Risk-reducing ovarian surgery in women with BRCA1/BRCA2-related breast cancer

Women who have inherited a harmful variant in their BRCA1 or BRCA2 genes are at high risk of developing breast and ovarian cancer. To help reduce the ovarian cancer risk*, these women are usually offered surgical removal of the ovaries and fallopian tubes (known medically as ‘bilateral salpingo-oophorectomy’, or ‘BSO’) around the age of 35-45. This operation results in a surgically-induced early menopause, and there were concerns that this sudden and permanent drop in female hormones might put these women at risk of other illnesses, such as heart disease.

*Ovarian cancer is a broad term that includes tumours arising from the ovary, Fallopian tube or peritoneum (the membrane that lines the abdominal and pelvic cavity and covers the internal organs). The BSO operation removes the ovaries and Fallopian tubes, but cannot remove the peritoneum, so a small risk of primary peritoneal cancer remains.

Early menopause is usually treated with hormone replacement therapy (HRT); however HRT is not usually an option for women who have already had breast cancer, as oestrogen can encourage breast cancer cells to grow. So, the question remained: how should we best care for female BRCA1/BRCA2 carriers with a personal history of breast cancer? Was offering the BSO operation helpful, or were its benefits outweighed by the potential harms of the resulting early menopause?

Questions like these are usually addressed by carrying out a clinical trial, but this was not possible, as it would be unethical to withhold a potentially life-saving intervention (BSO) from some trial participants. There was a pressing need to gather high quality scientific evidence in an ethical way.

The uncertainty has now been resolved by using NHS data, in a collaboration between NDRS and the University of Cambridge. The research was published in The Lancet Oncology on 8May 2025.

In NDRS, as well as holding national data on cancer diagnosis and survival, we collect genetic testing data on cancer predisposition genes from NHS laboratories across the country. By linking these two NDRS datasets together, it was possible to identify 3,400 women with breast cancer who had harmful genetic variants in their BRCA1 or BRCA2 genes. NDRS data on these women was linked with the Hospital Episode Statistics (HES) dataset to identify which of them had undergone BSO; their long-term outcomes were gathered from HES and NDRS data.

Looking at outcomes over an average (median) follow up time of 5.5 years, women who had undergone BSO were shown to have a 40% lower risk of developing a second cancer, and a 50% reduction in death from any cause. BSO was not associated with adverse outcomes (e.g. depression, heart disease or stroke) in this group of women.

This is clinically important evidence that, at population-level, the benefits of BSO outweigh the potential harms in this group of women. The work has resolved a significant area of uncertainty around existing (but previously unproven) clinical practice; it will enable genetic counsellors to give clearer information to the women most vulnerable to breast and ovarian cancer, and allow these women to make more informed personal decisions.

The study also revealed that women of Black or Asian ethnicity were around half as likely to undergo BSO as compared to White women. This finding will help the NHS to target resources to address inequalities.