| Literature DB >> 29470143 |
Dimitrios Zardavas1, Luc Te Marvelde1, Roger L Milne1, Debora Fumagalli1, George Fountzilas1, Vassiliki Kotoula1, Evangelia Razis1, George Papaxoinis1, Heikki Joensuu1, Mary Ellen Moynahan1, Bryan T Hennessy1, Ivan Bieche1, Lao H Saal1, Olle Stal1, Barry Iacopetta1, Jeanette Dupont Jensen1, Sandra O'Toole1, Elena Lopez-Knowles1, Mattia Barbaraeschi1, Shinzaburo Noguchi1, Hatem A Azim1, Enrique Lerma1, Thomas Bachelot1, Qing Wang1, Gizeh Perez-Tenorio1, Cornelis J H Can de Velde1, Daniel W Rea1, Vicky Sabine1, John M S Bartlett1, Christos Sotiriou1, Stefan Michiels1, Sherene Loi1.
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.Entities:
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Year: 2018 PMID： 29470143 DOI： 10.1200/JCO.2017.74.8301
Source DB: PubMed Journal: J Clin Oncol ISSN： 0732-183X Impact factor: 44.544