This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peintinger, F. Articles by Pusztai, L. Search for Related Content PubMed PubMed Citation Articles by Peintinger, F. Articles by Pusztai, L.

Thirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer

Authors' Affiliations: Departments of ¹ Surgical Oncology, ² Pathology, ³ Biostatistics and Applied Mathematics, and ⁴ Breast Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas and ⁵ Nuvera Biosciences, Inc., Woburn, Massachussets

Requests for reprints: Lajos Pusztai, Department of Breast Medical Oncology, Box 1354, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-792-2817; Fax: 713-794-4385; E-mail: lpusztai{at}mdanderson.org.

Purpose: We examined whether the response predicted by a 30-gene pharmacogenomic test correlated with the residual cancer burden (RCB) after preoperative chemotherapy with paclitaxel, 5-fluorouracil, doxorubicin, and cyclophosphamide (T/FAC).

Experimental Design: Gene expression profiling was done at diagnosis in 74 patients with stages I to III breast cancer and was used to calculate a pharmacogenomic score and predict response to chemotherapy [pathologic complete response (pCR) or residual disease (RD)]. All patients received 6 months of preoperative T/FAC. Following pathologic review, a RCB score was calculated based on residual tumor and lymph node features. Four RCB classes were assigned; RCB-0 (pCR), RCB-I (near-PCR), RCB-II (moderate RD), and RCB-III (extensive RD). The correlations between the pharmacogenomic score, predicted pathologic response, RCB score, and RCB class were examined.

Results: Thirty-three patients were predicted to have pCR, and 40 were predicted to have RD. Observed responses were RCB-0: n = 20 (27%); RCB-I: n = 5 (7%); RCB-II: n = 36 (49%); and RCB-III: n = 13 (16%) patients. Pharmacogenomic and RCB scores were correlated (Pearson's R = –0.501, P < 0.0001). There was no difference between the mean genomic predictor scores for RCB-0/I groups (P = 0.94), but these were different from the mean scores of the RCB-II/III groups (P < 0.001). Among the 25 patients with RCB-0/I response, 19 (76%) were predicted to achieve pCR. The pharmacogenomic test correctly predicted RD in 92% of the patients with RCB-III, which corresponds to chemotherapy-resistant disease.

Conclusions: The 30-gene pharmacogenomic test showed good correlation with the extent of residual invasive cancer burden measured as both continuous and categorical variables.

This article has been cited by other articles:

				Y. Zhang, J. W.M. Martens, J. X. Yu, J. Jiang, A. M. Sieuwerts, M. Smid, J. G.M. Klijn, Y. Wang, and J. A. Foekens Copy Number Alterations that Predict Metastatic Capability of Human Breast Cancer Cancer Res., May 1, 2009; 69(9): 3795 - 3801. [Abstract] [Full Text] [PDF]

				M. J. Duffy and J. Crown A Personalized Approach to Cancer Treatment: How Biomarkers Can Help Clin. Chem., November 1, 2008; 54(11): 1770 - 1779. [Abstract] [Full Text] [PDF]

				J. S. Ross, C. Hatzis, W. F. Symmans, L. Pusztai, and G. N. Hortobagyi Commercialized Multigene Predictors of Clinical Outcome for Breast Cancer Oncologist, May 1, 2008; 13(5): 477 - 493. [Abstract] [Full Text] [PDF]