Clinical significance of basal-like subtype in triple-negative breast cancer

Abstract

No clinically useful target molecule has been identified for triple-negative (TN) breast cancer, i.e., estrogen receptor (ER)-negative, progesterone receptor (PgR)-negative, human epidermal growth factor receptor-2 (HER2)-negative phenotype, and its prognosis is poor. Triple-negative cancer consists of two subtypes: basal-like and non-basal-like. The aim of this study is to clarify the clinical and biological characteristics of these two subtypes of TN cancer. We examined, by immunohistochemistry, expression of biological markers cytokeratin (CK) 5/6 and epidermal growth factor receptor (EGFR) in triple-negative breast cancer. Basal-like subtype was defined as CK5/6-positive and/or EGFR-positive, and non-basal-like subtype was defined as no expression of these two markers. We studied the correlation between basal-like subtype and several factors related to tumor progression, along with the prognostic value of basal-like subtype and other biological markers in triple-negative cancer. In the 48 cases of operable triple-negative breast cancer, basal-like subtype was detected in 22 (45.8%) and non-basal-like subtype in 26 (54.2%). Basal-like subtype was significantly correlated with nodal status (P = 0.0475) and nuclear grade (P = 0.0475). Basal-like subtype was also significantly associated with Ki67 labeling index (P = 0.0118), c-kit expression (P = 0.0335), and aurora A expression (P = 0.0020). No association was detected between basal-like cancer and other biological markers. Patients with basal-like subtype of triple-negative cancer showed shorter disease-free survival (P = 0.0049) and overall survival (P = 0.0283) than patients with non-basal-like subtype. No independent prognostic factors were identified among the prognostic factors obtained from univariate analysis. These findings suggest that basal markers can be used to classify triple-negative breast cancer into at least two subtypes with differing prognoses. It is necessary to develop a novel treatment strategy to improve the prognosis of patients with basal-like subtype of triple-negative breast cancer.