title: Expression profiling of breast cancer patients treated with tamoxifen: prognostic or predictive significance.
abstract: Approximately 70% of breast cancers are estrogen receptor (ER) positive, and interfering with estrogen action with tamoxifen has been the treatment of choice for ER-positive breast cancer patients. However, about a third of patients treated with tamoxifen will experience a recurrence of cancer. The expression analysis of selected genes involved in tamoxifen/estrogen and receptor tyrosine kinase signaling pathways can help to further decipher mechanisms of recurrence in ER+ tumors and contribute to the development of prognostic and possibly predictive biomarkers. We selected seven genes (ESR1, CCND1, MYC, HER2, AKT1, AIB1 and NCOR1), which are components of these pathways. A case-control study was designed. All patients in the control group had received standard adjuvant tamoxifen treatment for 5 years without any evidence of recurrence. Patients in the case group had experienced an early recurrence of cancer while receiving tamoxifen treatment. Expression levels of selected genes in both groups were compared. Expression levels of CCND1 (p < 0.001), HER2 (p < 0.001), AKT1 (p = 0.038) and AIB1 (p = 0.004) were significantly higher in recurrent tumors compared to non-recurrent tumors, while expression levels of NCOR1 (p < 0.001) were significantly lower in recurrent tumors. In multivariable analysis, CCND1 (p < 0.001), HER2 (p = 0.003), AIB1 (p = 0.036) and NCOR1 (p = 0.002) remained significant predictors of recurrence. Expression levels of CCND1, HER2, AIB1 and NCOR1 were detected as independent predictors of recurrence in this cohort of tamoxifen-treated patients. Further work should be done to validate the predictive value of this gene profile for tamoxifen response.
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Sanaz
authors.initials: S
authors.lastname: Tabarestani
authors.forename: Sayyed Mohammad Hossein
authors.initials: SM
authors.lastname: Ghaderian
authors.forename: Hamid
authors.initials: H
authors.lastname: Rezvani
authors.forename: Reza
authors.initials: R
authors.lastname: Mirfakhraie
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012008:Recurrence; D015398:Signal Transduction; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D013629:Tamoxifen