Abstract Background: The decision-making process regarding breast cancer treatment options, specifically breast conserving surgery (BCS) versus mastectomy, is a complex and sensitive matter that takes into account the patient's preferences and their eligibility for BCS. A range of anatomical factors, such as tumor size, breast size, and proximity of the tumor to the skin, can influence the surgeon's recommendation regarding BCS or mastectomy. While mastectomy may be the only viable option for patients with large tumors, those with smaller tumors often have the opportunity to collaboratively decide with their surgeon on the most appropriate approach to ensure oncologic success and minimize potential cosmetic deformity. To facilitate this decision-making process, we developed a tool capable of providing informed recommendations on BCS or mastectomy based on standard of care imaging patient data. By integrating these recommendation capabilities, we aim to enhance the decision-making process and improve patient outcomes in breast cancer treatment. Methods: To assist surgeons and patients in determining a patient’s eligibility for breast conserving surgery (BCS), we developed the BCS Feasibility Score. The BCS Feasibility Score is generated from a binary classifier machine learning model and is representative of the probability that a given patient could receive BCS. The score is based solely on the output from TumorSight Viz, a software platform that uses only pre-treatment T1-weighted DCE MRI and applies a suite of deep learning algorithms to segment the patient’s disease and the surrounding breast tissues. From the multi-tissue segmentation generated using TumorSight Viz, we extracted 25 spatial morphology features to use in the model development process. The training and testing sets were a subsample of a publicly available dataset (Saha, et al, 2018). We selected patients that received either BCS or mastectomy and had a viable T1-weighted DCE MRI. Bi-lateral cases were excluded. The total training/testing set consisted of n = 749 cases, 363 of which received mastectomy and 386 who received BCS. Before model training occurred, we split 20% of the sample to use as the test set. We then trained a random forest classifier across a range of pre-set hyper-parameters, using a total of 25 features as inputs, and using 5x cross-validation in the training set. We then assessed model performance in the testing set only. Results: In the test set, 76 cases received BCS versus 74 that received mastectomy. We successfully predicted BCS in 56 out of 76 cases (74%), and mastectomy in 46 out of 74 cases (62%). Overall, we observed an AUC = 0.76 and an F1 score = 0.66, indicating moderate to strong model performance. The most important features in the model, as measured by SHAP values, included the axis aligned tumor longest dimension (mm), the closest distance between the tumor and the nipple (mm), the volume of the tumor convex hull (mL; dilated uni-centrically), and the ratio of tumor convex hull volume to breast volume. We tested the model’s performance in a fully independent holdout validation set of 579 cases. Within this validation set, 335 patients received BCS versus 244 received mastectomy. We successfully predicted BCS in 254 out of 335 cases (76%), and mastectomy in 149 out of 244 cases (61%). Overall, we observed an AUC = 0.75 and an F1 score = 0.63. Validation set performance mirrored results observed in the test set, indicating strong generalizability. In the validation set, comparing patients who underwent BCS to those who underwent mastectomy, we observed significant differences across all four of the most predictive features. Conclusion: TumorSight Viz and the BCS Feasibility Score help empower both patients and clinicians with information and tools to facilitate surgical planning decisions. Citation Format: John Pfeiffer, Bradley Feiger, Anuja Antony, Joseph Peterson. Predicting the feasibility of breast conserving surgery using pre-treatment standard of care DCE-MRI: a novel clinical decision support tool for breast cancer surgical planning [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-02-10.