Background: Improved staging systems that better predict survival for breast cancer patients who receive neoadjuvant chemotherapy (NAC) by accounting for clinical pathological stage plus estrogen receptor (ER) and grade (CPS+EG) and ERBB2 status (Neo-Bioscore) have been proposed. We sought to evaluate the generalizability and performance of these staging systems in a national cohort. Methods: The National Cancer Database (2006–2012) was reviewed for patients with breast cancer who received NAC and survived ≥90 days after surgery. Four systems were evaluated: clinical/pathologic American Joint Committee on Cancer (AJCC) 7th edition, CPS+EG, and Neo-Bioscore. Unadjusted Kaplan–Meier analysis and adjusted Cox proportional hazards models quantified overall survival (OS). Systems were compared using area under the curve (AUC) and integrated discrimination improvement (IDI). Results: Overall, 43,320 patients (5-year OS 76.0, 95% confidence interval [CI] 75.4–76.5%) were included, 12,002 of whom had evaluable Neo-Bioscore. AUC at 5 years for CPS+EG (0.720, 95% CI 0.714–0.726) and Neo-Bioscore (0.729, 95% CI 0.716–0.742) were improved relative to AJCC clinical (0.650, 95% CI 0.643–0.656) and pathologic (0.683, 95% CI 0.676–0.689) staging. Both CPS+EG (IDI 7.2, 95% CI 6.6–7.7%) and Neo-Bioscore (IDI 9.8, 95% CI 8.0–11.6%) demonstrated superior discrimination when compared with AJCC clinical staging at 5 years. Comparison of CPS+EG with Neo-Bioscore yielded an IDI of 2.6% (95% CI 0.9–4.5%), indicating that Neo-Bioscore is the best staging system. Conclusions: In a heterogenous national cohort of breast cancer patients treated with NAC and surgery, the incorporation of chemotherapy response, tumor grade, ER status, and ERBB2 status into the staging system substantially improved on the AJCC TNM staging system in discrimination of OS. Neo-Bioscore provided the best staging discrimination.
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