TY - JOUR
T1 - Tumor PIK3CA genotype and prognosis in early-stage breast cancer:
T2 - A pooled analysis of individual patient data
AU - Zardavas, Dimitrios
AU - Te Marvelde, Luc
AU - Milne, Roger L.
AU - Fumagalli, Debora
AU - Fountzilas, George
AU - Kotoula, Vassiliki
AU - Razis, Evangelia
AU - Papaxoinis, George
AU - Joensuu, Heikki
AU - Moynahan, Mary Ellen
AU - Hennessy, Bryan T.
AU - Bieche, Ivan
AU - Saal, Lao H.
AU - Stal, Olle
AU - Iacopetta, Barry
AU - Jensen, Jeanette Dupont
AU - O'Toole, Sandra
AU - Lopez-Knowles, Elena
AU - Barbaraeschi, Mattia
AU - Noguchi, Shinzaburo
AU - Azim, Hatem A.
AU - Lerma, Enrique
AU - Bachelot, Thomas
AU - Wang, Qing
AU - Perez-Tenorio, Gizeh
AU - Can De Velde, Cornelis J.H.
AU - Rea, Daniel
AU - Sabine, Vicky
AU - Bartlett, John M.S.
AU - Sotiriou, Christos
AU - Michiels, Stefan
AU - Loi, Sherene
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85045022030&partnerID=8YFLogxK
U2 - 10.1200/JCO.2017.74.8301
DO - 10.1200/JCO.2017.74.8301
M3 - Article
AN - SCOPUS:85045022030
SN - 0732-183X
VL - 36
SP - 981
EP - 990
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 10
ER -
