Breast cancer recurrence risk lingers years after treatment ends
Even 20 years after a diagnosis, women with a type of breast cancer fueled by estrogen still face a substantial risk of cancer returning or spreading, according to a new analysis from an international team of investigators published in the New England Journal of Medicine.
Standard treatment for estrogen receptor-positive, or ER-positive, breast cancer includes five years of the endocrine-based treatments tamoxifen or aromatase inhibitors, both of which are a taken daily as a pill.
Researchers from the Early Breast Cancer Trialists’ Collaborative Group analyzed data from 88 clinical trials involving 62,923 women with ER-positive breast cancer. The patients all received endocrine therapy for five years and were free of cancer when they stopped therapy.
Over the next 15 years, however, a steady number of these women saw their cancer metastasize (spread) throughout the body, as late as 20 years after the initial diagnosis.
Even though these women remained free of recurrence in the first five years, the risk of having their cancer recur in the bone, liver or lung from years five to 20 remained constant.
The risk of recurrence was directly tied to the original cancer’s size and characteristics, and to the number of lymph nodes that were cancerous. The highest risk of recurrence was among women with large tumours and four or more involved axillary nodes, who had a 40% risk of distant cancer recurrence by year 20. Women with small low-grade cancers and no spread to the nodes had a much lower 15-year risk of distant spread of 10%.
“This study further demonstrates that breast cancer is not all one disease but is comprised of different subtypes with different natural histories,” said Dr. Kathy Pritchard, researcher at Sunnybrook Health Sciences Centre and a medical oncologist. “While all women with ER-positive disease have an ongoing risk of recurrence, their initial tumour characteristics can predict the degree of risk after the initial five years of endocrine therapy, allowing personalized management of their ongoing endocrine management.”
Studies have shown that five years of tamoxifen reduces recurrence by half during treatment and by nearly a third over the next five years. Aromatase inhibitors, which work only in post-menopausal women, are even more effective than tamoxifen at reducing recurrence and death from breast cancer.
Doctors have long known that five years of tamoxifen reduces recurrence by approximately half during treatment, and by nearly a third over the next five years. Aromatase inhibitors, which work only in post-menopausal women, are even more effective than tamoxifen at reducing recurrence and death from breast cancer.
Newer studies have suggested an additional five years of endocrine therapy is even more effective than five years, sparking the question of whether every woman should continue on this therapy beyond 5 years.
Life-threatening side effects are rare with these therapies, but they can impact patients’ quality of life. Side effects mimic menopausal symptoms, such as hot flashes or vaginal dryness. Aromatase inhibitors can cause osteoporosis, joint pain or carpal tunnel syndrome. Studies suggest that some patients stop taking endocrine therapy because of these side effects.
“As we look at extending endocrine therapy for 10 years, we wanted to determine whether there were certain subgroups of women whose risk of recurrence was so low they might not need to continue endocrine therapy after five years,” says senior study author Daniel F. Hayes, M.D., Stuart B. Padnos Professor of Breast Cancer Research at the University of Michigan Comprehensive Cancer Center.
The researchers subdivided patients to analyze those with the best prognosis – small tumours with less-aggressive properties and no positive lymph nodes. Even these women had appreciable recurrence rates between years five and 20, at almost one percent per year, or 10 percent over the course of 15 years.
The data suggest that all women with ER-positive breast cancer should at least consider taking anti-estrogen therapy beyond five years, the authors say. They point out, though, that this analysis is based on trials conducted many years ago and may not be completely accurate for women diagnosed more recently.
“We hope patients and their health care providers will use these data —weighed against side effects and toxicity of the therapies — to inform their discussions around taking anti-estrogen therapy beyond five years,” Dr. Pritchard says. “Speak to your care team.”
Additional authors: Hongchao Pan, Richard Gray, Jeremy Braybrooke, Christina Davies, Carolyn Taylor, Paul McGale, Richard Peto, Jonas Bergh, Mitch Dowsett
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