Mitotic counts in breast cancer after neoadjuvant systemic chemotherapy and development of metastatic disease

Although pathologic complete response after neoadjuvant systemic chemotherapy (NST) is associated with an excellent prognosis, the prognosis for patients with residual disease is variable. The mitotic count (MC) is commonly used in the evaluation of histologic tumor grade, but its prognostic value relative to other factors when determined after NST has not been studied. We evaluated MC in the residual tumor after NST in order to determine whether it provided prognostic information independent of other factors, including the residual cancer burden (RCB). We retrospectively reviewed pathologic specimens from 80 patients with localized breast cancer who received standard NST, of whom 61 had residual disease evaluable for MC analysis and RCB score. The exact number of mitotic figures was counted in 10 high power (40x) fields (hpf). We classified tumors as having high (a parts per thousand yen13 per 10 hpf) and low (< 13 per 10 hpf) MC because this threshold fell at the midpoint for an intermediate MC score in the Nottingham combined histologic grade. Distant metastases developed in 2 of 32 (6.3 %) patients with a low MC compared with 18 of 29 (62.1 %) with a high MC (log-rank test, p < 0.001). When adjusted for other covariates, including age, estrogen receptor, HER2/neu expressions, and RCB score, a high MC was associated with a significantly higher risk of developing distant metastases (hazard ratio 11.21, 95 % CI [2.19, 57.37]; p = 0.004). Our findings indicated that evaluation of MC after NST warrants validation and further evaluation as a prognostic marker in breast cancer.