BCL2 is an independent predictor of outcome in basal-like triple-negative breast cancers treated with adjuvant anthracycline-based chemotherapy

Abstract

Neither targeted therapies nor predictors for chemotherapy sensitivity are available for triple-negative breast cancer (TNBC). Our study included 187 patients with TNBC, 164 of whom were treated with anthracycline-based adjuvant chemotherapy. Eleven molecular biomarkers were analyzed. BCL2, epidermal growth factor receptor (EGFR), MYC, TOP2A, and Ki-67 protein expression was evaluated by immunohistochemistry. The status of the EGFR, MYC, and TOP2A genes and chromosomes 7, 8, and 17 was assessed using fluorescence in situ hybridization. High BCL2 expression predicted poor relapse-free survival (RFS) in patients treated with anthracycline-based adjuvant chemotherapy (p = 0.035), poor breast cancer-specific survival (BCSS) (p = 0.048), and a trend to poor overall survival (OS) (p = 0.085). High levels of BCL2 expression predicted poor OS in basal-like (BL) TNBC patients treated with adjuvant anthracycline-based regimens (log-rank p = 0.033, hazard ratio (HR) 3.04, 95 % confidence interval (CI) 1.04-8.91) and a trend to poor RFS (log-rank p = 0.079) and poor BCSS (log-rank p = 0.056). Multivariate analysis showed that BCL2 status, tumor size, and nodal status all had independent predictive significance for RFS (p = 0.005, p = 0.091, p = 0.003, respectively; likelihood ratio test for the whole model, p = 0.003), BCSS (p = 0.012, p = 0.077, p = 0.01, respectively; likelihood ratio test for the whole model, p = 0.016), and OS (p = 0.008, p = 0.004, p = 0.004, respectively; likelihood ratio test for the whole model, p = 0.0006). Similarly, multivariate analysis for BL TNBC showed BCL2, tumor size, and nodal status all had independent predictive significance for RFS (likelihood ratio test for the whole model, p = 0.00125), BCSS (p = 0.00035), and OS (p = 0.00063). High EGFR expression was associated with poor BCSS (p = 0.039) in patients treated with anthracycline-based adjuvant chemotherapy. Patients who underwent anthracycline-based adjuvant chemotherapy and exhibited CMYC amplification had a trend to worse BCSS (p = 0.066). In conclusion, high BCL2 expression is a significant independent predictor of poor outcome in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and this is the first study showing the BCL2 prediction in BL TNBC. BCL2 expression analysis could facilitate decision making on adjuvant treatment in TNBC patients.

S100P and HYAL2 as prognostic markers for patients with triple-negative breast cancer

“…Although the expression levels of Ki-67, BCL2 and p53 in TNBC have been reported as a prognostic marker for TNBC in previous studies (Adamo and Anders, 2011;Abdel-Fatah et al, 2013;Bouchalova et al, 2015;Keam et al, 2011), we did not observe significant associations between the expression of these proteins and the PFS of TNBC patients in our study, probably due to limited events in our study.…”

Prognostic Influence of BCL2 on Molecular Subtypes of Breast Cancer

“…Choi et al [29] reported that although BCL2 expression was not associated with any clinicopathologic parameters and did not affect patient survival in TNBC, BCL2 expression showed a significant association with worse OS and disease free survival in the nonbasal (claudin-low; CK5/6– and EGFR–) subgroup of TNBC [29]. Bouchalova et al [30] reported that high BCL2 expression is a significant independent predictor of poor outcomes in TNBC patients treated with anthracycline-based adjuvant chemotherapy, and high EGFR protein expression is associated with poor BCSS in patients with TNBC treated with anthracycline-based chemotherapy, especially in basal-like (core; CK5/6+ and/or EGFR+) TNBC [30]. Further investigations will be required to elucidate the prognostic association between BCL2 and TNBC.…”

Age-associated prognostic and predictive biomarkers in patients with breast cancer

“…The correlation between Bcl-2 expression and patient outcome has been the focus of a number of studies on primary breast cancer and, paradoxically, Bcl-2 was identified to be a marker of improved prognosis (45) across molecular subtypes (46–49). The explanation for this paradox may be that Bcl-2 is an estrogen-responsive gene (50) or that high levels of pro-apoptotic Bcl-2 trigger mitochondrial priming (51).…”