Originally published as JCO Early Release 10.1200/JCO.2008.18.5934 on April 13 2009

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

From the Departments of Breast Medical Oncology, Pathology, and Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX; Department of Gynecology and Obstetrics, University Muenster, Muenster, Germany; Nuvera Biosciences, Woburn, MA; Translational Research Unit, Jules Bordet Institute, Brussels, Belgium; Machine Learning Group, Université Libre de Bruxelles, Brussels, Belgium.

Corresponding author: Lajos Pusztai, MD, DPhil, Departments of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030; e-mail: lpusztai{at}mdanderson.org.

Purpose The 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.

Methods Gene 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.

Results Eighty-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.

Conclusion High 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.

Supported by grants from the Deutsche Forschungsgemeinschaft (C.L.); Grant No. RO1-CA106290 from the National Cancer Institute (L.P.); the Breast Cancer Research Foundation; and the Goodwin Foundation.

Presented in poster format at the 44th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 30 to June 3, 2008.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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