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Objective: Patient-reported toxicities after breast radiotherapy merit understanding in order to inform decisions and target supportive care interventions. Methods: As part of a collaborative quality improvement initiative, the Michigan Radiation Oncology Quality Consortium prospectively collects patient-reported outcomes data from women treated for breast cancer at 26 practices across the state. Of all 11,107 patients treated with lumpectomy and whole breast radiation therapy between 1/1/2012 and 12/31/2018, 2817 refused patient surveys. We describe here the maximal toxicity reported by the 7689 patients who provided survey responses within 7 days of end of treatment and for whom we had sufficient data to determine dose-fractionation and treatment fields. Multivariable logistic regression models separately identified the individual and treatment characteristics associated with 1) breast pain, 2) a bother scale (related to itching, stinging/burning, swelling, or hurting of the treated breast), and 3) fatigue. Breast pain was considered moderate or severe when score ≥4 on modified 10-point Brief Pain Inventory measure. Bother from multiple breast symptoms was considered frequent when score ≥3 on a scaled measure (range 0-4) averaging responses on four items derived from the Skindex. Fatigue was considered severe when rated as present “always” or “most of the time” over past four weeks. Results: Moderate or severe breast pain was reported by 2882 (37.5%) overall: 1022 (28.3%) of those receiving hypofractionation (HF) and 1860 (45.7%) of those receiving conventional fractionation (CF). Frequent bother from multiple breast symptoms was reported by 1029 (13.4%) overall: 288 (8.0%) after HF and 741 (18.2%) after CF. Severe fatigue was reported by 1795 (23.4%) overall: 681 (18.8%) after HF and 1114 (27.4%) after CF. In addition to treatment fractionation (p Conclusions: In this large observational dataset of patient-reported toxicities after whole breast radiotherapy, substantial differences existed by radiotherapy dose-fractionation. Race differences in breast pain and bother existed despite controlling for multiple other factors, including age, body habitus, comorbidities, and treatment characteristics; further research is needed to understand what drives these differences in order to target potentially modifiable factors. Intensification of supportive care may be appropriate for subgroups identified as being vulnerable to greater toxicity. Multivariable Models of Patient-Reported Toxicity OutcomesIndependent VariableOdds Ratio (CI) [p value] in Model with Dependent Variable=Moderate or Severe Breast PainOdds Ratio (CI) [p value] in Model with Dependent Variable=Frequent Bother from Multiple Breast SymptomsOdds Ratio (CI) [p value] in Model with Dependent Variable=Severe FatigueAge 70+ vs 60-690.77 (0.67 - 0.89) [p40 vs Overweight 25- Citation Format: Reshma Jagsi, Kent Griffith, Frank Vicini, Jay Burmeister, Michael Dominello, Inga Grills, James Hayman, Jean Moran, Peter Paximadis, Jeffrey Radawski, Eleanor Walker, Lori Pierce. Identifying patients at higher risk of toxicity after breast radiotherapy: Analysis of patient-reported outcomes in the Michigan Radiation Oncology Quality Consortium cohort [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD6-6.