Purpose: Epidemiologic and clinical evidence have shown an association between obesity and increased risk for breast cancer (BC) incidence and mortality. Data from human and animal studies support a potential role for weight loss in counteracting tumor-promoting properties of obesity in BC. However, dietary intervention clinical trials often show low patient adherence, especially among African American (AA) women compared to Caucasian (CC) women. They also show that AA women are disproportionately obese and lose less weight during behavior lifestyle interventions compared to CC with similar risk factors. We evaluated the efficacy and feasibility of a 10-week caloric restricted diet in patients undergoing radiation and have performed analysis to determine if adherence to dietary alterations is feasible in underrepresented patients. Methods: In an IRB approved clinical trial, we determined the feasibility and toxicity of dietary intervention during radiation in breast cancer patients 18 years and older who were undergoing breast conservation therapy with T1-2N0 cancers. The dietary intervention consisted of caloric intake reduction of 25% from baseline for a total of 10 weeks during their six-week radiation treatment which was administered to the whole breast to a dose of 50Gy with a 10Gy boost to the tumor bed. To optimize adherence to caloric restriction (CR), patients received personalized counseling, maintained food diaries, and were educated on behavioral modifications at weekly visits. To characterize the effects of CR, baseline physiologic and blood parameters were collected and compared with post intervention measurements and samples. Biometric and biological data collected during the study comparing compliant participants before and after the CaReFOR intervention was stratified by race and analyzed via two-sample paired t-test. The difference between AA and CC study participants was determined to be significant if the calculated p-value was less than < 0.05 (CI 95%). Results: A total of 32 female patients were enrolled in the CaReFOR trial, 16 were AA and 16 were CC. Participant demographics were similar across age, primary tumor size (pT), nuclear grade, and hormone receptor status. Evaluation of patients’ baseline diet demonstrated similar macronutrients across races, with AA showing less fruit/vegetable and grains. AA patients were more overweight compared to their CC counterparts. They also showed a more inflamed state compared to CC patients. The baseline inflammatory biomarker levels for ESR and cholesterol were significantly higher while adiponectin was significantly lower in AA than that of CC patients. The trends for insulin, HbA1c, and leptin were also higher for AA compared to CC. Following the 10-week diet, AA patients (87.3%) were more compliant than CC’s (81.3%). Both AA and CC patients lost weight during the trial, with AA having a significant loss in body fat and gain in muscle mass compared to CC. Similarly, after completing the CR diet, biological inflammatory markers improved in AA and CC patients. Particularly, in AA, there was a significant decrease in cholesterol levels, while insulin, leptin, and ESR serum levels trended downwards, suggesting a decreased inflammatory state. Conclusions: Contrary to published studies, we found AA patients are successful in adhering to dietary alterations and have a benefit with respect to physiologic and biologic parameters. Our dietary intervention was able to positively affect our AA patients adverse baseline factors such as obesity and inflammation. Future studies should consider dietary alterations as a possible means to decrease AA patient disparate outcomes in breast cancer. Citation Format: Siani Harding, Adeseye Adekeye, Edith P. Mitchell, Nicole Simone. Caloric Restriction for Oncology Research (CaReFOR): Assessing dietary adherence and outcomes in African American patients during breast cancer treatment. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-52.