title: The role of AIB1 and PAX2 in primary breast cancer: validation of AIB1 as a negative prognostic factor.
abstract: Background The steroid-receptor coactivator amplified in breast cancer one (AIB1) is implicated to be a prognostic factor, although the results are not unanimous. Recently its effect was suggested to be modified by paired box 2 gene product (PAX2). Patients and methods Using immunohistochemistry (IHC) AIB1 and PAX2 were investigated in two cohorts of early breast cancer, including systemically untreated premenopausal lymph-node-negative women and pre- and postmenopausal women receiving tamoxifen. Results AIB1 scores were available for 490 patients and PAX2 scores were available for 463 patients. High AIB1 was a negative prognostic factor for distant disease-free survival (DDFS, P = 0.02) and overall survival (OS, P < 0.001) in systemically untreated women, while no prognostic effect was seen in the tamoxifen-treated cohort, indicating AIB1 to be a predictor of tamoxifen response. In systemically untreated patients, PAX2 was not a prognostic factor, nor did it modify the effect of AIB1. However, in ER-positive patients receiving tamoxifen, PAX2 appeared to be a positive prognostic factor in premenopausal patients, while a negative factor in postmenopausal. The interaction between the menopausal status and PAX2 was significant (P = 0.01). Conclusions In an independent cohort of low-risk premenopausal patients, we validate AIB1 as a negative prognostic factor, indicating AIB1 to be an interesting target for new anti-cancer therapies. The effect of PAX2 warrants further studies.
authors.affiliation: Department of Oncology, Clinical Sciences, Lund University, Lund, Sweden. sara.alkner@med.lu.se
authors.forename: S
authors.initials: S
authors.lastname: Alkner
authors.forename: Po
authors.initials: P
authors.lastname: Bendahl
authors.forename: D
authors.initials: D
authors.lastname: Grabau
authors.forename: P
authors.initials: P
authors.lastname: Malmström
authors.forename: M
authors.initials: M
authors.lastname: Fernö
authors.forename: L
authors.initials: L
authors.lastname: Rydén
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D056921:Nuclear Receptor Coactivator 3 / Q000235:genetics / Q000378:metabolism*; D051762:PAX2 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D051762:PAX2 Transcription Factor; C497318:PAX2 protein, human; D013629:Tamoxifen; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3