Research article

CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer

Francisco J Esteva¹ , Jing Wang² , Feng Lin² , Jaime A Mejia¹ , Kai Yan² , Kadri Altundag^1,3 , Vicente Valero¹ , Aman U Buzdar¹ , Gabriel N Hortobagyi¹ , W Fraser Symmans⁴ and Lajos Pusztai¹

¹  Department of Breast Medical Oncology, Unit 1354, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

²  Department of Bioinformatics and Computational Biology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

³  Department of Medical Oncology, Hacettepe University Institute of Oncology, Sihhiye St, Ankara 06100, Turkey

⁴  Department of Pathology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

author email corresponding author email

Breast Cancer Research 2007, 9:R87doi:10.1186/bcr1836

Published:	17 December 2007

Abstract

Introduction

We performed gene expression analysis to identify molecular predictors of resistance to preoperative concomitant trastuzumab and paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide (T/FEC).

Methods

Pretreatment fine-needle aspiration specimens from 45 patients with HER-2-overexpressing stage II to IIIA breast cancer were subjected to transcriptional profiling and examined for differential expression of various genes and gene sets. The primary endpoint for tumor response was pathologic complete response (pCR). Correlations between pCR and gene expression were sought.

Results

The overall pCR rate was 64%. Age, nuclear grade, tumor size, nodal status, quantitative expression of estrogen and HER-2 receptor mRNA, and HER-2 gene copy number showed no correlation with pCR. Results of gene set enrichment analysis suggested that the lower expression of genes involved with CD40 signaling is associated with a greater risk of residual cancer after the preoperative chemotherapy that includes trastuzumab.

Conclusion

CD40 signaling may play a role in determining response to trastuzumab-plus-T/FEC therapy in patients with HER-2-overexpressing breast cancer.