Background: Four cycles of chemotherapy are frequently used as standard adjuvant chemotherapy for patients with low-risk primary breast cancer, though other regimens such as CAF, CMF, and TAC frequently are given for 6 cycles. Using a phase 3 factorial design we attempted to define whether 6 cycles of one chemotherapy regimen are superior to 4 cycles in patients with low-risk primary breast cancer. We also sought to determine if T would be equally efficacious as compared to AC, with reduced toxicity. Methods: The study enrolled women with operable breast cancer and 0-3 positive nodes. Study stratifiers were ER/PgR, HER2, and menopausal status. When the study was activated in May 2002, AC (60 and 600 mg/m2) was administered every 3 wks for 4 or 6 cycles, and T (80mg/m2) weekly for 12 or 18 wks. In 2003 (after 570 enrolled patients) treatment schedule was changed to every 2 wks for both AC and T (175 mg/m2), each given for 4 or 6 cycles. In 2008 accrual to the 6-cycle regimens was permanently closed due to slow accrual, with 3173 patients enrolled. The primary endpoint for this comparison was the superiority of 6 vs 4 cycles in relapse-free survival (RFS). The study was powered to have 567 RFS events. Data comparing AC with T are not yet available. Results: This report describes the impact of treatment duration and includes the 3173 patients randomized to 6- versus 4-cycles of chemotherapy, 93% of whom had node-negative disease. At a median follow-up of 4.6 years (2.5 - 8 yrs), the number of RFS events is 288 (with 138 on 4 cycles vs 150 on 6 cycles). The 4-yr RFS was 91.6% and 91.8% for 6 and 4 cycles, respectively. The Hazard Ratio of 6 to 4 cycles was 1.10 (95% CI = 0.87-1.39, p=0.42). Four-year OS was 95.3% and 96.4% for 6 and 4 cycles, respectively, with a HR of 6 to 4 cycles of 1.31 (95% CI = 0.95-1.82, p=0.097). Based on the present data the Bayesian predictive probability of concluding superiority of 6 cycles [a primary goal of the study] with 567 RFS events is only 0.001. There was no interaction between the number of cycles and type of chemotherapy, ER/PgR status, or HER2 status. In particular, the effect of number of cycles on RFS and OS was similar for both AC and T.

Conclusions: For women with primary breast cancer and 0-3 positive nodes, we found no evidence that extending chemotherapy from 4 to 6 cycles improves clinical outcome.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S6-3.