The data showed that women benefited from taking the drug letrozole, part of a class of estrogen-reducers called aromatase inhibitors, for 10 years. Typically, that kind of drug is taken for five years, sometimes after a course of tamoxifen, which acts as an anti-estrogen drug in the breast.
While many women with early-stage breast cancer live for a long time, they “face an indefinite risk of relapse,” said the study's lead author, Paul Goss, director of breast cancer research at Massachusetts General Hospital. He said the new research "provides direction for many patients and their doctors, confirming that prolonging aromatase inhibitor therapy can further reduce the risk of breast cancer recurrences."
However, women who were treated with the drug for a total 10 years didn't live longer than those who were given a placebo in the study. Goss said at a news briefing on Sunday that he's confident a survival benefit will emerge in the data in coming years.
The results of the study were published online in the New England Journal of Medicine, which also featured an editorial calling the study "reassuring" and saying that "the findings have direct application for clinical practice."
But some experts were cautious about predicting changes in treatment strategies. Letrozole has side effects, and the women who took it for a prolonged period as part of the study suffered more bone pain, fractures and the onset of osteoporosis compared with the women who didn't get the drug.
Those side effects, as well as the absence of a survival benefit, means doctors and patients will have to carefully weigh the risks and benefits of taking an aromatase inhibitor for a decade, said J. Leonard Lichtenfeld, deputy chief medical officer for the American Cancer Society who wasn't involved in the research. The study itself, he said, does not offer "as clear a result as one might like."
Claudine Isaacs, a medical oncologist at Georgetown University’s Lombardi Comprehensive Cancer Center, said the data was long-awaited by clinicians who wondered whether prolonged treatment with aromatase inhibitors would be beneficial and safe for patients.
“This gives us data to take back to the clinic to talk to our patients about,” said Isaacs, who led Lombardi's participation in the study. “If I had a patient who doesn’t have side effects from this therapy and has a higher risk of recurrence, I’d consider extending it — or at least having an informed discussion with her.”
The study enrolled 1,918 postmenopausal women in the randomized Phase 3 trial. All had taken letrozole for about 5 years; some also had been treated previously with tamoxifen. Half of the women were given a daily pill of letrozole for an additional 5 years, while the rest were put on a placebo. At a six-year followup, a total of 165 women had experienced a recurrence of breast cancer or developed a new cancer in the opposite breast. Of those, 67 were in the letrozole group while 98 were in the placebo group.
That meant the risk of disease recurrence and new cancer was 34 percent lower among women who continued the aromatase inhibitor for 10 years compared with the other group, researchers said. Looked at another way, 95 percent of the women in the letrozole group experienced disease-free survival for five years, compared with 91 percent in the placebo group.
Currently, when older women develop breast cancer, they are prescribed a variety of regimens to reduce the possibility of recurrence, including taking tamoxifen for five or 10 years, some combination of tamoxifen and an aromatase inhibitor, or an aromatase inhibitor alone for five years.
Clinicians knew from previous studies that using tamoxifen for up to 10 years was better than using it for five years, but there wasn’t corresponding data for aromatase inhibitors.
Harold Burstein, a medical oncologist at Dana-Farber Cancer Institute and a spokesman for the oncologists' group, acknowledged that “10 years of any therapy is a long time.” But he said he expected there to be "tremendous interest" in the study.