Potential Predictive Value of Bcl-2 for Response to Tamoxifen in the Adjuvant Setting of Node-Positive Breast Cancer

Abstract

Approximately 50% of patients with estrogen receptor (ER)—positive breast cancer (BC) and 70%–80% of patients with ER-positive and progesterone receptor (PgR)—positive BC respond to hormonal therapy. Additional predictive markers are needed. A group of 287 patients with ER- and/or PgR-positive tumors was selected from 804 patients previously enrolled in a multicenter phase III trial. Bcl-2 expression was evaluated and correlated with response to adjuvant tamoxifen and survival. Estrogen receptor and PgR were determined by biochemical means and Bcl-2 by immunohistochemistry. With a median follow-up of 76 months (95 relapses and 60 deaths), of the 287 patients with, 187 (65%) had Bcl-2—positive tumors and 78 of these patients received tamoxifen. Of the 100 patients with Bcl-2—negative disease, 51 received tamoxifen and 49 regular follow-up. Using patients treated with tamoxifen as a reference, a univariate analysis of disease-free interval for patients who did not receive tamoxifen showed a hazard ratio (HR) of 1.42 (95% CI, 0.82-2.44; P = 0.21) for patients with Bcl-2—positive disease and a HR of 1.05 (95% CI, 0.55-1.99; P = 0.89) for patients with Bcl-2—negative disease ( P = 0.48). After adjusting for number of positive lymph nodes, degree of receptor and PgR positivity, and type of surgery, the HRs were 1.54 (95% CI, 0.87–2.73; P = 0.14) for Bcl-2—positive disease and 1.05 (95% CI, 0.52–2.11; P = 0.88) for Bcl-2—negative disease. Despite its being a retrospective nonrandomized study with a relatively low number of patients, our results suggest that Bcl-2 deserves further evaluation as a predictive factor of sensitivity to tamoxifen.