Personalized Predictions of Neoadjuvant Chemotherapy Response in Breast Cancer Using Machine Learning and Full-field Digital Mammography Radiomics

Ye Ruan ^1,2,3 Xingyuan Liu ^1,2,3 Yantong Jin ^1,2,3 Mingming zhao ^1,2,3 Xingda Zhang ^3,4,5 Xiaoying Cheng ^1,2,3 Yang Wang ^1,2,3 Siwei Cao ^1,2,3 Menglu Yan ^1,2,3 Jianing Cai ^1,2,3 Mengru Li ^1,2,3 BO GAO ^1,2,3*

• ¹ Departments of Radiology, Second Affiliated Hospital, Harbin Medical University, Harbin, China
• ² The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China
• ³ Harbin Medical University, Harbin, Heilongjiang, China
• ⁴ Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China
• ⁵ Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China

Objective: This study aimed to develop a comprehensive nomogram model by integrating clinical pathological and full-field digital mammography (FFDM) radiomic features to predict the efficacy of neoadjuvant chemotherapy (NAC) in breast cancer patients, thereby providing personalized treatment recommendations. Methods: A retrospective analysis was conducted on the clinical and imaging data of 227 breast cancer patients from 2016 to 2023 at the Second Affiliated Hospital of Harbin Medical University. The patients were divided into a training set (n=159) and a test set (n=68) with a 7:3 ratio. The region of interest (ROI) was manually segmented on FFDM images, and features were extracted and gradually selected. The rad-score was calculated for each patient. Five machine learning classifiers were used to build radiomics models, and the optimal model was selected. Univariate and multivariate regression analyses were performed to identify independent risk factors for predicting the efficacy of NAC in breast cancer patients. A nomogram prediction model was further developed by combining the independent risk factors and rad-score, and probability-basedrisk stratification was applied. An independent cohort was collected from an external hospital to evaluate the performance of the model.The radiomics model based on support vector machine (SVM) demonstrated the best predictive performance. FFDM tumor density and HER-2 status were identified as independent risk factors for achieving pathologic complete response (PCR) after NAC (P<0.05). The nomogram prediction model, developed by combining the independent risk factors and rad-score, outperformed other models, with areas under the curve (AUC) of 0.91 and 0.85 for the training and test sets, respectively. Based on the optimal cutoff points of 103.42 from the nomogram model, patients were classified into high-risk probability and low-risk probability groups. When the nomogram model was applied to an independent cohort of 18 47 patients, only one four patients was misclassified as achieving PCR after NAChad incorrect diagnoses. The nomogram model demonstrated stable and accurate predictive performance.The nomogram prediction model, developed by integrating clinical pathological and radiomic features, demonstrated significant performance in predicting the efficacy of NAC in breast cancer, providing valuable reference for clinical personalized prediction planning.