A new study by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) has found that suppressing ovarian function can further reduce the risk of breast cancer recurrence by one-fifth in premenopausal women who are also taking tamoxifen.
For younger women with breast cancer, shutting down the ovaries' production of oestrogen can significantly reduce the risk of the cancer coming back, and can save lives, according to the largest ever analysis of ovarian function suppression (OFS) in breast cancer, published today in The Lancet.
Ovarian function suppression is most commonly achieved temporarily using drug injections, meaning ovarian function can recover afterwards, or can be done permanently through surgery or radiotherapy. OFS is one of the oldest treatments used for breast cancer and earlier studies by the EBCTCG have shown it to be effective in reducing the risk of recurrence but it was not known how well it would work alongside other treatments such as tamoxifen or chemotherapy.
Tamoxifen, a drug that blocks oestrogen's effects, is already a standard treatment for hormone-sensitive breast cancer and roughly halves the risk of recurrence. But even in women who are treated with tamoxifen, the risk of the cancer returning remains real and persists for at least 20 years after diagnosis.
In this study, researchers collected data from around 15,000 women across 23 clinical trials spanning more than 70 years. They found that, for premenopausal women with hormone-sensitive early breast cancer who were already taking tamoxifen, adding OFS further reduced the risk of recurrence by about one fifth. For women under 45, the benefit was even greater: OFS cut the risk of recurrence and of dying from breast cancer by around one quarter.
The researchers found that OFS adds meaningful benefit but only for women who are premenopausal when they start it. That distinction matters because chemotherapy itself can trigger an early menopause in some women, and giving OFS to someone whose ovaries have already stopped working offers little or no additional effect.
For women confirmed to be premenopausal, either because they hadn't had chemotherapy, or because their menopausal status was checked afterwards, the benefits were clear and sustained over long periods of time:
-
Adding OFS to tamoxifen reduced recurrence rates by about one fifth, leading to an absolute 5.9 percent lower 15-year recurrence risk;
-
In women under 45, OFS reduced distant recurrence (cancer in another part of the body), breast cancer deaths, and overall deaths each by roughly one quarter;
-
OFS benefitted women regardless of whether they had already received chemotherapy, as long as they were still premenopausal when starting OFS;
-
Benefits were seen consistently across the first and second decades after treatment, not just in the short term;
-
OFS did not increase deaths from other causes or raise the risk of developing other cancers.
‘These findings are directly relevant to the growing number of younger women being diagnosed with breast cancer. It hasn't been clear whether ovarian function suppression adds benefit on top of chemotherapy and tamoxifen – now we know it does, and for women under 45 those benefits are substantial,’ said Rosie Bradley, senior statistician at Oxford Population Health and statistician for the study.
Previous studies conducted by EBCTCG have shown that combining OFS with aromatase inhibitors, drugs that block oestrogen production elsewhere in the body, is even more effective than OFS with tamoxifen. Together these results suggest that for many younger women with hormone-sensitive early breast cancer, the most effective approach may be a combination of OFS alongside an aromatase inhibitor.
‘Only by combining all the available trial evidence in an analysis like this can we give women and their doctors the most reliable picture. These results will inform real treatment decisions, and help women weigh the benefits of OFS against the potential side-effects,’ added Dr Jeremy Braybrooke, Senior Clinical Research Fellow, Oxford Population Health, Consultant Medical Oncologist, and one of the study’s authors.
Sophie Conway, Head of Policy and Engagement, CoppaFeel!, said ‘These findings are an important step in helping younger women with hormone-sensitive breast cancer better understand their treatment options. But they also highlight how important it is for research to capture the lived experience of patients. Treatments like ovarian function suppression can profoundly impact women's quality of life, fertility and long-term health and wellbeing. Future trials should ensure that patient voices and experiences are reflected, so women can fully understand what different treatment options may mean for them.’
Caroline Geraghty, senior specialist nurse manager at Cancer Research UK, said ‘This has been a recommended treatment for some pre-menopausal women with breast cancer for many years, so it's fantastic to see just how big an impact the treatment can have. However, it's important to note that for some women who have ovarian function suppression alongside tamoxifen, they can have menopausal-type side effects, that can be difficult to live with.
‘Knowing the exact benefit of this therapy will help women and their doctors have informed discussions about the treatment options that will give the best risk of lowering their recurrence, while being aware of their impact on quality of life, so they can choose whatever is best for them.’
Dr Dorraya El-Ashry, Chief Scientific Officer at the Breast Cancer Research Foundation (BCRF), said
The findings reported here highlight the importance of these kinds of analyses that only the EBCTCG can conduct. Their impact on informing standard of care is integral to BCRF’s mission of ending breast cancer by advancing the most promising research.
The study was funded by Oxford Population Health, BCRF, and CRUK.