Breast cancer continues to be the most commonly occurring non-skin cancer in women. Survivorship is of increased importance as women are living longer after treatment. Cardiac toxicity after radiotherapy (RT) is a concern for such patients who otherwise have excellent life expectancy. We hypothesize via this exploratory analysis that dose-weighted texture features from pre-treatment CT may predict for cardiac toxicity post-RT for women with breast cancer. We retrospectively analyzed 17 patients treated with standard RT for localized breast cancer between 2011-2016 at a single institution. Patients had no known heart disease pre-RT. Eight patients with cardiac disease post-RT, diagnosed via echocardiogram or cardiac catheterization, were compared to 9 patients without cardiac disease post-RT. Using published contouring guidelines, each treatment planning CT was used for delineation of the heart, cardiac chambers, left main coronary artery, left anterior descending coronary artery, left circumflex artery (LCX), right coronary artery, atrioventricular (AV) node, ascending aorta and pulmonary artery. Ninety-two geometric, first-, second-, and third-order conventional texture features were extracted for each structure. An in-house developed software modified the features by dose weighting on a voxel-by-voxel basis, resulting in an additional 65 dose-weighted textures. Random forest was used for analyses. A univariate logistic regression model was used to estimate odds ratio (OR) and p-value for each imaging feature – with and without dose weighting. Eight patients were diagnosed with pericarditis (n = 1), arrhythmia (n = 1), coronary artery disease (n = 2), or heart failure (n = 4) a median of 3 years after completion of RT (mean: 3.5 years). RT was delivered to the left breast (n = 4), left chest wall (CW, n = 2), and right CW (n = 2) with mean heart dose of 2.1 Gy (range: 0.4-5.25 Gy). The 9 reference patients without cardiac sequelae were treated with RT to the left chest wall with mean heart dose of 2.7 Gy (range: 1.4-6.8 Gy). On univariate analysis, left atrium volume (OR: 39.89, p = 0.04) and a dose-weighted feature of the right ventricle (OR: 0.15, p = 0.03) were significantly associated with cardiac disease. Several dose-weighted texture features approached significance including those of the AV node (OR: 42.37, p = 0.08), left atrium (OR 0.10, p = 0.07), LCX (OR:8.5, p 0.09), and right atrium (OR:8.5, p = 0.09). Area under the receiver operating characteristic curve (AUC) ranged between 0.75 and 0.88. Dose-weighted texture features of the right ventricle and left atrium volume were significantly associated with development of cardiac disease post-RT. Multiple dose-weighted features approached significance, suggesting that distribution of dose amongst subsites may affect cardiac outcomes. Future directions include expansion of the database by cardiac disease type with covariate analysis including systemic therapy and comorbidities.