title: Estrogen receptor-related genes as an important panel of predictors for breast cancer response to neoadjuvant chemotherapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, 270 Dong An Road, 200032, Shanghai, China.
authors.forename: Yizuo
authors.initials: Y
authors.lastname: Chen
authors.forename: Canming
authors.initials: C
authors.lastname: Chen
authors.forename: Benlong
authors.initials: B
authors.lastname: Yang
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Xu
authors.forename: Fei
authors.initials: F
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Xun
authors.initials: X
authors.lastname: Ye
authors.forename: Xia
authors.initials: X
authors.lastname: Meng
authors.forename: Bruno
authors.initials: B
authors.lastname: Mougin
authors.forename: Guangyu
authors.initials: G
authors.lastname: Liu
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Shen
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shao
authors.forename: Jiong
authors.initials: J
authors.lastname: Wu
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D010455:Peptides; D011960:Receptors, Estrogen; C051838:TFF1 protein, human; C082495:TFF3 protein, human; D000071163:Trefoil Factor-1; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins; D016190:Carboplatin; D017239:Paclitaxel