Establishment and external validation of a prognostic model for predicting disease-free survival and risk stratification in breast cancer patients treated with neoadjuvant chemotherapy

Jianguo Lai,1,2 Hongli Wang,1,2 Jingwen Peng,3 Peixian Chen,4 Zihao Pan1,2 1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 3Department of Rehabilitation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 4Department of Breast surgery, The First People’s Hospital of Foshan, Foshan, People’s Republic of China Background: The eighth edition of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for survival prediction and risk stratification in breast cancer (BC) patients after neoadjuvant chemotherapy (NCT) is of limited efficacy. This study aimed to establish a novel prognostic nomogram for predicting disease-free survival (DFS) in BC patients after NCT. Patients and methods: A total of 567 BC patients treated with NCT, from two independent centers, were included in this study. Cox proportional-hazards regression (CPHR) analysis was conducted to identify the independent prognostic factors for DFS, in order to develop a model. Subsequently, the discrimination and calibration ability of the prognostic model were assessed in terms of its concordance index (C-index), risk group stratification, and calibration curve. The performance of the nomogram was compared with that of the eighth edition of the AJCC TNM staging system via C-index. Results: Based on the CPHR model, eight prognostic predictors were screened and entered into the nomogram. The prognostic model showed better performance (p<0.01) in terms of DFS prediction (C-index: 0.738; 95% CI: 0.698–0.779) than the eighth edition of the AJCC TNM staging system (C-index: 0.644; 95% CI: 0.604–0.684). Stratification into three risk groups highlighted significant differences between the survival curves in the training cohort and those in the validation cohort. The calibration curves for likelihood of 3- and 5-year DFS indicated optimal agreement between nomogram predictions and actual observations. Conclusion: We constructed and externally validated a novel nomogram scoring system for individualized DFS estimation in BC patients treated with NCT. This user-friendly predictive tool may help oncologists to make optimal clinical decisions. Keywords: breast cancer, neoadjuvant chemotherapy, disease-free survival, nomogram, prognosi