Abstract Background: Estrogen-receptor (ER)+ breast cancers have a favorable prognosis in the first several years after diagnosis, with adjuvant endocrine therapies for treatment. However, in later years, ER+ breast cancer is associated with poorer prognosis compared to ER- breast cancer. Predictors of late recurrence in women with ER+ breast cancer, and in particular lifestyle factors, have been little studied. Using data from a pooling project of breast cancer survivor cohorts (After Breast Cancer Pooling Project), we prospectively evaluated the association of post-diagnosis lifestyle factors and comorbidities with late breast cancer outcomes. Methods: Analyses included 6,129 women diagnosed with stage I-III invasive ER+ breast cancer (1990-2004) from three US prospective cohorts, who survived disease-free for five years. Pooled and harmonized data were available for post-diagnosis lifestyle factors, comorbidities, cancer treatment, tumor characteristics, and socio-demographics. Late outcomes (defined as >5 years post-diagnosis) included breast cancer recurrence, breast cancer specific-mortality (BCSM), and all-cause mortality. Lifestyle factors and comorbidities were assessed at a mean of about 2 years post-diagnosis. Study heterogeneity was evaluated by the Q statistic. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models stratified by study. Results: After a median follow-up of 6.9 years (11.9 years post-diagnosis), 645 deaths and 564 recurrences were documented. Five-year recurrence and all-cause mortality rates were 7.2% and 6.1%, respectively. Ten-year recurrence and all-causes mortality rates were 12.1% and 15.4%, respectively. In multivariable models, recreational physical activity (PA) of 10-MET h/wk was associated with reduced all-cause mortality (HR: 0.71, 95% CI: 0.60-0.84) and BCSM (HR: 0.77, 95% CI: 0.61-0.99), and non-significantly reduced recurrence risk (HR: 0.87, 95% CI: 0.73-1.03). Multivitamin and antioxidant vitamin supplement use were inversely associated with recurrence (HRs (95% CIs): 0.74 (0.62-0.87) and 0.75 (0.61-0.91), respectively). Current smoking was associated with increased risk of all-cause and BCSM ((HRs (95% CIs): 2.58 (1.99-3.35)) and 1.87 (1.22-2.88), respectively). Women with diabetes had increased risk of late outcomes (HRs 95% CIs: 1.35 (0.95-1.92) for recurrence, 1.86 (1.45-2.40) for all-cause mortality, and 1.75 (1.12-2.73) for BCSM. Hypertension was significantly associated with all-cause mortality only (HR: 1.42, 95% CI: 1.19-1.70). Obesity (BMI ≥30 kg/m2) was not associated with late outcomes. Conclusion: In this large study, post-diagnosis lifestyle factors were important predictors of late breast cancer outcomes. Our findings suggest PA and multivitamin use may improve long-term prognosis for ER-positive breast cancer. Citation Format: Sarah J. Nechuta, Wendy Y. Chen, Marilyn L. Kwan, Elizabeth M. Poole, Shirley W. Flatt, John P. Pierce, Bette J. Caan, Xiao Ou Shu. Lifestyle factors are associated with late breast cancer outcomes among 5-year survivors of estrogen-receptor positive breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2182. doi:10.1158/1538-7445.AM2014-2182