Tumor PIK3CA genotype and prognosis in early-stage breast cancer: A pooled analysis of individual patient data

Research output: Contribution to journalArticle

Abstract

Purpose Phosphatidylinositol-4, 5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations are frequently observed in primary breast cancer. We evaluated their prognostic relevance by performing a pooled analysis of individual patient data. Patients and Methods Associations between PIK3CA status and clinicopathologic characteristics were tested by applying Cox regression models adjusted for age, tumor size, nodes, grade, estrogen receptor (ER) status, human epidermal growth factor receptor 2 (HER2) status, treatment, and study. Invasive disease-free survival (IDFS) was the primary end point; distant disease-free survival (DDFS) and overall survival (OS) were also assessed, overall and by breast cancer subtypes. Results Data from 10,319 patients from 19 studies were included (median OS follow-up, 6.9 years); 1,787 patients (17%) received chemotherapy, 4,036 (39%) received endocrine monotherapy, 3,583 (35%) received both, and 913 (9%) received none or their treatment was unknown. PIK3CA mutations occurred in 32% of patients, with significant associations with ER positivity, increasing age, lower grade, and smaller size (all P, .001). Prevalence of PIK3CA mutations was 18%, 22%, and 37% in the ER-negative/HER2-negative, HER2-positive, and ER-positive/HER2-negative subtypes, respectively. In univariable analysis, PIK3CA mutations were associated with better IDFS (HR, 0.77; 95% CI, 0.71 to 0.84; P, .001), with evidence for a stronger effect in the first years of follow-up (0 to 5 years: HR, 0.73; 95% CI, 0.66 to 0.81; P, .001; 5 to 10 years: HR, 0.82; 95% CI, 0.68 to 0.99; P = .037); . 10 years: (HR, 1.15; 95% CI, 0.84 to 1.58; P = .38; P heterogeneity = .02). In multivariable analysis, PIK3CA genotype remained significant for improved IDFS (P = .043), but not for the DDFS and OS end points. Conclusion In this large pooled analysis, PIK3CA mutations were significantly associated with a better IDFS, DDFS, and OS, but had a lesser prognostic effect after adjustment for other prognostic factors.

Details

Authors
  • Dimitrios Zardavas
  • Luc Te Marvelde
  • Roger L. Milne
  • Debora Fumagalli
  • George Fountzilas
  • Vassiliki Kotoula
  • Evangelia Razis
  • George Papaxoinis
  • Heikki Joensuu
  • Mary Ellen Moynahan
  • Bryan T. Hennessy
  • Ivan Bieche
  • Olle Stal
  • Barry Iacopetta
  • Jeanette Dupont Jensen
  • Sandra O'Toole
  • Elena Lopez-Knowles
  • Mattia Barbaraeschi
  • Shinzaburo Noguchi
  • Hatem A. Azim
  • Enrique Lerma
  • Thomas Bachelot
  • Qing Wang
  • Gizeh Perez-Tenorio
  • Cornelis J.H. Can De Velde
  • Daniel W. Rea
  • Vicky Sabine
  • John M.S. Bartlett
  • Christos Sotiriou
  • Stefan Michiels
  • Sherene Loi
Organisations
External organisations
  • Breast International Group
  • Cancer Council
  • Aristotle University of Thessaloniki
  • Hygeia Hospital
  • Hippokration Hospital
  • Helsinki University Central Hospital
  • Memorial Sloan-Kettering Cancer Center
  • Beaumont Hospital, Dublin
  • Curie Institute, Paris
  • Linköping University
  • University of Western Australia, Crawley
  • University of Southern Denmark
  • Garvan Institute of Medical Research
  • Institute of Cancer Research London
  • Santa Chiara Hospital, Trento
  • Osaka University
  • American University of Beirut
  • Autonomous University of Barcelona
  • Centre de Recherche en Cancérologie de Lyon
  • Leiden University Medical Centre
  • University of Birmingham
  • University of Guelph
  • Ontario Institute for Cancer Research
  • Free University of Brussels (ULB)
  • University of Paris-Sud
  • University of Melbourne
  • University of Helsinki
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)981-990
Number of pages10
JournalJournal of Clinical Oncology
Volume36
Issue number10
Publication statusPublished - 2018 Jan 1
Publication categoryResearch
Peer-reviewedYes