Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer Export

@article{citeulike:6086705, abstract = {PurposeThe genomic grade index (GGI) is a 97-gene measure of histological tumor grade. High GGI is associated with decreased relapse-free survival in patients receiving either endocrine or no systemic adjuvant therapy. Herein we examined whether GGI predicts pathologic response to neoadjuvant chemotherapy in patients with HER-2-normal breast cancer. MethodsGene expression data (gene chips) was generated from fine-needle aspiration biopsies (n = 229) prospectively collected before neoadjuvant paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Pathologic response was quantified using the residual cancer burden (RCB) method. The association between the GGI and pathologic response was assessed in univariate and multivariate analyses. The performance of a response predictor combining clinical variables and GGI was evaluated under cross-validation. ResultsEighty-five percent of grade 1 tumors had low GGI, 89\% of grade 3 tumors had high GGI, and 63\% of grade 2 tumors had low GGI. Among both estrogen receptor (ER)-positive and -negative cancers, high GGI score was associated with pathologic complete response (RCB-0) or minimal residual disease (RCB-1). A multivariate model combining GGI and clinical parameters had an overall accuracy of 71\%, compared with 58\% for the GGI alone, for prediction of pathologic response. However, high GGI score was also associated with significantly worse distant relapse-free survival in patients with ER-positive cancer (P = .005), and was not associated with survival in patients with ER-negative cancer. ConclusionHigh GGI is associated with increased sensitivity to neoadjuvant paclitaxel plus fluorouracil, adriamycin, and cyclophosphamide chemotherapy in both ER-negative and ER-positive patients, but it remains a predictor of worse survival in ER-positive patients. 10.1200/JCO.2008.18.5934}, author = {Liedtke, Cornelia and Hatzis, Christos and Symmans, William F. and Desmedt, Christine and Haibe-Kains, Benjamin and Valero, Vicente and Kuerer, Henry and Hortobagyi, Gabriel N. and Piccart-Gebhart, Martine and Sotiriou, Christos and Pusztai, Lajos}, citeulike-article-id = {6086705}, citeulike-linkout-0 = {http://dx.doi.org/10.1200/JCO.2008.18.5934}, citeulike-linkout-1 = {http://jco.ascopubs.org/content/27/19/3185.abstract}, citeulike-linkout-2 = {http://jco.ascopubs.org/content/27/19/3185.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/19364972}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=19364972}, day = {1}, doi = {10.1200/JCO.2008.18.5934}, journal = {J Clin Oncol}, keywords = {breast\_cancer, chemotherapy, gene\_expression}, month = {July}, number = {19}, pages = {3185--3191}, posted-at = {2009-11-08 22:33:09}, priority = {4}, title = {Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer}, url = {http://dx.doi.org/10.1200/JCO.2008.18.5934}, volume = {27}, year = {2009} }

TY - JOUR ID - citeulike:6086705 L3 - citeulike-article-id:6086705 N2 - PurposeThe genomic grade index (GGI) is a 97-gene measure of histological tumor grade. High GGI is associated with decreased relapse-free survival in patients receiving either endocrine or no systemic adjuvant therapy. Herein we examined whether GGI predicts pathologic response to neoadjuvant chemotherapy in patients with HER-2-normal breast cancer. MethodsGene expression data (gene chips) was generated from fine-needle aspiration biopsies (n = 229) prospectively collected before neoadjuvant paclitaxel, fluorouracil, doxorubicin, and cyclophosphamide chemotherapy. Pathologic response was quantified using the residual cancer burden (RCB) method. The association between the GGI and pathologic response was assessed in univariate and multivariate analyses. The performance of a response predictor combining clinical variables and GGI was evaluated under cross-validation. ResultsEighty-five percent of grade 1 tumors had low GGI, 89% of grade 3 tumors had high GGI, and 63% of grade 2 tumors had low GGI. Among both estrogen receptor (ER)-positive and -negative cancers, high GGI score was associated with pathologic complete response (RCB-0) or minimal residual disease (RCB-1). A multivariate model combining GGI and clinical parameters had an overall accuracy of 71%, compared with 58% for the GGI alone, for prediction of pathologic response. However, high GGI score was also associated with significantly worse distant relapse-free survival in patients with ER-positive cancer (P = .005), and was not associated with survival in patients with ER-negative cancer. ConclusionHigh GGI is associated with increased sensitivity to neoadjuvant paclitaxel plus fluorouracil, adriamycin, and cyclophosphamide chemotherapy in both ER-negative and ER-positive patients, but it remains a predictor of worse survival in ER-positive patients. 10.1200/JCO.2008.18.5934 IS - 19 JF - J Clin Oncol EP - 3191 TI - Genomic Grade Index Is Associated With Response to Chemotherapy in Patients With Breast Cancer VL - 27 SP - 3185 KW - breast_cancer KW - chemotherapy KW - gene_expression AU - Liedtke, Cornelia AU - Hatzis, Christos AU - Symmans, William AU - Desmedt, Christine AU - Haibe-Kains, Benjamin AU - Valero, Vicente AU - Kuerer, Henry AU - Hortobagyi, Gabriel AU - Piccart-Gebhart, Martine AU - Sotiriou, Christos AU - Pusztai, Lajos PY - 2009/07/01/ UR - http://dx.doi.org/10.1200/JCO.2008.18.5934 ER -