Pathological features of triple-negative breast cancers that showed progressive disease during neoadjuvant chemotherapy

Abstract

Clinical progressive disease (cPD) occurs during neoadjuvant chemotherapy (NAC) in 3%-5% of triple-negative breast cancer (TNBC) patients. We aimed to identify the histopathological and immunohistochemical parameters that are correlated with the TNBC that showed cPD. We identified 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group). Using surgically resected tumor specimens, we performed histopathologic examinations and immunohistochemical analysis of 11 molecules that appeared relevant to epithelial-mesenchymal transition (EMT), and basal-like, molecular apocrine and other features. Metaplastic carcinomas (MPCs) and high proliferation (≥50 mitoses per 10 high-power fields or ≥50% Ki-67 score) were more frequent in the cPD than in the control (41% vs 3%, P < 0.001, and 86% vs 50%, P = 0.0049, respectively). Positive cytokeratin 5/6, ZEB1, TWISTNB, vimentin, and HMGB1 expressions and negative androgen receptor were more frequent in the cPD than in the control. By an unsupervised hierarchical cluster analysis incorporating these 11 molecules, the 102 TNBCs were divided into two major clusters and seven subclusters that appeared to correspond to intrinsic subtype, cPD status, histological type, and clinical outcome. In 27% of cPD cases, the MPC component appeared only in the post-NAC specimens. The combinations of high proliferation, metaplastic features, and immunohistochemical statuses of some EMT and basal-like markers and androgen receptor appeared to be able to characterize the TNBCs that showed cPD after NAC.

Keywords: Basal-like markers; clinical progressive disease; epithelial mesenchymal transition; neoadjuvant chemotherapy; triple negative breast cancer.