Background: Adjuvant endocrine therapy (AET) reduces recurrence and mortality in women with hormone receptor-positive (HR+) breast cancer (BC). Sexual problems are common during AET but are under-reported and under-treated in routine clinical care. Patient reported outcomes (PRO) improve clinician awareness of patient symptoms. We present an analysis of prospectively collected PRO from a clinic-based registry of women with HR+ BC receiving AET with the aim of identifying factors associated with developing or worsening sexual problems. Methods: Women with stage 0-III BC initiating AET were enrolled in a prospective clinic-based registry Mar 2012-Dec 2016. Participants completed PRO surveys at baseline (BL) and 3, 6, 12, 24, 36, 48 and 60 months (mo). Sexual problems were evaluated by the MOS Sexual Problems (MOS-SP) measure (range 0-100; higher scores indicate more sexual problems). Respondents rate severity of problems in 4 domains of sexual function on a 4-point scale (“not a problem”, “a little of a problem”, “somewhat of a problem” and “very much a problem”). We considered participants who responded “somewhat of a problem” or “very much a problem” for ≥1 domain to have a sexual problem at that time point. Based on the empirical rule effect size method, we defined clinically significant developing or worsening sexual problems during AET as an increase in MOS-SP score by ≥8 from BL. Women with MOS-SP score >92 at BL were excluded. Other PRO surveys were the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES) scale and NIH PROMIS measures for pain interference, fatigue, depression, anxiety, physical function (PF) and sleep disturbance. We evaluated associations between worsening of PROMIS T-scores in 4-point increments and FACT-ES score in 5-point increments with change in the MOS-SP score by ≥8. Additional covariates were clinical and demographic factors including socioeconomic status (SES). We used neighborhood poverty (NP) rate >15% as a surrogate for low SES based on US census estimates of the % of persons in a zip code below the federal poverty line. We performed logistic regression with generalized estimating equations to account for repeated observations. The final multivariable model was determined with a forward stepwise selection algorithm. Results: Among 300 participants, 195 (65%) were post-menopausal, 252 (84%) white and 30 (10%) black, 134 (45%) on tamoxifen and 166 (55%) on an aromatase inhibitor. Stage distribution was 0: 28 (9%); I: 180 (60%); II-III: 92 (31%). Prior to ET, 132 (44%) had mastectomy, 84 (28%) had chemotherapy and 199 (66%) had radiation (RT). 40 (13%) were of low SES. Median follow-up is 56 mo. 165 (55%) participants reported ≥1 sexual problem during participation. At BL, median MOS-SP score was 8.32 (range 0-92). There was no significant change in mean MOS-SP score from BL to 48 mo (p=0.74). In univariate analyses, worsening scores on all PRO measures were associated with increase in MOS-SP score by ≥8, however on multivariate analysis, only worsening endocrine symptoms (OR 1.34, 95% CI 1.21-1.48, pConclusions: Women receiving AET at risk for developing or worsening sexual problems include those with worsening endocrine symptoms and worsening PF plus those who have undergone mastectomy or RT. Routine assessment for sexual problems in this population may reduce under-detection and identify women who can benefit from interventions to improve sexual function. Citation Format: Neha Verma, Amanda L. Blackford, David Lim, Elissa Thorner, Jennifer Lehman, Claire Snyder, Caroline A. Snyder, Vered Stearns, Karen L. Smith. Factors associated with sexual problems during adjuvant endocrine therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-58.