Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer. Export

@article{citeulike:6071586, abstract = {PURPOSE: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy. EXPERIMENTAL DESIGN: Recently, we showed that NEUROD1 DNA is differentially methylated in neoplastic versus nonneoplastic breast tissue samples. In this study, we used MethyLight and analyzed NEUROD1 methylation in (a) 74 breast cancer tissue samples, (b) two independent sets of pretreatment core biopsies of 23 (training set) and 21 (test set) neoadjuvantly treated breast cancer patients, and (c) pretherapeutic and posttherapeutic serum samples from 107 breast cancer patients treated with adjuvant chemotherapy. RESULTS: High-grade tumors showed higher NEUROD1 methylation levels. Estrogen receptor-negative breast cancers with high NEUROD1 methylation were 10.8-fold more likely to respond with a complete pathologic response following neoadjuvant chemotherapy. Patients with positive serum pretreatment NEUROD1 methylation, which persisted after chemotherapy, indicated poor relapse-free and overall survival in univariate and multivariate analyses (relative risk for relapse, 6.2; 95\% confidence interval, 1.6-24; P = 0.008, and relative risk for death, 14; 95\% confidence interval, 1.6-120; P = 0.02). CONCLUSIONS: These data support the view that NEUROD1 methylation is a chemosensitivity marker in estrogen receptor-negative breast cancer.}, author = {Fiegl, Heidi and Jones, Allison and Hauser-Kronberger, Cornelia and Hutarew, Georg and Reitsamer, Roland and Jones, Robin L. and Dowsett, Mitch and Mueller-Holzner, Elisabeth and Windbichler, Gudrun and Daxenbichler, G\"{u}nter and Goebel, Georg and Ensinger, Christian and Jacobs, Ian and Widschwendter, Martin}, citeulike-article-id = {6071586}, citeulike-linkout-0 = {http://dx.doi.org/10.1158/1078-0432.CCR-07-4557}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18519782}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18519782}, day = {1}, doi = {10.1158/1078-0432.CCR-07-4557}, issn = {1078-0432}, journal = {Clinical cancer research : an official journal of the American Association for Cancer Research}, keywords = {breast, chemotherapy, circ\_dna, epigenetics, gene\_specific\_methylation, methylation, neoadjuvant, neurod1, pharmacogenetics, prediction, response}, month = {June}, number = {11}, pages = {3494--3502}, posted-at = {2009-11-04 21:21:37}, priority = {2}, title = {Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer.}, url = {http://dx.doi.org/10.1158/1078-0432.CCR-07-4557}, volume = {14}, year = {2008} }

TY - JOUR ID - citeulike:6071586 L3 - citeulike-article-id:6071586 N2 - PURPOSE: Chemotherapy can be an integral component of the adjuvant management strategy for women with early stage breast cancer. To date, no tool is available to predict or monitor the efficacy of these therapies. The aim of this proof-of-principle study was to assess whether NEUROD1 DNA methylation is able to predict the response to neoadjuvant and adjuvant chemotherapy. EXPERIMENTAL DESIGN: Recently, we showed that NEUROD1 DNA is differentially methylated in neoplastic versus nonneoplastic breast tissue samples. In this study, we used MethyLight and analyzed NEUROD1 methylation in (a) 74 breast cancer tissue samples, (b) two independent sets of pretreatment core biopsies of 23 (training set) and 21 (test set) neoadjuvantly treated breast cancer patients, and (c) pretherapeutic and posttherapeutic serum samples from 107 breast cancer patients treated with adjuvant chemotherapy. RESULTS: High-grade tumors showed higher NEUROD1 methylation levels. Estrogen receptor-negative breast cancers with high NEUROD1 methylation were 10.8-fold more likely to respond with a complete pathologic response following neoadjuvant chemotherapy. Patients with positive serum pretreatment NEUROD1 methylation, which persisted after chemotherapy, indicated poor relapse-free and overall survival in univariate and multivariate analyses (relative risk for relapse, 6.2; 95% confidence interval, 1.6-24; P = 0.008, and relative risk for death, 14; 95% confidence interval, 1.6-120; P = 0.02). CONCLUSIONS: These data support the view that NEUROD1 methylation is a chemosensitivity marker in estrogen receptor-negative breast cancer. IS - 11 JF - Clinical cancer research : an official journal of the American Association for Cancer Research SN - 1078-0432 EP - 3502 TI - Methylated NEUROD1 promoter is a marker for chemosensitivity in breast cancer. VL - 14 SP - 3494 KW - breast KW - chemotherapy KW - circ_dna KW - epigenetics KW - gene_specific_methylation KW - methylation KW - neoadjuvant KW - neurod1 KW - pharmacogenetics KW - prediction KW - response AU - Fiegl, Heidi AU - Jones, Allison AU - Hauser-Kronberger, Cornelia AU - Hutarew, Georg AU - Reitsamer, Roland AU - Jones, Robin AU - Dowsett, Mitch AU - Mueller-Holzner, Elisabeth AU - Windbichler, Gudrun AU - Daxenbichler, Günter AU - Goebel, Georg AU - Ensinger, Christian AU - Jacobs, Ian AU - Widschwendter, Martin PY - 2008/06/01/ UR - http://dx.doi.org/10.1158/1078-0432.CCR-07-4557 ER -