12076 Background: Weight gain is common after a breast cancer diagnosis. The incidence of and risk factors for weight gain during adjuvant endocrine therapy (ET) are poorly described. Limited data support an association between emergent symptoms and weight gain after a breast cancer diagnosis. Methods: We enrolled women with stage 0-III breast cancer initiating ET in a prospective clinic-based cohort. We assessed symptoms with the FACT-ES and PROMIS pain interference, depression, anxiety, fatigue, sleep disturbance and physical function measures at baseline (BL), 3, 6, 12, 24, 36, 48 and 60 months (mo). We defined emergent symptoms at 3 and/or 6 mo as worsening of 4 points from BL on PROMIS measures and 5 points from BL on the FACT-ES. We abstracted weight and menopausal status from charts. The primary outcome of this secondary analysis was weight gain (dichotomized as ≥5% vs < 5% of body weight compared to BL) through 60 mo. We evaluated the association between weight gain during ET and menopausal status. We also evaluated the associations between clinicodemographic factors and emergent symptoms with weight gain and if these associations differed by menopausal status. We performed logistic regression modeling with GEE to account for the longitudinal design. We identified a multivariable model for the set of factors associated with weight gain among pre-menopausal women taking ET. Results: 309 of 321 participants with BL and ≥1 follow-up (FU) weight were included. 263 (85%) had stage I-II disease, 99 (32%) were pre-menopausal, 259 (84%) were White and 32 (10%) were Black. Prior to ET, 45% had mastectomy, 66% had radiation, and 28% received chemotherapy. 4% of pre- and 82% of post-menopausal participants initiated an aromatase inhibitor (AI); all others initiated tamoxifen (Tam). 17% of pre-menopausal participants received ovarian suppression. At BL, 75% of Black and 59% of White participants were overweight/obese. With a median FU of 56 mo, 51% of pre- and 34% of post-menopausal participants gained ≥5% body weight (OR 1.09, 95% CI 1.07-1.13, p < 0.001). For each PRO measure, > 20% of participants had emergent symptoms. Worsening of physical function and pain interference scores at 3 and/or 6 mo were differentially associated with weight gain according to menopausal status (interaction p-values ≤0.05). On multivariate analysis, factors associated with weight gain among pre-menopausal participants were ET (AI vs Tam) (OR 2.8, 95% CI 0.90- 8.77, p = 0.08), prior mastectomy (OR 2.06, 95% CI 0.89-4.77, p = 0.09), emergent pain interference (OR 2.49, 95% CI 0.99-6.24, p = 0.05) and race (White vs other) (OR 7.13, 95% CI 1.29-39.4], p = 0.02). Conclusions: Weight gain during ET for breast cancer is more frequent among pre-menopausal than post-menopausal women. Worsening pain soon after ET initiation, receipt of AI, prior mastectomy and race may identify pre-menopausal women at risk for weight gain for whom prevention strategies are a priority.