529 Background: BIG 1-98 is a randomized, phase III study that compares five years of tamoxifen (tam) or letrozole (let), (monotherapy arms), or their sequences (tam-let or let-tam) in post-menopausal women with ER+ early BC. In the monotherapy arms, the magnitude of benefit of adjuvant let compared with tam varies by histology (greater in invasive lobular carcinoma (ILC) than invasive ductal carcinoma (IDC)). In this analysis we investigate the magnitude of benefit of let compared to tam-let and let-tam according to histology (IDC and ILC) at 96 months of median follow-up. Methods: There were 4,634 patients enrolled in the let, tam-let and let-tam arms of BIG-98. This analysis includes patients with centrally-reviewed histological subtype (n=4,223); classified as classic ILC or IDC (n=3,790); and with centrally reviewed ER, PgR and Ki67 (n=3,212). Results: The 8-year DFS and OS univariate estimates (±SE) for IDC and ILC are presented in the Table. When correcting for classic clinicopathological variables, treatment assignment was not a significant predictor of DFS and OS. Conclusions: We observed a trend toward greater magnitude of benefit in favor of let monotherapy for ILC than IDC. In the ILC subset, improvements for both DFS and OS were seen for let when compared to tam-let or let-tam, though not statistically significant. This may be due to the reduced number of ILC patients across subgroups. The present analysis is consistent with previous data from the monotherapy arms where let was associated with better DFS and OS than tam for ILC, and suggests that let might be the preferred upfront regimen for patients diagnosed with ILC. Clinical trial information: NCT00004205. [Table: see text]