January 12, 2018
Endocrine therapy uses hormone antagonists to greatly reduce the risk of disease recurrence in women with early-stage, estrogen-receptor (ER) positive breast cancer. However, the treatment can come with severe side effects. Around 30 per cent of women stop taking the therapy after three years largely due to these negative impacts. Usually patients receive the hormone therapy for five years following initial treatment (e.g., chemotherapy, surgery), but it can also be taken longer-term. A central question facing patients and clinicians is how to balance, in their decision making, the side effects of long-term treatment with the potential reduction in recurrence risk. In short, they want to know: ‘is it worth it?’
A group of statisticians has now reported the results of a large-scale study that looks to help inform such decision making, as well as well as provide more personalized treatment insights based on research. The study looked at the results of 88 clinical trials with a total of nearly 63,000 participants. Recently published in The New England Journal of Medicine, it reveals that the annual risk of recurrence remains constant for ER-positive patients over a 20-year period following a standard course of endocrine therapy. Extending endocrine therapy from five to 10 years results in an absolute risk reduction of about two per cent, meaning that only one in 50 women will actually benefit from prolonged endocrine therapy.
Dr. John Bartlett, Director of OICR’s Diagnostic Development Program, serves on the steering committee of the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), which conducted the study. “Unfortunately, this study confirms that there is an initial peak of risk of recurrence after 2-3 years and that the risk plateaus after the peak and stays with the patient, at the same annual risk, for at least 20 years. This is the first robust evidence we have of this,” says Bartlett. The study also found that risk of recurrence was strongly associated with the size of the breast cancer tumour and if there was lymph node involvement. Bartlett is currently involved in the development of biomarkers that can help determine a patient’s level of risk for recurrence and also the benefit that they will receive from longer duration endocrine therapy.
ER-positive breast cancer accounts for 80 per cent of breast cancer cases and causes more deaths than any other form of the disease. “What this study also tells us is that there is more work to do when it comes to ER-positive breast cancers and decision making around endocrine therapy,” says Bartlett, noting that many women who are on endocrine therapy long-term become locked into constant menopause and experience many side effects. “This study bolsters the view that we need better ways to determine which patients’ risk levels necessitate long-term usage and those that can likely forgo extended endocrine therapy.”
The biomarkers under development by Bartlett and his collaborators aim to help determine the best course of treatment. “We have been working with teams in the U.K. and U.S. to develop tools to answer the main questions that should guide extended endocrine therapy,” explains Bartlett. “If we can tell patients their level of risk and how much benefit they will get from the therapy it puts them and their physicians in a better place to decide on length of treatment.”