C-X-C ligand 10 and C-X-C receptor 3 status can predict tamoxifen treatment response in breast cancer patients.
To investigate the expression levels of CXCL10 and CXCR3 in tumors from breast cancer patients randomized to adjuvant tamoxifen treatment or no endocrine treatment, in order to further study the connection to prognosis and prediction of tamoxifen treatment outcome. Immunohistochemistry on tissue microarrays from 912 breast cancer patients randomized to tamoxifen or no endocrine treatment. CXCR3 status was found to be a prognostic tool in predicting distant recurrence, as well as reduced breast cancer-specific survival. In patients with estrogen receptor (ER)-positive tumors, tumors with strong CXCL10 levels had improved effect of tamoxifen treatment in terms of local recurrence-free survival [risk ratio (RR) 0.46 (95 % CI 0.25-0.85, P = 0.01)] compared with patients with tumors expressing weak CXCL10 expression. Further, patients with ER-positive tumors with strong CXCR3 expression had an improved effect of tamoxifen in terms of breast cancer-specific survival [RR 0.34 (95 % CI 0.19-0.62, P < 0.001)] compared with the group with weak CXCR3 levels [RR 1.33 (95 % CI 0.38-4.79, P = 0.65)]. We show here for the first time that CXCL10 and CXCR3 expression are both predictors of favorable outcome in patients treated with tamoxifen.
Division of Surgery and Clinical Oncology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, 581 85, Linköping, Sweden, erik.hilborn@liu.se.
Erik
E
Hilborn
Tove
T
Sivik
Tommy
T
Fornander
Olle
O
Stål
Bo
B
Nordenskjöld
Agneta
A
Jansson
D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D054357:Chemokine CXCL10 / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D011379:Prognosis; D016016:Proportional Hazards Models; D054367:Receptors, CXCR3 / Q000378:metabolism*; D012189:Retrospective Studies; D013629:Tamoxifen / Q000627:therapeutic use; D046888:Tissue Array Analysis
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D054367:Receptors, CXCR3; D013629:Tamoxifen