PIK3CA mutation impact on survival in breast cancer patients and in ERα, PR and ERBB2-based subgroups

Breast Cancer Res. 2012 Feb 13;14(1):R28. doi: 10.1186/bcr3113.

Abstract

Introduction: PIK3CA is the oncogene showing the highest frequency of gain-of-function mutations in breast cancer, but the prognostic value of PIK3CA mutation status is controversial.

Methods: We investigated the prognostic significance of PIK3CA mutation status in a series of 452 patients with unilateral invasive primary breast cancer and known long-term outcome (median follow-up 10 years).

Results: PIK3CA mutations were identified in 151 tumors (33.4%). The frequency of PIK3CA mutations differed markedly according to hormone receptor (estrogen receptor alpha [ERα] and progesterone receptor [PR]) and ERBB2 status, ranging from 12.5% in the triple-negative subgroup (ER-/PR-/ERBB2-) to 41.1% in the HR+/ERBB2- subgroup. PIK3CA mutation was associated with significantly longer metastasis-free survival in the overall population (P = 0.0056), and especially in the PR-positive and ERBB2-positive subgroups. In Cox multivariate regression analysis, the prognostic significance of PIK3CA mutation status persisted only in the ERBB2-positive subgroup.

Conclusions: This study confirms the high prevalence of PIK3CA mutations in breast cancer. PIK3CA mutation is an emerging tumor marker which might become used in treatment-choosing process. The independent prognostic value of PIK3CA mutation status in ERBB2-positive breast cancer patients should be now confirmed in larger series of patients included in randomized prospective ERBB2-based clinical trials.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Mutational Analysis
  • Disease-Free Survival
  • Estrogen Receptor alpha / metabolism*
  • Female
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Mutation, Missense*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prognosis
  • Proportional Hazards Models
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Progesterone / metabolism*

Substances

  • Estrogen Receptor alpha
  • Receptors, Progesterone
  • estrogen receptor alpha, human
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2