title: Epidermal growth factor receptor (EGFR) and the estrogen receptor modulator amplified in breast cancer (AIB1) for predicting clinical outcome after adjuvant tamoxifen in breast cancer.
abstract: The epidermal growth factor receptor (EGFR) and the estrogen receptor (ER) modulator Amplified In Breast cancer-1 (AIB1) have been reported to be of importance for the prognosis of breast cancer patients. We have analyzed AIB1 and EGFR by immunohistochemistry in primary breast cancers (n = 297) arranged in a tissue microarray in order to predict outcome after adjuvant endocrine therapy with tamoxifen for two years. High expression of AIB1 was associated with DNA-nondiploidy, high S-phase fraction, HER2 amplification, and short term (<or=2 years) distant disease-free survival (DDFS), independent of ER status. High expression of EGFR was strongly associated to ER negativity and also correlated with progesterone receptor negativity, high S-phase fraction, and inversely correlated with nodal metastases. In univariate analysis, high EGFR was associated with shorter DDFS (hazard ratio 2.1; P = 0.017), and reached borderline significance in a multivariate analysis, adjusting for ER, menopausal and lymph node status, tumor size, and HER2 (P = 0.057). In conclusion, both AIB1 and EGFR were associated to DDFS for breast cancer patients treated with two years of adjuvant tamoxifen; AIB1 with the development of early distant recurrences, indicating association between high AIB1 and resistance to tamoxifen during treatment, and EGFR with distant recurrences up to a follow up of five years.
authors.affiliation: Department of Oncology, Clinical Sciences, University of Lund, Lund, Sweden.
authors.forename: Looket
authors.initials: L
authors.lastname: Dihge
authors.forename: Pär-Ola
authors.initials: PO
authors.lastname: Bendahl
authors.forename: Dorthe
authors.initials: D
authors.lastname: Grabau
authors.forename: Jorma
authors.initials: J
authors.lastname: Isola
authors.forename: Kristina
authors.initials: K
authors.lastname: Lövgren
authors.forename: Lisa
authors.initials: L
authors.lastname: Rydén
authors.forename: Mårten
authors.initials: M
authors.lastname: Fernö
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000502:physiology; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D051548:Histone Acetyltransferases / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D056921:Nuclear Receptor Coactivator 3; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D046888:Tissue Array Analysis; D015534:Trans-Activators / Q000096:biosynthesis*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D020845:Selective Estrogen Receptor Modulators; D015534:Trans-Activators; D013629:Tamoxifen; D051548:Histone Acetyltransferases; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3; D066246:ErbB Receptors