Letrozole boosted survival and should be first-line treatment, experts say
WEDNESDAY, Aug. 19 (HealthDay News) -- For postmenopausal women with breast cancer, treatment with the drug letrozole (Femara) increases survival after surgery more than the widely used tamoxifen, a new study confirms.
Both letrozole and tamoxifen have been used to prevent recurrence of breast cancer in postmenopausal women with hormone receptor-positive cancer, but whether one drug is better than the other has been unclear. The new study compared the impact of the newer drug, letrozole, to tamoxifen.
"This study reinforces the benefits of letrozole over tamoxifen, and leaves five years upfront use [of letrozole] as the preferred option, especially in patients judged to be at higher risk for recurrence," said lead researcher Dr. Alan Coates, co-chair of the scientific committee of the International Breast Cancer Study Group and a clinical professor in the School of Public Health at the University of Sydney, Australia.
The report is published in the Aug. 20 issue of the New England Journal of Medicine.
For the study, Coates and colleagues randomly assigned more than 8,000 postmenopausal women with hormone receptor-positive breast cancer to treatment with tamoxifen or letrozole for five years. In addition, some of the women were assigned to switch medicines after two years.
The study shows strong, though not incontrovertible, evidence that letrozole prolongs overall survival in comparison to tamoxifen, and that "this would in all probability have been conventionally significant had the switch of therapy not occurred," Coates said.
The other question in the study was whether the letrozole should be given before or after a period of tamoxifen therapy, Coates said.
"Neither sequence was superior to five years of straight letrozole," he said. "We found that the differences were small, but that consistently in the higher risk subgroups there was a benefit to starting with letrozole."
The study also included starting with letrozole and switching to tamoxifen, Coates noted.
"The difference between straight letrozole and the reverse sequence was very small in all groups, which will be reassuring to those women who, having started adjuvant treatment with letrozole, are obliged for any reason to discontinue that drug. Our data suggest that they can safely switch to tamoxifen if required with little or no harm to their prognosis," he said.
Both drugs are used after initial treatment to prevent the cancer from returning. The medications work by preventing the production or activity of estrogen, which is associated with breast cancer recurrence in postmenopausal women. The drugs work differently, which may account for the benefit of letrozole over tamoxifen. Letrozole is from a class of drugs called aromatase inhibitors, which block the production of estrogen. Tamoxifen differs in that it interferes with the activity of estrogen, not the hormone's production.
Dr. Victor Vogel, national vice president of research at the American Cancer Society, believes that because letrozole is more effective and has fewer side effects than tamoxifen, it should be used for most patients.
"The message to lay people is letrozole is better. That's the unequivocal, unconfused message," Vogel said. "If you are a postmenopausal women taking tamoxifen for early breast cancer, it's probably a good idea to switch from tamoxifen to letrozole."
However, tamoxifen should be used for patients who find it difficult to take letrozole, Vogel said. "Somewhere between 15 and 25 percent of patients get significant muscle aches and joint aches with aromatase inhibitors. For those patients, tamoxifen is still a reasonable thing to do."
Dr. Larry Norton, deputy physician-in-chief of Breast Cancer Programs at Memorial Sloan-Kettering Cancer Center in New York City, said the study shows no advantage in starting women on tamoxifen and then switching them to letrozole.
"For postmenopausal people, it becomes clearer and clearer that the treatment of choice is an aromatase inhibitor without the use of tamoxifen," Norton said. "The window of opportunity for tamoxifen is narrowed by this paper."
"For most patients who are postmenopausal, I use an aromatase inhibitor exclusively," Norton added. "But I have used tamoxifen in postmenopausal patients for specific situations, such as extremity fragile bones, or such as intolerance of the aromatase inhibitor."
There's more on breast cancer at the American Cancer Society.
SOURCES: Alan Coates, M.D., co-chair, scientific committee, International Breast Cancer Study Group, and clinical professor, School of Public Health, University of Sydney, Australia; Larry Norton, M.D., deputy physician-in-chief, Breast Cancer Programs, Memorial Sloan-Kettering Cancer Center, New York City; Victor Vogel, M.D., M.H.S., national vice president, research, American Cancer Society; Aug. 20, 2009, New England Journal of Medicine
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