Prognostic significance of Bcl-2 expression in non-basal triple-negative breast cancer patients treated with anthracycline-based chemotherapy.

Abstract

B cell lymphoma/leukemia-2 (Bcl-2) expression has generally been associated with estrogen receptor positivity and favorable prognosis in breast cancer. We examined immunohistochemical expression of Bcl-2 in 492 triple-negative breast cancers (TNBCs) using tissue microarrays and investigated its correlation with clinicopathologic features and clinical outcome. A total of 47 (9.5%) TNBCs showed Bcl-2 expression. Bcl-2 expression was not associated with any of the clinicopathologic parameters and did not affect patient survival in TNBCs (Bcl-2-positive vs Bcl-2-negative TNBCs; overall survival (OS), P = 0.258; disease-free survival (DFS), P = 0.436). When TNBCs were divided into basal (cytokeratin 5/6 (CK5/6)+ and/or epidermal growth factor receptor (EGFR)+) and non-basal (CK5/6- and EGFR-) subgroups, Bcl-2 expression showed a significant association with worse OS (P = 0.002) and DFS (P = 0.002) in the non-basal subgroup. Among patients treated with an anthracycline, Bcl-2 expression also showed an association with decreased survival (OS, P = 0.004; DFS, P = 0.003) in the non-basal subgroup. In multivariate analyses, Bcl-2 expression was an independent poor prognostic factor for OS (P = 0.003) and DFS (P = 0.002) in this subgroup of TNBCs. Our results suggest that positive expression of Bcl-2 predicts no benefit from adjuvant anthracycline-based chemotherapy in non-basal TNBC patients. In conclusion, Bcl-2 status showed both prognostic and predictive values in non-basal TNBCs; therefore, assessment of Bcl-2 status and basal phenotype can provide information on prognostic and therapeutic classifications of TNBCs.