THE BREAST, VOLUME 14, SUPPLEMENT 1, FEBRUARY 2005

Updated Abstract

I P ~ Efficacy data from the ATAC ("Arimidex", Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment

Tony Howell, on behalf of the ATAC Trialists' Group. Christie Hospital, Manchester, UK

The ATAC trial compared the efficacy of anastrozole and tamoxifen in the primary adju- vant treatment of postmenopausal women (n=9366) with operable, early-stage breast cancer (EBC). The primary efficacy endpoint disease-free survival (DFS) and sec- ondary endpoints including time to recurrence (TTR), incidence of new contralateral breast cancer (CLBC), time to distant recurrence (TTDR), overall survival (OS) and breast cancer death were evaluated in both the intent-to-treat population (ITT) and the hormone receptor-positive (HR+ve) population (84% of ITT).

After a median follow-up of 68 months, there were significant improvements in DFS (hazard ratio [HR] 0.87; 95% confidence interval [CI] 0.78, 0.97; p=0.01), TTR (HR 0.79; 95% CI 0.70, 0.90; p=0.0005) and CLBC (HR 0.58; 95% CI 0.38, 0.88; p=0.01) in the anastrozole group compared with tamoxifen. The DFS (HR 0.83; 95% CI 0.73, 0.94; p=0.005), TTR (HR 0.74; 95% CI 0.64, 0.87; p=0.0002) and CLBC advantages of anastrozole over tamoxifen were even more apparent in the HR+ve population. In addition, anastrozole treatment resulted in a 49% reduction in invasive CLBC in the ITT population (95% CI 19-68%; p=0.004) and a 57% reduction in the HR+ve population (95% CI 29-75%; p=0.001).

Absolute differences continued to grow over time with continued divergence of the DFS and TTR curves even after treatment completion. The characteristic peak of re- currence with tamoxifen during the first 3 years of treatment was not apparent with anastrozole and benefits were seen throughout the entire follow-up period.

There was a significant benefit in TTDR for anastrozole over tamoxifen (HR 0.86; 95% CI 0.74, 0.99; p=0.04). OS was similar for anastrozole and tamoxifen (HR 0.97; 95% CI 0.85, 1.12; p=0.7) but there was a 12% reduction in breast cancer deaths in the anastrozole group, which did not reach statistical significance (HR 0.88; 95% CI 0.74, 1.05; p=0.2). Similar trends were observed in the HR+ve population.

These results clearly demonstrate the superior efficacy of anastrozole over tamox- ifen, which extends beyond completion of trial therapy and continues to increase over time. This "carry-over" effect appears to be more evident in the anastrozole group. In addition, significant benefits in DFS and TTR demonstrated by anastrozole over ta- moxifen have now translated into a benefit in TTDR. Five years of anastrozole should now be considered as the standard of care for postmenopausal women with hormone- sensitive EBC.