Anastrozole Update: Superior Clinical Efficacy 

Abstract & Commentary

Synopsis: An update from the ATAC trial at a median follow-up of 47 months (approximately 14 months later than the initial report from the trial) continues to demonstrate increased efficacy for anastrozole when compared with tamoxifen for the treatment of early breast cancer in postmenopausal women. Parameters included disease-free survival, time to recurrence, and incidence of cancer in the contralateral breast. The toxicity data also are favorable, with less hot flashes, vaginal bleeding, and fewer cases of endometrial cancer, thromboembolic events, and cerebrovascular accidents. However, there were more fractures and other musculoskeletal adverse events observed in the women treated with anastrozole. Although the data are very encouraging, a longer follow-up period is likely to be required before this drug will supplant tamoxifen as the treatment of choice in this clinical setting.

Source: ATAC Trialists’ Group.Cancer. 2003;98:1802-1810.

The arimidex, tamoxifen alone or in combination (ATAC) trial is a large-scale, international, industry-sponsored interventional, randomized study involving almost 10,000 early-stage postmenopausal breast cancer patients who were randomized to receive either anastrozole alone or in combination with tamoxifen, or tamoxifen alone. A comprehensive report in 2002 described the findings at a median follow-up of 33 months1 and the current report updates the study, now with a median follow-up of 47 months. In the first report, it was apparent that anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC).

DFS estimates at 4 years remained significantly more favorable (86.9% vs 84.5%, respectively) for patients receiving anastrozole compared with those receiving tamoxifen (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.76-0.99; P = .03). The benefit generated by anastrozole in terms of DFS was even greater in patients with hormone receptor positive tumors (HR, 0.82; 95% CI, 0.70-0.96; P = .014). The hazard ratio for time to recurrence also indicated a significant benefit for patients receiving anastrozole (HR, 0.83; 95% CI, 0.71-0.96; P = .015), with additional benefit for patients with hormone receptor-positive tumors (HR, 0.78; 95% CI, 0.65-0.93; P = .007). Contralateral breast cancer incidence also occurred less frequently in the anastrozole-treated patients (odds ratio [OR], 0.56; 95% CI, 0.32-0.98; P = .042).

The updated safety analysis, performed 7 months after the first analysis (median duration of treatment, 36.9 months), also confirmed the earlier findings. Endometrial cancer, vaginal bleeding and discharge, cerebrovascular events, venous thromboembolic events, and hot flashes all occurred significantly less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures continued to occur significantly less frequently in the tamoxifen group.

Comment by William B. Ershler, MD

This update brings us one step further in establishing a more favorable profile for anastrozole in the treatment and/or prevention of hormone receptor-positive breast cancer. The question is whether the data are sufficient to establish anastrazole as the standard of care. For this, it will probably take additional time. Although it is likely the differences observed, when compared to tamoxifen, will indicate greater efficacy (longer overall survival), inasmuch as the surrogate markers of recurrence rate and time to recurrence usually are excellent predictors of overall efficacy. Nonetheless, the study is not mature enough to conclude that the safety profile will remain stable. The safety data presented represent a median treatment time of less than 3 years. It will be recalled that it took much longer than this to recognize the association of tamoxifen with endometrial cancer. Accordingly, before becoming established as the standard approach, a look beyond 5 years of treatment will be necessary. In the meantime, the gratifying result of observing 70% fewer contralateral breast cancers has prompted the examination of anastrozole in a large cancer prevention study in the United Kingdom. The second international breast cancer intervention study (IBIS II) will involve 6000 postmenopausal women who are not taking hormone replacement therapy and are at increased risk of breast cancer because they have one or more close relatives with the disease. Cognition and bone density will be carefully monitored in that trial.

Dr. Ershler, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC.


1. ATAC Trialists’ Group. Lancet. 2002;359:2131-3139.