Potential predictive value of Bcl-2 for response to tamoxifen in the adjuvant setting of node-positive breast cancer.
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.
Cardoso
Fatima
F
Translational Research Unit, Jules Bordet Institute, Brussels, Belgium. fatima.cardoso@bordet.be
Paesmans
Marianne
M
Larsimont
Denis
D
Durbecq
Virginie
V
Bernard-Marty
Chantal
C
Rouas
Ghizlane
G
Dolci
Stella
S
Sotiriou
Christos
C
Piccart
Martine J
MJ
Di Leo
Angelo
A
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D020360:Neoadjuvant Therapy; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage*; D016896:Treatment Outcome
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D011960:Receptors, Estrogen; D013629:Tamoxifen