Three years' follow-up from the ATAC trial is sufficient to change clinical practice: a debate.

Tamoxifen is currently the adjuvant treatment of choice for postmenopausal women with hormone-sensitive breast cancer. However, in the treatment of postmenopausal women with advanced disease, the third-generation aromatase inhibitor anastrozole ('Arimidex') has been shown to be at least as effective as tamoxifen, and to be more effective than tamoxifen in patients with estrogen receptor-positive disease. Furthermore, anastrozole is well tolerated and is associated with fewer adverse reactions (such as thromboembolic events, vaginal bleeding, and endometrial cancer) compared with tamoxifen. A change in clinical practice has now emerged for the first-line treatment of postmenopausal advanced disease in patients, with tamoxifen becoming the second- or third-line choice for many clinicians. These data have raised questions about the optimal adjuvant treatment for postmenopausal women with early breast cancer. The 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial has compared the efficacy and safety of tamoxifen and anastrozole in the adjuvant treatment of postmenopausal women with early breast cancer. At 3 years' follow-up in the overall population, anastrozole demonstrated a significant benefit compared with tamoxifen for disease-free survival (DFS) (89.4% vs. 87.4%; p = 0.013), time to recurrence (hazard ratio = 0.79; p = 0.008), and contralateral breast cancers (odds ratio = 0.42; 95% confidence interval: 0.22-0.79; p = 0.007). Anastrozole produced improvements in quality of life similar to tamoxifen and was better tolerated for a number of predefined adverse events. Of course, a large body of evidence is available regarding the safety profile of tamoxifen and some feel that more data are needed from the ATAC trial to demonstrate that the early advantages of anastrozole over tamoxifen can be maintained in the longer term. However, a follow-up analysis at 47 months has confirmed that the tolerability profile and the absolute benefit of anastrozole were maintained over the extended follow-up period, demonstrating that the benefits of anastrozole are likely to be maintained over the long term. This review assesses these and other data from the ATAC trial and presents the arguments for and against whether 3 years' follow-up is sufficient to inform a change in clinical practice for the adjuvant treatment of postmenopausal women with early breast cancer.