Abstract
BACKGROUND: Breast cancer (BC) in women of reproductive age (<45 years) is characterized by aggressive biology and elevated recurrence risk despite curative breast-conserving surgery (BCS) and radiotherapy. Current staging systems inadequately predict outcomes in this population, necessitating precision tools to guide therapy. This study aims to develop validated nomograms integrating clinicopathologic variables to improve survival prediction and therapeutic personalization for young operable BC patients. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016), we analyzed 9,477 women aged 20-45 years with operable BC (T1-3N0-1M0) treated with BCS and radiotherapy. Prognostic factors for overall survival (OS) and cancer-specific survival (CSS) were identified via Cox regression. Nomograms integrating clinicopathologic variables were developed (training cohort: n=6,633) and validated (test cohort: n=2,844) using C-index, time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis. Chemotherapy benefits were assessed across different risk subgroups. RESULTS: Tumor grade [poorly differentiated: hazard ratio (HR) =4.46 for OS; HR =6.01 for CSS], lymph node metastasis (N1: HR =1.96 for OS; HR =2.25 for CSS), and multiple primaries which was defined as 2nd of two or more primaries (HR =2.33 for OS) independently predicted poorer survival. Human epidermal growth factor receptor 2 (HER2) positivity (HR =0.54 for OS) and progesterone receptor (PR) positivity (HR =0.50 for CSS) were protective factors. Nomograms outperformed the American Joint Committee on Cancer (AJCC) 7th edition staging system, with C-indices of 0.77 (OS) and 0.82 (CSS) in training, and 0.75 (OS) and 0.78 (CSS) in validation. Chemotherapy worsened outcomes in low-risk patient but benefited high-risk subgroups, particularly neoadjuvant chemotherapy for patients with complete response (HR =0.41 for OS). CONCLUSIONS: This study establishes validated nomograms that improve survival prediction for young, operable BC patients, identifying high-risk subgroups likely to benefit from neoadjuvant chemotherapy. Conversely, low-risk patients may be spared unnecessary treatment. Prospective validation integrating molecular biomarkers is warranted to refine therapeutic personalization.