Loss of B-cell translocation gene 2 expression in estrogen receptor-positive breast cancer predicts tamoxifen resistance.
Bottom Line: To determine if BTG2 expression modifies tamoxifen efficacy, a cohort of 60 patients treated with adjuvant tamoxifen monotherapy was analyzed.We found that increased BTG2 expression showed better clinical survival and was the only independent prognostic factor for disease-free survival (hazard ratio, 0.691; 95% confidence interval, 0.495-0.963; P = 0.029).Consistent with this observation, tamoxifen significantly suppressed the growth ratio, tumor weight and Ki-67 expression in BTG2 expressing breast cancer xenografts in mice.
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.Show MeSH
Related in: MedlinePlus
Mentions: A previous expression analysis study in human breast carcinoma showed a loss of nuclear expression of BTG2 protein in 46% of tumors.6 Analysis of the Oncomine data set also revealed a strong correlation between decreased BTG2 expression and recurrence in patients undergoing tamoxifen treatment.11 To further validate the ability of BTG2 loss to predict the response to tamoxifen monotherapy, we analyzed gene expression data generated from a collection of laser-microdissected breast cancer samples (n = 60) from subjects who received tamoxifen alone as adjuvant systemic therapy (GEO database accession no. GDS807). According to the original study, patient inclusion criteria was defined as women diagnosed at the Massachusetts General Hospital between 1987 and 2000 with hormone receptor-positive breast cancer, treated with standard breast surgery, followed by 5 years of systemic adjuvant tamoxifen. No patient who received chemotherapy prior to recurrence was allowed.18 The list of patient and tumor characteristics (tumor size, histological grade, lymph node status, age and status of ER, PR and HER2) is available in a previous publication.18 Statistical analyses revealed that higher histological grade (P = 0.007) and lymph node negativity (P = 0.043) were significantly associated with BTG2 suppression (Table1). We also conducted stepwise variable selection of the Cox proportional hazards regression model to identify clinical variables and BTG2 expression that were significant predictors of DFS. The results identified increased BTG2 expression as the only independent prognostic factor for DFS (hazard ratio, 0.691; 95% confidence interval, 0.495–0.963; P = 0.029). The DFS curve was drawn using Kaplan–Meier estimates and compared using log-rank tests. It revealed that patients with tumors displaying increased BTG2 expression showed good clinical outcomes with a statistically significant difference (Fig.1).
Affiliation: Department of Surgery, Keio University School of Medicine, Tokyo, Japan.