Adjuvant therapy: aromatase inhibitors impressive against breast ca.(Gynecology)

SAN ANTONIO -- Tamoxifen is looking increasingly like "yesterday's drug" for endocrine therapy of early breast cancer.

A newer class of antiestrogens--the aromatase inhibitors--is racking up impressive evidence of superiority over tamoxifen in comparative trials. Questions remain, however, regarding the optimal duration of adjuvant aromatase inhibitor therapy and whether it should be used sequentially with or in lieu of tamoxifen, according to speakers at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Five years of adjuvant tamoxifen after surgery and/or chemotherapy for estrogen receptor-positive early breast cancer has long been standard therapy; it results in greater disease-free and overall survival than when tamoxifen is omitted or prescribed for a shorter duration. But the landscape shifted dramatically when the initial results of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial were presented at the 2002 symposium.

ATAC was a randomized, double-blind clinical trial involving 9,365 postmenopausal women with early breast cancer, making it the largest-ever study in breast cancer treatment. It showed adjuvant anastrozole (Arimidex) was superior to tamoxifen for all major outcomes. And in further studies presented at the 2003 symposium, the aromatase inhibitors anastrozole and letrozole, both approved in the United States, continued to outperform tamoxifen in a variety of settings:

* Switching from tamoxifen to anastrozole. Shifting patients midstream from adjuvant tamoxifen to anastrozole significantly reduces their risk of relapse or death, according to Dr. Francesco Boccardo of the University of Genoa (Italy). He reported on 448 postmenopausal women with node-positive, estrogen receptor-positive breast cancer who were randomized to 5 years of adjuvant tamoxifen at 20 mg/day or to a switch from tamoxifen to 1 mg/day of anastrozole after 2-3 years for the balance of their 5 years of adjuvant endocrine therapy.

During a median follow-up of roughly 3 years, there were 13 cases of local-regional recurrent breast cancer in the tamoxifen-only group, compared with 2 in patients switched to anastrozole. Distant metastases occurred in 19 patients in the tamoxifen-only arm, compared with 10 in the switchers. There were 10 deaths in the tamoxifen-only group and 4 in patients who switched. The likelihood of event-free survival was 64% greater in patients who switched to anastrozole.

In terms of side effects, GI symptoms occurred in 1.3% of patients in the tamoxifen-only group and in 6.3% of those who switched. Dyslipidemia occurred in 2.7% of patients who received 5 years of tamoxifen and was three times more common among those switched to the aromatase inhibitor.