Memorial Sloan-Kettering breast cancer specialist Clifford Hudis discusses the results of an international clinical trial that has the potential to change current treatment practice for certain women with breast cancer.
New, potentially practice-changing research is shedding light on the long-term benefits of estrogen-blocking tamoxifen therapy in women with early-stage breast cancer whose disease is also estrogen-receptor (ER) positive. The findings of a large study, which involved more than 6,800 women with ER-positive disease, may lead doctors to advise such patients to continue taking tamoxifen beyond the current recommendation of five years.
The collaborative international study, known as ATLAS, was led by researchers at the University of Oxford and was presented today at the San Antonio Breast Cancer Symposium – an annual conference where the latest information on breast cancer research and treatment is shared among thousands of physicians and scientists in the field. The research has also been published today in The Lancet.
To better understand the study’s findings and clinical implications, we spoke with medical oncologist Clifford A. Hudis, Chief of the Breast Cancer Medicine Service at Memorial Sloan-Kettering and President-Elect of the American Society of Clinical Oncology.
What is tamoxifen?
Breast cancer cells that have receptors for the hormone estrogen are called estrogen-receptor (ER) positive and are more likely to respond to therapy with anti-estrogen medications such as tamoxifen – an FDA-approved drug that acts by blocking estrogen from feeding estrogen-dependent cancer cells.
The drug is known to greatly reduce the risk of a breast cancer returning, also known as recurrence, as well as the risk of death from the disease. Tamoxifen also has the added benefit of preventing a new breast cancer from developing and may treat or prevent osteoporosis – a common condition among older women in which bones become more fragile and more likely to fracture.
What is the current standard of care for women with early-stage ER-positive breast cancer?
The current recommendation for women who have already been treated with surgery and/or radiation therapy calls for five years of follow-up treatment with tamoxifen. Up until now, it was unclear how extending treatment with tamoxifen from five years to ten years affected patient outcomes in the decades after diagnosis.
What did the ATLAS study find?
Women in the study had approximately five years of tamoxifen therapy after their initial surgery and/or radiation therapy. They were randomly assigned to either continue the therapy for another five years or to stop at year five.
Researchers followed the women over time and found that those who continued to take tamoxifen for a total of ten years were further protected against breast cancer recurrence and, particularly during the second decade, death from breast cancer. An additional analysis projected that breast cancer deaths would be reduced by at least one-third 15 years after diagnosis among women who take tamoxifen for a total of ten years.
Are there any added risks to taking tamoxifen for a longer period of time?
There is a small risk of uterine cancer among women who take tamoxifen for five years — about one in 500. The study did find that postmenopausal women over age 50 may have a slightly higher risk of developing uterine cancer if they continue treatment for an additional five years. On the other hand, there was no apparent higher risk of uterine cancer among premenopausal women who continued to take the drug.
Do you think the results of this study will change the way breast cancer is managed?
The observations gleaned from this important study do support extending the duration of tamoxifen beyond the current five-year recommendation. However, I believe longer follow-up and more-detailed analysis of ATLAS is necessary to more reliably assess the apparently substantial decrease in breast cancer deaths in the second decade after diagnosis and possibly change how we manage patients.
It’s worth mentioning that these findings could have the greatest impact on younger, premenopausal women with ER-positive breast cancer who are at higher risk of recurrence and currently have no alternative treatment options after the first five years of tamoxifen therapy — whereas postmenopausal women can be offered another class of drugs called aromatase inhibitors, which interferes with the production of estrogen.
Women with breast cancer should discuss with their doctor the benefits and risks of tamoxifen and how its use might affect their own health.