Cathrine F Hjorth1, Anja S Nielsen2, Henrik T Sørensen1, Timothy L Lash1,3, Per Damkier4,5, Stephen Hamilton-Dutoit2, Deirdre Cronin-Fenton1. 1. a Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 2. b Department of Pathology, Aarhus University Hospital, Aarhus, Denmark. 3. c Department of Epidemiology, Rollins School of Public Health, and Winship Cancer Institute, Emory University, Atlanta, USA. 4. d Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. 5. e Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
Abstract
BACKGROUND: Adjuvant tamoxifen therapy approximately halves the risk of recurrence in estrogen receptor-positive (ER+) breast cancer patients, but many women respond insufficiently to therapy. Expression of multi-drug resistance protein 2 (MRP2) in breast cancer may potentiate tamoxifen resistance. Thus, we investigated the expression of MRP2 in breast cancer as a predictor of tamoxifen therapy effectiveness. MATERIAL AND METHODS: We conducted a case-control study nested in the Danish Breast Cancer Group clinical database. The study included women aged 35-69 years diagnosed with stage l-lll breast cancer during 1985-2001, in Jutland, Denmark. We identified 541 recurrent breast cancers (cases) among women with estrogen receptor positive (ER+) disease treated with tamoxifen for at least 1 year (ER+/TAM+) and 300 cases among women with estrogen receptor-negative (ER-) disease, never treated with tamoxifen (ER-/TAM-). We matched one recurrence-free control to each recurrent case. We retrieved paraffin-embedded primary tumor tissue for all patients, and all available recurrent tumor tissue from pathology archives. MRP2 expression was evaluated using immunohistochemistry. We computed odds ratios (ORs) and 95% confidence intervals (95% CIs) associating MRP2 expression (positive vs. none) with breast cancer recurrence in conditional logistic regression models. We compared MRP2 expression in paired primary- and recurrent tumors. RESULTS: MRP2 expression was more prevalent in the ER+/TAM + group, than in the ER-/TAM - group. No predictive utility of MRP2 for breast cancer recurrence was found in the ER+/TAM + group (ORadj = 0.96, 95% CI 0.70, 1.33). Further, no prognostic utility was found in the ER-/TAM - group (ORadj = 0.81, 95% CI 0.53, 1.23). MRP2 expression was not increased in recurrent versus primary tumors. CONCLUSIONS: MRP2 expression is neither a predictive marker of tamoxifen effectiveness nor a prognostic marker in breast cancer.
BACKGROUND: Adjuvant tamoxifen therapy approximately halves the risk of recurrence in estrogen receptor-positive (ER+) breast cancerpatients, but many women respond insufficiently to therapy. Expression of multi-drug resistance protein 2 (MRP2) in breast cancer may potentiate tamoxifen resistance. Thus, we investigated the expression of MRP2 in breast cancer as a predictor of tamoxifen therapy effectiveness. MATERIAL AND METHODS: We conducted a case-control study nested in the Danish Breast Cancer Group clinical database. The study included women aged 35-69 years diagnosed with stage l-lll breast cancer during 1985-2001, in Jutland, Denmark. We identified 541 recurrent breast cancers (cases) among women with estrogen receptor positive (ER+) disease treated with tamoxifen for at least 1 year (ER+/TAM+) and 300 cases among women with estrogen receptor-negative (ER-) disease, never treated with tamoxifen (ER-/TAM-). We matched one recurrence-free control to each recurrent case. We retrieved paraffin-embedded primary tumor tissue for all patients, and all available recurrent tumor tissue from pathology archives. MRP2 expression was evaluated using immunohistochemistry. We computed odds ratios (ORs) and 95% confidence intervals (95% CIs) associating MRP2 expression (positive vs. none) with breast cancer recurrence in conditional logistic regression models. We compared MRP2 expression in paired primary- and recurrent tumors. RESULTS:MRP2 expression was more prevalent in the ER+/TAM + group, than in the ER-/TAM - group. No predictive utility of MRP2 for breast cancer recurrence was found in the ER+/TAM + group (ORadj = 0.96, 95% CI 0.70, 1.33). Further, no prognostic utility was found in the ER-/TAM - group (ORadj = 0.81, 95% CI 0.53, 1.23). MRP2 expression was not increased in recurrent versus primary tumors. CONCLUSIONS:MRP2 expression is neither a predictive marker of tamoxifen effectiveness nor a prognostic marker in breast cancer.
Authors: Maarten T Huisman; Aniska A Chhatta; Olaf van Tellingen; Jos H Beijnen; Alfred H Schinkel Journal: Int J Cancer Date: 2005-09-20 Impact factor: 7.396
Authors: Cynthia Owusu; Diana S M Buist; Terry S Field; Timothy L Lash; Soe Soe Thwin; Ann M Geiger; Virginia P Quinn; Floyd Frost; Marianne Prout; Marianne Ulcickas Yood; Feifei Wei; Rebecca A Silliman Journal: J Clin Oncol Date: 2007-12-10 Impact factor: 44.544
Authors: Fred R Hirsch; Marileila Varella-Garcia; Paul A Bunn; Michael V Di Maria; Robert Veve; Roy M Bremmes; Anna E Barón; Chan Zeng; Wilbur A Franklin Journal: J Clin Oncol Date: 2003-09-02 Impact factor: 44.544