Estrogen receptor-related genes as an important panel of predictors for breast cancer response to neoadjuvant chemotherapy

• Published in: Cancer letters 2011-03, Vol.302 (1), p.63-68
• Main Authors: Chen, Yizuo, Chen, Canming, Yang, Benlong, Xu, Qinghua, Wu, Fei, Liu, Fang, Ye, Xun, Meng, Xia, Mougin, Bruno, Liu, Guangyu, Shen, Zhenzhou, Shao, Zhimin, Wu, Jiong
• Format: Article
• Language: English
• Subjects: Adult; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer therapies; Carboplatin - administration & dosage; Chemotherapy; Epidermal growth factor; estrogen receptors; Female; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene expression; Gene Expression Profiling; gene expression regulation; Gene Expression Regulation, Neoplastic - drug effects; genes; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Mammography; microarray technology; Middle Aged; Neoadjuvant chemotherapy; Neoadjuvant Therapy; NMR; Nuclear magnetic resonance; Oligonucleotide Array Sequence Analysis; paclitaxel; Paclitaxel - administration & dosage; patients; Peptides - genetics; Peptides - metabolism; Prediction; Predictive Value of Tests; Prognosis; Receptors, Estrogen - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Studies; Treatment Outcome; Trefoil Factor-1; Trefoil Factor-3; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Ultrasonic imaging
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2010.12.014

Abstract Purpose Clinical data suggest that the estrogen receptor (ER) contributes to chemotherapeutic responsiveness. However, ER status alone is not consistently predictive. In this study, we used a microarray approach to find novel ER-related genes that predicted chemotherapy responses, with the hope of providing a robust multi-variable prediction method. Methods One hundred and ten patients with stages II and III breast cancer were included. They received four preoperative cycles of a weekly PCb (paclitaxel plus carboplatin) regimen. A total of 55 training cases were used for marker discovery and for identification of any ER-related genes that may have been associated with a chemotherapeutic response (“training cases”). The other 55 patients were available as an independent validation set (“validation cases”) to test, using immunohistochemistry (IHC). Results In the training set, 20 significantly differentially expressed genes were identified. Among these 20 genes, TFF1, ESR1, GATA3 and TFF3 were found to be ER-related. Among 55 independent validation cases, univariate analysis indicated that clinical variables and ER-related genes were all significantly associated with pCR. It was shown that the pCR rate was as high as 80% when these five factors were all negative. In contrast, these five factors were all positive in seven of nine chemo-resistant patients. Conclusion In conjunction with levels of ER-related genes, expression of ER protein may provide important predictive outcomes for responses to neoadjuvant chemotherapy and may allow for the identification of a subgroup of patients who could significantly benefit from chemotherapy (or who may be resistant to it).