BAG-1 predicts patient outcome and tamoxifen responsiveness in ER positive invasive ductal carcinoma of the breast.
BAG-1 enhances estrogen 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 datasets 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 outcome. BAG-1 over-expressing MCF-7 cells were treated with anti- estrogens to assess effects on cell proliferation. Gene expression data demonstrated a consistent association between high BAG-1 mRNA and improved survival. In ER+ cancer (n=189), 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, HR 0.29, 95% CI: 0.114-0.735) and improved outcome in tamoxifen-treated patients (n=107; p=0.0191). BAG-1 over-expression in MCF-7 cells augmented anti-estrogen induced growth arrest. High BAG-1 expression predicts response to tamoxifen and 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.
|Authors||Millar, EKA.,; Anderson, LR., ; McNeil, CM., ; O'Toole, SA.,; Pinese, M., ; Crea, P.,; Morey, A.,; Biankin, AV., ; Henshall, SM.,; Musgrove, EA.,; Sutherland, RL.; Butt, AJ.|
|Publisher Name||BRITISH JOURNAL OF CANCER|
|URL link to publisher's version||http://www.nature.com/bjc/journal/v100/n1/abs/6604809a.html|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10015|