Bioscore: A Staging System for Breast Cancer Patients that Reflects the Prognostic Significance of Underlying Tumor Biology

Biologic factors guide treatment decisions and have a significant impact on prognosis for breast cancer patients. This study was undertaken to develop a staging system incorporating biologic factors in addition to standard anatomic factors in the American Joint Committee on Cancer (AJCC) pathologic stage (PS) to assess disease-specific survival (DSS). Overall, 3327 patients treated with surgery as an initial intervention at MD Anderson Cancer Center from 2007 to 2013 were identified. Multivariate analyses of factors, including PS, T stage (T), nodal stage (N), grade (G), estrogen receptor (ER) status (E) and human epidermal growth factor receptor (HER2) status (H) were performed to identify associations with DSS. A score of 0-4 was assigned for each factor by considering the hazard ratio magnitude. Multiple staging system models were then constructed: PS, PS + G, PS + G + E, PS + G + E + H, T + N, T + N + G, T + N + G + E, and T + N + G + E + H. Model performance was quantified using Harrell's concordance index, and the Akaike Information Criterion (AIC) was used to compare model fits. Comparable cases from California (n = 67,944) were used for validation. Median follow-up was 5.0 years (range 0.1-8.8) and 5-year DSS was 97.9% (95% confidence interval 97.3-98.4). Models incorporating grade, ER status, and HER2 status were most precise with identical C-index (0.81) and comparable AIC (994.9 for PS + G + E + H and 987.8 for T + N + G + E + H). Both models were externally validated. These results confirm the importance of biologic factors in determining prognosis for breast cancer patients. We propose the Bioscore, which incorporates grade, ER and HER2 status with AJCC PS, to provide more refined stratification of breast cancer patients undergoing surgery as an initial intervention with respect to DSS.