Ensemble machine learning for predicting breast cancer recurrence and mortality using clinical and hemogram data

Accurate prediction of breast cancer recurrence remains difficult because prognosis varies significantly across molecular subtypes. This underscores the need for scalable, affordable, and interpretable prognostic tools. We developed machine learning models integrating hematological indices with clinicopathologic data to predict 2- and 10-year recurrence or all-case death. We retrospectively analyzed 4277 women with primary breast cancer (2008-2022). The cohort included hormone receptor-positive (HR + ), HER2-positive, and triple-negative (TNBC) subtypes. We trained multiple classifiers and integrated them into a stacked ensemble using logistic regression as the final learner. Class imbalance was addressed with SMOTE applied to training sets. The ensemble achieved strong discrimination: general cohort AUC 0.859 (2-year) and 0.811 (10-year), with specificity 84-82% and sensitivity 68-61%. Subtype-specific performance remained robust across time horizons: HR + AUC 0.862/0.804, HER2 + AUC 0.877/0.831, and TNBC AUC 0.826/0.826 (2-year/10-year respectively). SHAP analysis identified advanced tumor stage, elevated inflammatory ratios (NLR, PLR, MLR), elevated red cell distribution width, and age as key adverse predictors with stronger effects on early recurrence. This interpretable tool uses routine blood tests and clinico-pathological data at diagnosis. It flaggs high-risk patients for intensified therapy, useful where genomic testing is unavailable.