Jornal de Pesquisa Clínica

Resistance to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer: Importance of Ki-67 Labeling Index and the Recognition of Apocrine-type Lesions

Abstract

Koichi Kubouchi and Yutaka Tsutsumi

Triple-Negative Breast Cancer (TNBC) encompasses heterogeneous subtypes. Apocrine-type TNBC, defined as TNBC immunoreactive for both androgen receptor and forkhead-box protein A1, should be distinguished from basal-like TNBC. In apocrine-type TNBC, neoadjuvant chemotherapy (NAC) tends to be ineffective, but with a favorable prognosis despite chemoresistance. We analyzed 51 cases of TNBC in stages I and II. Thirty-four TNBCs treated with NAC were divided into “good responders” (n=22) showing therapeutic effect G2b or G3 in surgical specimens and “poor responders” (n=12) with therapeutic effect G0, G1a, G1b and G2a. NAC was spared in 17 cases (categorized as the non-NAC group). TNBC other than apocrine-type (n=16) and special types (myoepithelial, medullary, adenoid cystic and spindle cell carcinomas, n=6) was categorized as basal-like subtype (n=29). The prognosis was evaluated in each category. NAC showed significant effects against basal-like TNBC with high Ki-67 labeling (≥ 50%), and tumor-infiltrating lymphocytes predicted high chemosensitivity. NAC was ineffective and avoidable in TNBC of apocrine- and special types showing low (<50%) Ki-67 labeling. Ten (59%) lesions in the non-NAC group belonged to the apocrine-type. When clinical complete remission shown by contrast-enhanced magnetic resonance imaging was reached in the course of NAC against basal-like TNBC, the NAC period was shortened (de-escalated) in 14 (64%) of 22 good responders. Disease-free and overall survival was excellent in all groups. The following two hypothetical proposals should be proven by large-scale clinical trials. Immunohistochemical recognition of apocrine-type TNBC with low Ki-67 labeling is important for avoiding ineffective/unnecessary NAC. By employing appropriate clinical imaging, de-escalation of NAC is achievable in basal-like TNBC with high Ki-67 labeling.