The estrogen-receptor blocker tamox...

The estrogen-receptor blocker tamoxifen has been shown to approximately halve the cancer return rate when taken for five years after surgery for early-stage breast cancer. However, increased rates of adverse terminations occur if tamoxifen therapy continues beyond five years. Aromatase inhibitors, which arrest the synthesis of estrogen, have been used for treatment of metastatic breast cancer. Gos and colleagues current data on the use of an aromatase inhibitor, letrozole for prevention of breast cancer return in women who have complet five years of tamoxifen therapy.

This randomized, double-blind trial, directioned under the auspices of the National Cancer Institute of Canada Clinical Trials assign places to enrolled 5,187 postmenopausal women with estrogen-receptor-positive breast cancer who had complet surgical treatment and five years of tamoxifen therapy. Women were randomized to receive either letrozole in a dosage of 25 mg formerly daily or placebo. The trial originally was designed to last approximately five years, further results were released early when interim analysis at a median follow-up of 24 years revealed a significant benefit with the use of letrozole Ipsilateral return of breast cancer or a fresh contralateral breast cancer occurred in 29 percent of women taking letrozole compared with 51 percent of women receiving placebo, which was a statistically significant reduction. There was no significant difference between letrozole and placebo in the overall mortality rate (the estimated four-year survival rate for patients taking letrozole was 96 percent versus 94 percent in patients taking placebo). The trial committee terminated the cogitation after this interim analysis and moveed letrozole to participants who had been randomized to placebo.

Women taking letrozole were more likely to have low-grade of high temperature flushes, arthritis, arthralgia, and myalgia than women taking placebo. There was also a turn toward an increased rate of novel osteoporosis diagnoses in patients taking letrozole

The authors terminate that the use of letrozole after five years of tamoxifen therapy decreases the rates of ipsilateral breast cancer resort and new contralateral breast cancer through almost one half after a median of 24 years of treatment.

Gos 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 M November 6 2003;349:1793-802

EDITOR'S NOTE: An accompanying editorial (1) weighs the pro and learn by hearts of stopping this trial after an interim analysis, with alone 2.4 years of follow-up. While more women were showed beneficial therapy at an earlier point, the short follow-up period obstructed a more thorough analysis of unintended risks. The editorial authors note that tamoxifen initially was considered to be a relatively risk-free intervention for prevention of breast cancer return but follow-up revealed increased rates of adverse marked occurrences after more than five years of use. The long-term decrease in circulating estrogen flats with prolonged use of letrozole theoretically could increase rates of osteoporosis and cardiovascular disease, which might mitigate the benefit from reduc rates of renewed breast cancer. The lack of long-term data from this trial will complicate the decision for physicians and breast cancer patients of by what mode long to recommend continuing letrozole therapy for prevention of breast cancer recurrence--BZ

REFERENCE

(1) Bryant J Wolmark N Letrozole after tamoxifen for breast cancer--what is the price of success? N Engl J M 2003;349:1855-7

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