Apoptosis induced by anticancer agents is a mechanism of treatment activity, overexpression of antiapoptotic genes could produce drug resistant tumors. We have demonstrated that the susceptibility of Bcl-2-negative tumors to a series of anticancer drugs was significantly higher than that of Bcl-2-positive tumors. The purpose of this study was to examine if negative Bcl-2 expression has treatment benefit in breast cancer patients received chemotherapy and endocrine treatment. A cohort of 147 Japanese women with invasive ductal carcinoma was studied. All the patients received postoperative adjuvant therapy consisting of combination chemotherapy with cyclophosphamide, epirubicin, and fluorouracil, and tamoxifen therapy. The expression of Bcl-2, estrogen receptor (ER) and MIB-1 was evaluated in breast cancer surgical specimens. Bcl-2 immunostaining was inversely correlated with increasing histologic grade (p=0.0095) and MIB-1 (p=0.0128). Furthermore, a positive correlation between Bcl-2 and ER was observed (p<0.0001). Unexpectedly, survival curves determined by the Kaplan-Meier method and univariate analysis demonstrated that Bcl-2-positivity was associated with favorable prognosis (p=0.0430). Cox proportional hazard model demonstrated that positive Bcl-2 expression still has favorable survival (p=0.0242) after consideration of other prognostic factors. Our results imply that Bcl-2 is a significant favorable prognostic factor for breast cancer with chemotherapy and endocrine therapy.

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