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TOPLINE:

Bilateral oophorectomy significantly reduces the risk for early death from any cause in women with a pathogenic variant in the BRCA1/2 genes, new data confirm.

METHODOLOGY:

• Women who carry pathogenic variants in BRCA1/2 are at an increased risk for breast and ovarian cancer and are encouraged to undergo risk-reducing bilateral salpingo-oophorectomy. However, the association of oophorectomy with all-cause mortality has yet to be clearly defined.
• In a longitudinal study of women with a BRCA1/2 sequence variation but no prior cancer diagnosis, researchers evaluated the association between bilateral oophorectomy and all-cause mortality and calculated age-specific annual mortality rates for women with and without intact ovaries.
• The women were followed up from age 35 to 75 years for incident cancer and death. Oophorectomy status was updated every 2 years during the follow-up.

TAKEAWAY:

• Among a total of 4332 BRCA1/2 carriers, 2932 underwent oophorectomy at a mean age of 45 years; 66% of BRCA1 and 72% of BRCA2 carriers opted for preventive oophorectomy, but only 31% had their ovaries removed by the recommended age (40 years for BRCA1 and 45 years for BRCA2).
• After a mean follow-up of 9 years, 901 cancers were noted in 851 women, and 228 women had died (57 of ovarian or fallopian tube cancer, 58 of breast cancer, 16 of peritoneal cancer, and 97 of other causes).
• Preventive bilateral oophorectomy was associated with a 68% lower risk for death from any cause in women with BRCA1/2 pathogenic variants (hazard ratio [HR], 0.32). The benefit of oophorectomy varied by BRCA status, with a 72% lower risk for all-cause mortality in BRCA1 carriers (HR, 0.28) and 57% lower risk in BRCA2 carriers (HR, 0.43).
• In women with BRCA1 variations, cumulative mortality from all causes to age 75 years fell from 62% to 25% for women who had their ovaries removed at age 35 years compared to those who retained their ovaries. The reduction for women with BRCA2 variations was smaller but substantial (28%-14%).
• In women with BRCA1 variations, oophorectomy had a modest but significant effect on the incidence of breast cancer (HR, 0.79).

IN PRACTICE:

The data "support the current National Comprehensive Cancer Network guidelines" on preventive bilateral oophorectomy for women with BRCA1/2 sequence variations, the researchers said.

"More must be done to increase the identification of carriers of pathogenic variants in BRCA1/2. While genetic testing rates have increased over time, there are still many eligible individuals, both with and without a cancer diagnosis, who are not getting genetic testing completed," editorialists added.

SOURCE:

The study, with first author Joanne Kotsopoulos, PhD, with Women's College Research Institute, University of Toronto, Toronto, Ontario, Canada, and related editorial, was published online on February 29 in JAMA Oncology.

LIMITATIONS:

The causes of death were reported by the study center or next of kin and were not confirmed by medical records or death certificates. This was an observational study, and oophorectomy was by patient choice. Mean duration of follow-up was 9 years; ideally, all participants would be followed up until age 75 years.

DISCLOSURES:

The study was funded by a Canadian Cancer Society Research Institute grant, the Peter Gilgan Foundation, and the Norwegian Cancer Society. The authors and editorialists had no relevant conflicts of interest.