Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance Export

@article{citeulike:3893032, abstract = {Purpose: We have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients.Patients and Methods: mRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor-positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy.Results: Concerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes.Conclusion: The majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients. 10.1200/JCO.2008.17.1462}, author = {van Agthoven, Ton and Sieuwerts, Anieta M. and Meijer-Van and Look, Maxime P. and Smid, Marcel and Veldscholte, Jos and Sleijfer, Stefan and Foekens, John A. and Dorssers, Lambert C.}, citeulike-article-id = {3893032}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2008.17.1462}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19075277}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19075277}, day = {15}, doi = {10.1200/JCO.2008.17.1462}, journal = {J Clin Oncol}, keywords = {brca, breast, cancer, resistance, tamoxifen}, month = {December}, pages = {JCO.2008.17.1462+}, posted-at = {2009-01-16 20:39:10}, priority = {2}, title = {Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance}, url = {http://dx.doi.org/10.1200/JCO.2008.17.1462}, year = {2008} }

TY - JOUR ID - citeulike:3893032 L3 - citeulike-article-id:3893032 N2 - Purpose: We have previously identified a set of breast cancer antiestrogen resistance (BCAR) genes causing estrogen independence and tamoxifen resistance in vitro using a functional genetic screen. Here, we explored whether these BCAR genes provide predictive value for tamoxifen resistance and prognostic information for tumor aggressiveness in breast cancer patients.Patients and Methods: mRNA levels of 10 BCAR genes (AKT1, AKT2, BCAR1, BCAR3, EGFR, ERBB2, GRB7, SRC, TLE3, and TRERF1) were measured in estrogen receptor-positive breast tumors using quantitative reverse-transcriptase polymerase chain reaction. Normalized mRNA levels were evaluated for association with progression-free survival (PFS) in 242 patients receiving tamoxifen as first-line monotherapy for recurrent disease, and with distant metastasis-free survival (MFS) in 413 lymph node-negative (LNN) primary breast cancer patients who did not receive systemic adjuvant therapy.Results: Concerning tamoxifen resistance, BCAR3, ERBB2, GRB7, and TLE3 mRNA levels were predictive for PFS, independent of traditional predictive factors. By combining GRB7 (or ERBB2) and TLE3 mRNA levels, patients could be classified in three subgroups with distinct PFS. For the evaluation of tumor aggressiveness, AKT2, EGFR, and TRERF1 mRNA levels were all significantly associated with MFS, independent of traditional prognostic factors. Using the combined AKT2 and EGFR mRNA status, four prognostic groups were identified with different MFS outcomes.Conclusion: The majority of BCAR genes, which were revealed to confer tamoxifen resistance and estrogen independence in vitro by functional screening, have clinical relevance, and associate with tamoxifen resistance and/or tumor aggressiveness in breast cancer patients. 10.1200/JCO.2008.17.1462 JF - J Clin Oncol TI - Relevance of Breast Cancer Antiestrogen Resistance Genes in Human Breast Cancer Progression and Tamoxifen Resistance SP - JCO.2008.17.1462 KW - brca KW - breast KW - cancer KW - resistance KW - tamoxifen AU - van Agthoven, Ton AU - Sieuwerts, Anieta AU - Meijer-Van AU - Look, Maxime AU - Smid, Marcel AU - Veldscholte, Jos AU - Sleijfer, Stefan AU - Foekens, John AU - Dorssers, Lambert PY - 2008/12/15/ UR - http://dx.doi.org/10.1200/JCO.2008.17.1462 ER -