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

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.

• Authors: Francisco J Esteva, Jing Wang, Feng Lin, Jaime A Mejia, Kai Yan, Kadri Altundag, Vicente Valero, Aman U Buzdar, Gabriel N Hortobagyi, W Fraser Symmans, Lajos Pusztai
• Journal: Breast cancer research : BCR (Breast Cancer Res) Vol. 9 Issue 6 Pg. R87 ( 2007) ISSN: 1465-542X [Electronic] England
• PMID: 18086299 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Biomarkers, Tumor
• CD40 Antigens
• RNA, Messenger
• Epirubicin
• Cyclophosphamide
• ERBB2 protein, human
• Receptor, ErbB-2
• Trastuzumab
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Biomarkers, Tumor (metabolism)
• Biopsy, Fine-Needle
• Breast Neoplasms (drug therapy, immunology, metabolism, pathology, surgery)
• CD40 Antigens (metabolism)
• Cyclophosphamide (administration & dosage)
• Epirubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic
• Humans
• Mastectomy (methods)
• Mastectomy, Modified Radical
• Mastectomy, Segmental
• Middle Aged
• Neoadjuvant Therapy (methods)
• Neoplasm Staging
• Neoplasm, Residual
• Paclitaxel (administration & dosage)
• Predictive Value of Tests
• RNA, Messenger (metabolism)
• Receptor, ErbB-2 (genetics, metabolism)
• Signal Transduction
• Transcription, Genetic
• Trastuzumab
• Treatment Outcome
• Up-Regulation