BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast
Open Access
- 9 December 2008
- journal article
- Published by Springer Science and Business Media LLC in British Journal of Cancer
- Vol. 100 (1), 123-133
- https://doi.org/10.1038/sj.bjc.6604809
Abstract
BAG-1 (bcl-2-associated athanogene) enhances oestrogen receptor (ER) function and may influence outcome and response to endocrine therapy in breast cancer. We determined relationships between BAG-1 expression, molecular phenotype, response to tamoxifen therapy and outcome in a cohort of breast cancer patients and its influence on tamoxifen sensitivity in MCF-7 breast cancer cells in vitro. Publically available gene expression data sets were analysed to identify relationships between BAG-1 mRNA expression and patient outcome. BAG-1 protein expression was assessed using immunohistochemistry in 292 patients with invasive ductal carcinoma and correlated with clinicopathological variables, therapeutic response and disease outcome. BAG-1-overexpressing MCF-7 cells were treated with antioestrogens to assess its effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n=189), a high nuclear BAG-1 expression independently predicted improved outcome for local recurrence (P=0.0464), distant metastases (P=0.0435), death from breast cancer (P=0.009, hazards ratio 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n=107; P=0.0191). BAG-1 overexpression in MCF-7 cells augmented antioestrogen-induced growth arrest. A high BAG-1 expression predicts improved patient outcome in ER+ breast carcinoma. This may reflect both a better definition of the hormone-responsive phenotype and a concurrent increased sensitivity to tamoxifen.Keywords
This publication has 43 references indexed in Scilit:
- Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifenBMC Genomics, 2008
- Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancerBreast Cancer Research, 2008
- Basal-Like Breast Cancer Defined by Five Biomarkers Has Superior Prognostic Value than Triple-Negative PhenotypeClinical Cancer Research, 2008
- Do classical oestrogen markers predict for clinical response to endocrine therapy?Breast Cancer Research, 2007
- Gene expression patterns for doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) (AC) response and resistanceBreast Cancer Research and Treatment, 2005
- Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trialsThe Lancet, 2005
- A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast CancerThe New England Journal of Medicine, 2004
- A Gene-Expression Signature as a Predictor of Survival in Breast CancerThe New England Journal of Medicine, 2002
- Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implicationsProceedings of the National Academy of Sciences of the United States of America, 2001
- pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐upHistopathology, 1991