title: Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer.
abstract: OBJECTIVE
  The aim of this study was to determine whether TP53 mutation status (MS) can predict response of breast cancer to paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC). TP53 gene expression signature (GES) was also examined for its predictive capability of response to P-FEC since TP53 GES provides a more accurate measure of the functional configuration of TP53.
  
  
  METHODS
  Tumor samples were obtained from 72 primary breast cancer patients (stage II/III) before neoadjuvant chemotherapy (P-FEC) and analyzed for identification of TP53 MS (genomic sequencing), TP53 GES (DNA microarray), and p53 protein expression (immunohistochemistry).
  
  
  RESULTS
  Of 72 breast tumors, 16 were TP53 mutant-type (TP53 mt) and 56 were wild-type (TP53 wt). 29 tumors (40%) were positive for p53 protein by immunohistochemistry. DNA microarray analysis showed that 27 were TP53 mt-like tumors and 45 were TP53 wt-like tumors, depending on the expression signature of the TP53-related 31-genes. There was no statistically significant difference in pathological complete response (pCR) rates between TP53 mt and wt tumors (19% vs 23%) and between p53 positive and negative tumors (24% vs 21%) but TP53 mt-like tumors showed a significantly (P=0.019) higher pCR rate (37%) than TP53 wt-like tumors (13%) (Hazard ratio, 3.82; 95% C.I., 1.20-12.21).
  
  
  CONCLUSIONS
  TP53 GES, but not TP53 MS and p53 protein expression, is predictive of response to neoadjuvant P-FEC, suggesting that TP53 GES more correctly reflects the functionality of TP53.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, 2-2-E10 Yamadaoka, Suita-shi, Osaka, Japan.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Oshima
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Naoi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kishi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwamoto
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Baba
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016000:Cluster Analysis; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009154:Mutation; D017239:Paclitaxel / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil