PIK3CA mutations in breast cancer: Reconciling findings from preclinical and clinical data

Dimitrios Zardavas, Wayne A. Phillips, Sherene Loi

Research output: Contribution to journalReview ArticleResearchpeer-review

72 Citations (Scopus)

Abstract

PIK3CA mutations represent one of the most common genetic aberrations in breast cancer. They have been reported to be present in over one-third of cases, with enrichment in the luminal and in human epidermal growth factor receptor 2-positive subtypes. Substantial preclinical data on the oncogenic properties of these mutations have been reported. However, whilst the preclinical data have clearly shown an association with robust activation of the pathway and resistance to common therapies used in breast cancer, the clinical data reported up to now do not support that the PIK3CA mutated genotype is associated with high levels of pathway activation or with a poor prognosis. We speculate that this may be due to the minimal use of transgenic mice models thus far. In this review, we discuss both the preclinical and clinical data associated with PIK3CA mutations and their potential implications. Prospective clinical trials stratifying by PIK3CA genotype will be necessary to determine if the mutation also predicts for increased sensitivity to agents targeting the phosphoinositide 3-kinase pathway.

Original languageEnglish
Article number201
Number of pages10
JournalBreast Cancer Research
Volume16
Issue number1
DOIs
Publication statusPublished - 23 Jan 2014
Externally publishedYes

Keywords

  • breast cancer
  • Trastuzumab
  • everolimus
  • P13K pathway
  • P1K3CA mutation

Cite this