Prognostic significance of bcl-2 expression in stage III breast cancer patients who received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

Abstract

670 Background: Bcl-2 is an anti-apoptotic marker and regulated by hormonal receptor pathways in breast cancer. We performed this study to assess the prognostic significance of ER, PR, p53, c-erbB2, bcl-2, Ki-67, and EGFR as a marker for relapse in breast cancer patients who received same adjuvant therapy in a single institution. Methods: A cohort of 154 curatively resected breast cancer patients who had 4 lymph nodes or more and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinicopathologic characteristics including disease-free survival (DFS). Patients with ER and/or PR expression received 5 years of tamoxifen following AC/T. The markers were analyzed by immunohistochemistry. Results: Median f/u duration was 25 months and 32 patients (20.8%) had recurrences. Stage (IIIa vs. IIIc) affected recurrences significantly, however, types of surgery, histology, histologic grade, presence of endolymphatic emboli, or close resection margin did not. Among the immunohistochemical markers, bcl-2 expression was the only one to be associated significantly with prolonged DFS (median 54 mo in bcl-2 (−) vs. not reached in bcl-2 (+); p=0.016). Furthermore, bcl-2 was an independent prognostic factor for DFS in multivariate analysis. Bcl-2 expression was significantly correlated with ER expression (p<0.001), and inversely correlated with c-erbB2 overexpression (p=0.027). Patients with both ER and bcl-2 expression had a longer DFS compared to the other patients (not reached vs. 54 mo, p=0.019). Patients with bcl-2 expression had a significantly longer DFS even in ER (+) subgroups (not reached vs 54 mo; p=0.011). Patients with c-erbB2 overexpression, ER (−) and bcl-2 (−) had a shorter DFS than the others (38 mo vs. not reached; p=0.029). Conclusions: In our homogenous patient cohort, bcl-2 expression was correlated with ER expression, and inversely correlated with c-erbB2 overexpression. Bcl-2 was an independent prognostic factor for DFS in curatively resected stage III breast cancer patients. No significant financial relationships to disclose.