1. ¹Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia
2. ²Department of Anatomical Pathology, South Eastern Area Laboratory Service, St George Hospital, Kogarah, New South Wales 2217, Australia
3. ³Department of Medical Oncology, Westmead Hospital, University of Sydney, Westmead, New South Wales 2145, Australia
4. ⁴Department of Pathology (SydPath), St Vincent's Hospital, Darlinghurst, Sydney, New South Wales 2010, Australia
5. ⁵Department of Surgical Oncology, St Vincent's Hospital, Darlinghurst, Sydney, New South Wales 2010, Australia
6. ⁶Faculty of Medicine, St Vincent's Clinical School, University of NSW, New South Wales 2052, Australia
7. ⁷Division of Surgery, Bankstown Hospital, Bankstown, New South Wales 2200, Australia

Correspondence: Dr EKA Millar, E-mail: e.millar@garvan.org.au

Received 16 September 2008; Revised 12 November 2008; Accepted 12 November 2008; Published online 9 December 2008.

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.