Histological Grade Has Clinical Validity in Neoadjuvant-Treated Breast Cancer: A Multicenter Study

The prognostic performance of histologic grade in breast cancer is robust, but evidence for its clinical validity in the neoadjuvant setting is limited. Therefore, we evaluated grade in neoadjuvant-treated breast cancer to investigate associations with overall survival (OS) in the postneoadjuvant setting. In a multicentric neoadjuvant cohort (n = 507; diagnosed 2009-2018), we examined grade in preoperative biopsies and subsequent resected specimens and compared with controls of primary operated patients (n = 297). Survival analysis for the neoadjuvant cohort related to OS was estimated, with subgroup analysis for surrogate subtypes, using the Kaplan-Meier method and log-rank test. Multivariable Cox regression models were performed to calculate hazard ratios (HR) adjusted for established clinicopathological factors. A decrease in tumor grade between preoperative biopsies and resected specimens was more frequently observed in the neoadjuvant cohort (29.8%) compared with the nontreated control group (5.7%). Patients with high-grade tumors had a considerably worse prognosis compared with low-grade tumors in both biopsies and resected specimens (P values < .001). In subgroup analysis, we found that grade had prognostic value for the ER+/HER2- subtype (P value < .001). In multivariable analysis, grade in resection specimens remained an independent prognostic marker, related to OS (HR, 2.09; 95% CI, 1.30-3.35; P = .002), whereas grade in biopsies did not (HR, 1.40; 95% CI, 0.89-2.19; P = .14). This study shows that histologic tumor grade is associated with patient outcomes after neoadjuvant treatment. Postneoadjuvant grade should be considered a prognostic factor of use in therapeutic decision-making.