Update on ATAC.

The third-generation aromatase inhibitors (AIs) have improved efficacy and safety versus tamoxifen for treatment of advanced breast cancer. Currently, anastrozole is the only third-generation AI with adjuvant therapy data in postmenopausal women. Initial and updated results from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial (median follow-up, 47 months) confirm it to be more effective than tamoxifen for disease-free survival with several important tolerability benefits. As a result, there has been much debate about whether or not anastrozole should be used routinely to treat postmenopausal women with early breast cancer. In its review, the American Society of Clinical Oncology Health Services Research Committee agreed that the updated ATAC analyses provided a greater level of assurance, in terms of both toxicity and efficacy, for use of anastrozole in the adjuvant setting. However, pending 5-year data from ATAC and other trials of adjuvant AI use, adjuvant anastrozole was recommended by American Society of Clinical Oncology Health Research Committee for use only under certain circumstances, with 5 years of tamoxifen remaining the standard. Anastrozole should be the preferred AI in this setting; data from the ATAC trial should not be extrapolated to other members of the class. Despite this conservative recommendation, the overall risk:benefit profile from the ATAC trial favors anastrozole, and it is expected that a more favorable efficacy and adverse effect profile will be maintained. Anastrozole should, therefore, now be considered a valid alternative option to tamoxifen for adjuvant hormonal treatment in all postmenopausal women with hormone receptor-positive early breast cancer.

Anastrozole↗

PubMed2004

Prevention strategies with aromatase inhibitors.

Aromatase (estrogen synthetase) inhibitors are superior to tamoxifen in terms of both efficacy and toxicity in the treatment of advanced breast cancer and also in the neoadjuvant setting. Recent results from the Arimidex, Tamoxifen, Alone or in Combination adjuvant trial showed a marked reduction in contralateral primary breast cancer with anastrozole, an apparent prevention effect. A similar effect was seen in the MA.17 adjuvant trial comparing letrozole with placebo after 5 years of adjuvant tamoxifen. This has accelerated interest in aromatase inhibitors as primary preventive therapy. Two studies being conducted by the National Cancer Institute of Canada's Clinical Trials Group select women by virtue of mammographic breast density. The International Breast Cancer Intervention Study 2 trial randomizes women at elevated risk to anastrozole or placebo. Because of its steroidal structure, exemestane may be more effective than the nonsteroidal aromatase inhibitors and may protect bone and lipid metabolism from the effects of estrogen ablation. Elevated prostaglandin E2 levels from cyclooxygenase-2 induction by preinvasive and invasive breast lesions increase a number of tumor-promoting pathways, including aromatase, as well as angiogenetic, antiapoptotic, and others. Additive or synergistic effects between celecoxib, a cyclooxygenase-2 inhibitor, and exemestane have been demonstrated and have led to the National Cancer Institute of Canada's Clinical Trials Group MAP.3 trial, which will randomize women at elevated risk to placebo or to exemestane with or without celecoxib. The efficacy and long-term toxicity data from the aromatase inhibitor prevention trials, and the identification of risk profiles from trial results, are awaited with interest.

Anastrozole↗