Letrozole following tamoxifen extends breast ca survival.(News)

SAN ANTONIO -- Women with hormone receptor-positive early-stage breast cancer gain substantial clinical benefit from starting an aromatase inhibitor even following a 1- to 5-year hiatus after a 5-year course of adjuvant tamoxifen, according to an updated analysis of the landmark National Cancer Institute of Canada MA.17 trial.

"Women with hormone-dependent breast cancer prescribed letrozole after a prolonged delay from completing tamoxifen experienced a significant improvement in disease-free survival, distant disease-free survival, and overall survival and should be considered for this therapy in the clinic," said Dr. Paul E. Goss at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

The once-standard 5 years of adjuvant tamoxifen isn't good enough, according to Dr. Goss. The MA.17 trial has shown that a substantial and indeed steadily increasing risk of disease recurrence exists in the years following completion of tamoxifen therapy, he said. Dr. Goss is director of breast cancer research at Massachusetts General Hospital and professor of medicine at Harvard Medical School, Boston.

MA.17 was the first major clinical trial involving extended adjuvant therapy with an aromatase inhibitor (AI). It involved 5,187 postmenopausal women with hormone receptor-positive early breast cancer who completed 5 years of adjuvant tamoxifen and then were randomized in double-blind fashion to a planned 5 years of the AI letrozole (Femara) at 2.5 mg/day or placebo. The study was unblinded early--in October 2003, a median 30 months after randomization--when an interim analysis showed the letrozole group had a 42% reduction in the risk of disease recurrence as described in a recent publication covering the period up to the unblinding (J. Natl. Cancer Inst. 2005;97:1262-71).

Dr. Goss presented an update on what's happened in MA.17 since the unblinding. At that point, patients in the placebo arm were informed of the results and given the option of switching to letrozole; 1,655 did so, and 613 others opted for no further therapy. The update did not include the nearly 2,500 patients who had been randomized to letrozole and elected to continue on the drug for the planned 5 years.

During the median 2 years' follow-up since the unblinding, 1.5% of patients who opted for no therapy have developed a new primary breast cancer, compared with 0.2% of women who switched to letrozole after 1-5 years on placebo. The rates of contralateral breast cancer and both local-regional and distant recurrences were also significantly higher in the no-therapy group. (See graph.)

Mortality due to breast cancer occurred in 0.8% of the no-therapy group, a rate twice that of women who switched to letrozole. Death due to other causes occurred in 1% of the no-therapy group and 0.5% of those who made the switch from placebo to the AI. These mortality differences were statistically significant.