Use of the aromatase inhibitor letrozole after completion of an initial 5-year course of tamoxifen significantly reduces risk for recurrent breast cancer in postmenopausal women with early-stage disease, according to an article published in the October 9th advance online issue of the New England Journal of Medicine. The international study, which randomized 5,187 women to letrozole or placebo after completion of tamoxifen therapy, was stopped early because of the positive results.

A total of 207 women (132, placebo group; 75, letrozole) developed recurrent disease. At 4 years, 13 percent of women on placebo versus 7 percent on letrozole had recurrent disease --- a decrease in risk with letrozole of 43 percent. Deaths from breast cancer were also reduced, with 17 deaths in the placebo group and 9 in the letrozole group.
“More than half of women who develop recurrent breast cancer do so more than five years after their original diagnosis,” said Paul Goss, M.D., lead author of the study. “For years, we have thought that we had reached the limit of what we could do to reduce the risk of recurrence with five years of tamoxifen. Our study ushers in a new era of hope by cutting these ongoing recurrences and deaths from breast cancer after tamoxifen by almost one half.” Goss, a leading expert in novel hormone therapies for prevention and treatment of breast cancer, developed and chaired the current trial.

Coauthor James Ingle, M.D., said, “Based on our findings, all post-menopausal women with hormone-receptor positive tumors completing about five years of tamoxifen should discuss taking letrozole with their doctors to reduce their risk of breast cancer recurrence.”

Women participated in the study for an average of 2.4 years and for as long as 5 years. The study found that women in the letrozole group had a reduction in the number of recurrences of cancer in the previously affected breast, a reduction in the number of new cancers in the opposite breast, and a reduction in the development of metastatic disease.

The side effects of letrozole, which was taken once a day, are very similar to those experienced during natural menopause; side effects were generally mild in study participants. Women in the study will continue to be followed to assess any effects of long-term use of letrozole on bone or other organs.