San Antonio Breast Cancer Symposium 2007—Adjuvant endocrine therapy update: ATAC 100 highlights

The two main classes of adjuvant hormonal therapy used in the treatment of postmenopausal women with hormone receptor–positive breast cancer are selective estrogen receptor modulators (for example , tamoxifen) and the aromatase inhibitors (AIs—for example, anastrozole, letrozole, exemestane). The " gold standard " of 5 years of ad-juvant tamoxifen has clearly been challenged (and some would argue surpassed) by the accumulating evidence from the adjuvant AI trials. In addition to a tolerable side-effect profile, the AI treatment strategies (upfront, switch, or extended adjuvant) have all demonstrated improved disease-free survival over adjuvant tamoxifen. They also offer a reduced incidence of thromboembolic disease and endome-trial pathology, but come at the price of increased musculoskeletal symptoms, osteopenia and os-teoporosis, and an associated increased fracture rate. Follow-up data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial were just presented at the 2007 San Antonio Breast Cancer Symposium (SABCS) and have recently been published 1. With a median follow-up of 100 months, ATAC is the longest-running AI trial to date, and its data continue to demonstrate improved efficacy for 5 years of upfront anastrozole over tamoxifen alone. As was seen in the last ATAC update and in the tamoxifen overview data, the absolute difference in time to recurrence (TTR) continues to increase even after hormonal treatment is stopped at 5 years—the " carryover effect " : • At 5 years: 2.8% TTR (anastrozole 9.7% vs. tamoxifen 12.5%) • At 9 years: 4.8% TTR (anastrozole 17.0% vs. tamoxifen 21.8%) • Recurrence rates remained lower on anastrozole as compared with tamoxifen after treatment completion [hazard ratio (HR): 0.75; 95% confidence interval: 0.61 to 0.94; p = 0.01] Although a nonsignificant numeric excess of non-breast cancer deaths in patients without a breast cancer recurrence was noted in the anastrozole group, no difference in overall survival was observed (HR: 0.97; p = 0.7). No unexpected toxicity data were reported, and after the intended duration of endocrine therapy had been completed, no " carryover " with respect to increased fracture incidence was seen. Patients actively receiving anastrozole over tamoxifen had a higher annual fracture rate (2.93% vs. 1.90% respectively ; incidence rate ratio: 1.55; p < 0.0001), but no difference was observed in those rates after endocrine therapy was complete (1.56% vs. 1.51% respectively; incidence rate ratio: 1.03; p = 0.79). Bisphosphonate use overall—let alone prophy-laxis—was low in the trial. The hope is that pre-emptive measures to identify …