PIK3CA mutations are a predictor of docetaxel plus epirubicin neoadjuvant chemotherapy clinical efficacy in breast cancer

Neoplasma. 2014;61(4):461-7. doi: 10.4149/neo_2014_057.

Abstract

This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common activating mutations in human breast cancer (BC), and the efficacy of neoadjuvant chemotherapy (NCT).Using a novel liquid chip technology,PIK3CA DNA somatic mutations and HER2, PTEN, EGFR mRNA expression profiles were analyzed in formalin fixed paraffin embedded samples of 93 BC patients treated with epirubicin plus docetaxel NCT.PIK3CA mutations were found in 30 patients (32.3%), in which the point mutations of E542K, E545K, H1047L and H1047R were 4.3, 9.7, 4.3 and 14.0%respectively. The PIK3CA mutations were significantly associated with patients' clinical response; 27 of 30 PIK3CA mutated patients had either a partial or complete response (p=0.002). Multivariate analysis further confirmed that, after adjustments for age, disease stages and NCT cycles, PIK3CA was associated with clinical response (Odds Ration 0.126, 95% CI [0.029,0.691]). However, there was no significant difference between PIK3CA mutations in pathological complete response (pCR,7 /92) and non-pCR group. Furthermore, no EGFR, KRAS and BRAF mutations were detected in any of the 93 samples. Our data for the first time suggested that PIK3CA mutation status may be a predictor for better understanding clinical response to the combination of epirubicin and docetaxel NCT in patients with BC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / secondary
  • Class I Phosphatidylinositol 3-Kinases
  • Docetaxel
  • Epirubicin / administration & dosage
  • ErbB Receptors / genetics
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Neoadjuvant Therapy*
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prognosis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Taxoids / administration & dosage
  • ras Proteins / genetics

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Taxoids
  • Docetaxel
  • Epirubicin
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ErbB Receptors
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins