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Letrozole, After Tamoxifen, Reduces Risk for Breast Cancer Recurrence

After 5 years of tamoxifen therapy, a course of letrozole reduced breast cancer recurrence even further.

After surgery for hormone-receptor-positive breast cancer, a 5-year course of tamoxifen reduces risks for recurrence and for contralateral breast cancer. Continuing tamoxifen therapy beyond 5 years confers no additional benefit, yet breast cancer sometimes recurs after this interval. In this double-blind, randomized, partially manufacturer-supported trial, researchers examined whether the aromatase inhibitor letrozole prevents late recurrences. Aromatase inhibitors block the synthesis of estrogens from androgens.

More than 5000 postmenopausal women who had completed 5 years of tamoxifen therapy for hormone-receptor-positive breast cancer and who had no evidence of recurrence received either letrozole (2.5 mg daily) or placebo. The investigators intended to treat patients for 5 years, but the trial was interrupted after a median follow-up of 2.4 years (based on a planned interim analysis). At that point, estimated 4-year disease-free survival was significantly greater in the letrozole group than in the placebo group (93% vs. 87%). More than half of the 207 recorded recurrences were distant metastases. Fewer deaths occurred in the letrozole group (31 vs. 42), although the difference was not significant. Compared with placebo recipients, letrozole recipients more commonly reported hot flashes, arthralgias, arthritis, and myalgias but less commonly reported vaginal bleeding.

Comment: These data show convincingly that letrozole, given after a 5-year course of tamoxifen, reduces the incidence of recurrent breast cancer in postmenopausal women. Some people have criticized the early termination of this study because letrozole's optimal duration of treatment, its effect on mortality, and long-term risks for osteoporosis and cardiovascular disease remain unclear. Two editorialists (Bryant and Wolmark) discuss the controversy over early termination of this trial, and another (Burstein) discusses individualizing these results for patients. At the time of publication, the full text of the original article was available free of charge.

— Allan S. Brett, MD

Published in Journal Watch General Medicine October 31, 2003

Citation(s):

Goss PE et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003 Nov 6; 349:1793-802.

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• Medline abstract (Free)

Bryant J and Wolmark N. Letrozole after tamoxifen for breast cancer -- What is the price of success? N Engl J Med 2003 Nov 6; 349:1855-7.

• Original article (Subscription may be required)
• Medline abstract (Free)

Burstein HJ. Beyond tamoxifen -- Extending endocrine treatment for early-stage breast cancer. N Engl J Med 2003 Nov 6; 349:1857-9.

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• Medline abstract (Free)