title: Association between c-myc amplification and pathological complete response to neoadjuvant chemotherapy in breast cancer.
abstract: BACKGROUND
  The aim of this study was to investigate whether c-myc amplification in human breast cancer is associated with response to neoadjuvant chemotherapy comprising paclitaxel followed by 5-FU/epirubicin/cyclophosphamide (P-FEC).
  
  
  METHODS
  Tumour tissue samples were obtained before neoadjuvant chemotherapy (P-FEC) from 100 primary breast cancer patients (stage II/III). C-myc and HER2 amplification were examined by FISH, and oestrogen receptor (ER), progesterone receptor (PR), Ki67, and topoisomerase 2α (TOP2A) expression were examined immunohistochemically. Pathological complete response (pCR) was defined by a complete loss of tumour cells in the breast without any lymph node metastasis.
  
  
  RESULTS
  C-myc amplification was observed in 40% (40/100) of breast tumours, and was significantly associated with ER-negative tumours (23/40 for ER(-) versus 17/60 for ER(+), P=0.004), high histological grade tumours (11/18 for grade 3 versus 29/82 for grades 1+2, P=0.043) and TOP2A-positive tumours (28/51 for TOP2A(+) versus 12/49 for TOP2A(-), P=0.002). pCR rate was 20% for total patients (10.0% for ER(+) and 35.0% for ER(-)). Further, breast tumours with c-myc amplification (c-myc(+)) showed a significantly (P=0.041) higher pCR rate (12/40) than those without such amplification (c-myc(-)) (8/60). This association between pCR and c-myc amplification was observed in ER-positive tumours (4/17 for c-myc(+) versus 2/43 for c-myc(-), P=0.048) but not in ER-negative tumours (8/23 for c-myc(+) versus 6/17 for c-myc(-), P=0.973).
  
  
  CONCLUSIONS
  Our results suggest that c-myc amplification is significantly associated with a high pCR rate to P-FEC in breast tumours, especially in ER-positive tumours.
authors: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors: Hiroyuki
authors: H
authors: Yasojima
authors: Atsushi
authors: A
authors: Shimomura
authors: Yasuto
authors: Y
authors: Naoi
authors: Kazuki
authors: K
authors: Kishi
authors: Yousuke
authors: Y
authors: Baba
authors: Kenzo
authors: K
authors: Shimazu
authors: Takahiro
authors: T
authors: Nakayama
authors: Seung Jin
authors: SJ
authors: Kim
authors: Yasuhiro
authors: Y
authors: Tamaki
authors: Shinzaburo
authors: S
authors: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000951:Antigens, Neoplasm / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy / Q000379:methods; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005784:Gene Amplification; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000032:analysis; D008207:Lymphatic Metastasis; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D016017:Odds Ratio; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D000075223:Poly-ADP-Ribose Binding Proteins; D011237:Predictive Value of Tests; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012189:Retrospective Studies; D016896:Treatment Outcome; D016217:Ultrasonography, Mammary
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D015251:Epirubicin; D005472:Fluorouracil; D019394:Ki-67 Antigen; D017239:Paclitaxel; D000075223:Poly-ADP-Ribose Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C489427:MYC protein, human; C508053:ERBB2 protein, human; C000618811:TOP2A protein, human