Ovary and fallopian tube removal linked to lower death risk in BRCA carriers with breast cancer

Women diagnosed with breast cancer who carry particular BRCA1 and BRCA2 genetic variants are offered surgery to remove the ovaries and fallopian tubes as this dramatically reduces their risk of ovarian cancer.

Now, Cambridge researchers have shown that this procedure – known as bilateral salpingo-oophorectomy (BSO) – is associated with a substantial reduction in the risk of early death among these women, without any serious side-effects.

Women with certain variants of the genes BRCA1 and BRCA2 have a high risk of developing ovarian and breast cancer. These women are recommended to have their ovaries and fallopian tubes removed at a relatively early age – between the ages 35 and 40 years for BRCA1 carriers, and between the ages 40 and 45 for BRCA2 carriers.

Previously, BSO has been shown to lead to an 80% reduction in the risk of developing ovarian cancer among these women, but there is concern that there may be unintended consequences as a result of the body's main source of oestrogen being removed, which brings on early menopause. This can be especially challenging for BRCA1 and BRCA2 carriers with a history of breast cancer, as they may not typically receive hormone replacement therapy to manage symptoms. The overall impact of BSO in BRCA1 and BRCA2 carriers with a prior history of breast cancer remains uncertain. 

Ordinarily, researchers would assess the benefits and risks associated with BSO through randomised controlled trials, the 'gold standard' for testing how well treatments work. However, to do so in women who carry the BRCA1 and BRCA2 variants would be unethical as it would put them at substantially greater risk of developing ovarian cancer.

To work around this problem, a team at the University of Cambridge, in collaboration with the National Disease Registration Service (NDRS) in NHS England, turned to electronic health records and data from NHS genetic testing laboratories collected and curated by NDRS to examine the long-term outcomes of BSO among BRCA1 and BRCA2 PV carriers diagnosed with breast cancer. The results of their study, the first large-scale study of its kind, are published today in The Lancet Oncology.

The team identified a total of 3,400 women carrying one of the BRCA1 and BRCA2 cancer-causing variants (around 1,700 women for each variant). Around 850 of the BRCA1 carriers and 1,000 of the BRCA2 carriers had undergone BSO surgery.

Women who underwent BSO were around half as likely to die from cancer or any other cause over the follow-up period (a median follow-up time of 5.5 years). This reduction was more pronounced in BRCA2 carriers compared to BRCA1 carriers (a 56% reduction compared to 38% respectively). These women were also at around a 40% lower risk of developing a second cancer.

Although the team say it is impossible to say with 100% certainty that BSO causes this reduction in risk, they argue that the evidence points strongly towards this conclusion.

Importantly, the researchers found no link between BSO and increased risk of other long-term outcomes such as heart disease and stroke, or with depression. This is in contrast to previous studies that found evidence in the general population of an association between BSO and increased risk of these conditions.

First author Hend Hassan, a PhD student at the Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, and Wolfson College, Cambridge, said: "We know that removing the ovaries and fallopian tubes dramatically reduces the risk of ovarian cancer, but there's been a question mark over the potential unintended consequences that might arise from the sudden onset of menopause that this causes.

"Reassuringly, our research has shown that for women with a personal history of breast cancer, this procedure brings clear benefits in terms of survival and a lower risk of other cancers without the adverse side effects such as heart conditions or depression."

Most women undergoing BSO were white. Black and Asian women were around half as likely to have BSO compared to white women. Women who lived in less deprived areas were more likely to have BSO compared to those in the most-deprived category.

Hassan added: "Given the clear benefits that this procedure provides for at-risk women, it's concerning that some groups of women are less likely to undergo it. We need to understand why this is and encourage uptake among these women."

Our findings will be crucial for counselling women with cancer linked to one of the BRCA1 and BRCA2 variants, allowing them to make informed decisions about whether or not to opt for this operation."

Professor Antonis Antoniou,  study's senior author, Department of Public Health and Primary Care

Professor Antoniou, who is also Director of the Cancer Data-Driven Detection programme, added: "The study also highlights the power of exceptional NHS datasets in driving impactful, clinically relevant research."

The research was funded by Cancer Research UK, with additional support from the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre.