crossed over to Let after the presentation of these results. The three Letcontaining treatments remained blinded. New results include the evaluation of Let and Tam given in sequence compared with Let alone and an update the comparison of Let and Tam monotherapy. Methods: 6182 patients were randomized to the 4-arm option (entry Sep99–May03) [Tam × 5 years (Tam), Let × 5 (Let), Tam × 2→ Let × 3 (Tam→ Let), or Let × 2→Tam × 3 (Let→Tam)]. Another 1828 patients were randomized to the 2-arm option (Tam vs. Let; entry Mar98–Mar00). The primary endpoint was DFS (time from randomization to first occurrence of invasive breast cancer recurrence, invasive contralateral breast cancer, second non-breast malignancy, or death from any cause). The update will focus on the clinically-relevant comparisons evaluating Tam→ Let vs. Let and Let→Tam vs. Let, and Let vs. Tam. Results: The protocol-specified update of the comparison of Let × 5 vs. Tam × 5 (i.e., the monotherapy arms, including patients in both the 2-arm and 4-arm options; N=4922) suggests improved overall survival for patients treated with Let (HR=0.87, 95CI: 0.75−1.02, p = 0.08, 76 months median follow-up). In this comparison, about a quarter of the patients in the Tam arm selectively crossed over to Let after 3−5 years of Tam. For the sequential treatment analysis (71 months median follow-up), hazard ratios comparing treatments from time of initial randomization in terms of DFS, overall survival, and time to distant recurrence are displayed in the figures.