Association between c-myc amplification and pathological complete response to neoadjuvant chemotherapy in breast cancer

Eur J Cancer. 2011 Aug;47(12):1779-88. doi: 10.1016/j.ejca.2011.06.017. Epub 2011 Jul 7.

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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Analysis of Variance
  • Antigens, Neoplasm / analysis
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Biopsy* / methods
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • DNA Topoisomerases, Type II / analysis
  • DNA-Binding Proteins / analysis
  • Epirubicin / administration & dosage
  • Female
  • Fluorouracil / administration & dosage
  • Gene Amplification*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / analysis
  • Lymphatic Metastasis
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Neoplasm Staging
  • Odds Ratio
  • Oligonucleotide Array Sequence Analysis
  • Paclitaxel / administration & dosage
  • Poly-ADP-Ribose Binding Proteins
  • Predictive Value of Tests
  • Proto-Oncogene Proteins c-myc / genetics*
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Retrospective Studies
  • Treatment Outcome
  • Ultrasonography, Mammary

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • Ki-67 Antigen
  • MYC protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Epirubicin
  • Cyclophosphamide
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • DNA Topoisomerases, Type II
  • TOP2A protein, human
  • Paclitaxel
  • Fluorouracil