy and all-cause mortality in women.
In this largest prospective cohort study of its kind, 4,332 women were observed for up to 24 years for incident cancers and death from all causes. The study results suggest that oophorectomy is associated with a significant reduction in all-cause mortality in this population. Among 901 incident cancers diagnosed, more than half were breast cancer; 2,932 women underwent a preventive oophorectomy, including 66% of those with BRCA1 sequence variations and 72% of those with BRCA2 sequence variations. The rate of death was lower among these women (3.8%) vs those who did not have an oophorectomy (8.3%). The age-adjusted hazard ratio for all-cause mortality associated with oophorectomy was 0.32, with the lowest hazard ratio among women with BRCA1 sequence variations vs BRCA2. This risk reduction was similar regardless of age at surgery.
The recommended age for oophorectomy is 40 years for those with BRCA1 and 45 years for those with BRCA2 sequence variations. According to this study, only about one-third of women had an oophorectomy by the recommended age. Based on age-specific rates and consistent with earlier reports, the estimated all-cause cumulative mortality rate for women with a BRCA1 sequence variation was 25% for those who had oophorectomy at age 35 vs 62% for those who never had an oophorectomy. For women with BRCA2, all-cause cumulative mortality was 14% in those who had an oophorectomy at age 35 vs 28% for those who retained their ovaries. These findings contrast with those for women in the general population, where premenopausal oophorectomy in women with average cancer risk is associated with an increased risk of death from cardiovascular disease and a decline in quality of life.
High level
The results of this study reinforce the current guidelines for oophorectomy between ages 35 and 40 for women with BRCA1 sequence variations and before age 45 for those with BRCA2 sequence variations. Clinical pathways and protocols should consider the association between bilateral oophorectomy and all-cause mortality and incorporate this guidance to help reduce mortality in women with a BRCA sequence variation.
Ground level
This large cohort study of bilateral oophorectomy and all-cause mortality in women shows that only about one-third of those with BRCA1 and BRCA2 sequence variations have an oophorectomy by the recommended age. Clinicians can help increase these numbers by using the results of this study to educate at-risk patients on the risks of waiting or not having an oophorectomy, while taking care to be sensitive to the individual patient’s needs and concerns.