title: Immunohistochemical BAG1 expression improves the estimation of residual risk by IHC4 in postmenopausal patients treated with anastrazole or tamoxifen: a TransATAC study.
abstract: BAG1 is a multifunctional anti-apoptotic protein located on chromosome 9q12, which binds to Bcl-2. BAG1 is present as a separate module in the GHI-RS 21-gene panel. It may provide additional prognostic information as an immunohistochemical marker when added to IHC4. Analysis of BAG1 was performed on archival tumour blocks from patients from the anastrozole and tamoxifen arms of the ATAC trial of 5 years endocrine therapy in postmenopausal women with oestrogen receptor (ER)-positive primary breast cancer. Staining was scored separately as nuclear or cytoplasmic. Statistical analyses were performed on data from median 10-year follow-up with distant recurrence as primary endpoint. Data on both nuclear and cytoplasmic BAG1 as well as the IHC4 markers (ER, PgR, HER2 and Ki67) were available on 963 ER-positive cases of which 860 were HER2-negative. Cytoplasmic and nuclear BAG1 were highly correlated (Spearman r = 0.79, p < 00001). Women with higher BAG1 expression developed 30 % fewer distant recurrences compared to those with low expression. Nuclear BAG1 contributed significantly to the clinical and IHC4 models with added information being greater in node-positive cases. Similar results were seen if all recurrences were the endpoints. BAG1 expression provides significant prognostic information when added to the classical clinicopathological parameters and IHC4, particularly in node-positive patients.
authors.affiliation: Department of Academic Biochemistry, The Royal Marsden Hospital, Fulham Road, London, SW3 6JJ, UK. maria.afentakis@icr.ac.uk
authors.forename: Maria
authors.initials: M
authors.lastname: Afentakis
authors.forename: Mitch
authors.initials: M
authors.lastname: Dowsett
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.forename: Janine
authors.initials: J
authors.lastname: Salter
authors.forename: Tony
authors.initials: T
authors.lastname: Howell
authors.forename: Aman
authors.initials: A
authors.lastname: Buzdar
authors.forename: John
authors.initials: J
authors.lastname: Forbes
authors.forename: Jack
authors.initials: J
authors.lastname: Cuzick
mesh_terms: D000077384:Anastrozole; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D019394:Ki-67 Antigen / Q000235:genetics; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D009570:Nitriles / Q000008:administration & dosage*; D017698:Postmenopause; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013629:Tamoxifen / Q000008:administration & dosage*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D000077384:Anastrozole; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D019394:Ki-67 Antigen; D009570:Nitriles; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D014157:Transcription Factors; D014230:Triazoles; C091732:BCL2-associated athanogene 1 protein; C508053:ERBB2 protein, human