title: BAG-1 predicts patient outcome and tamoxifen responsiveness in ER-positive invasive ductal carcinoma of the breast.
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.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales 2010, Australia. e.millar@garvan.org.au
authors.forename: E K A
authors.initials: EK
authors.lastname: Millar
authors.forename: L R
authors.initials: LR
authors.lastname: Anderson
authors.forename: C M
authors.initials: CM
authors.lastname: McNeil
authors.forename: S A
authors.initials: SA
authors.lastname: O'Toole
authors.forename: M
authors.initials: M
authors.lastname: Pinese
authors.forename: P
authors.initials: P
authors.lastname: Crea
authors.forename: A L
authors.initials: AL
authors.lastname: Morey
authors.forename: A V
authors.initials: AV
authors.lastname: Biankin
authors.forename: S M
authors.initials: SM
authors.lastname: Henshall
authors.forename: E A
authors.initials: EA
authors.lastname: Musgrove
authors.forename: R L
authors.initials: RL
authors.lastname: Sutherland
authors.forename: A J
authors.initials: AJ
authors.lastname: Butt
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000627:therapeutic use*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: C091732:BCL2-associated athanogene 1 protein; D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D014157:Transcription Factors; D013629:Tamoxifen