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dc.contributor.authorZardavas, D
dc.contributor.authorTe Marvelde, L
dc.contributor.authorMilne, RL
dc.contributor.authorFumagalli, D
dc.contributor.authorFountzilas, G
dc.contributor.authorKotoula, V
dc.contributor.authorRazis, E
dc.contributor.authorPapaxoinis, G
dc.contributor.authorJoensuu, H
dc.contributor.authorMoynahan, ME
dc.contributor.authorHennessy, BT
dc.contributor.authorBieche, I
dc.contributor.authorSaal, LH
dc.contributor.authorStal, O
dc.contributor.authorIacopetta, B
dc.contributor.authorJensen, JD
dc.contributor.authorO'Toole, S
dc.contributor.authorLopez-Knowles, E
dc.contributor.authorBarbaraeschi, M
dc.contributor.authorNoguchi, S
dc.contributor.authorAzim, HA
dc.contributor.authorLerma, E
dc.contributor.authorBachelot, T
dc.contributor.authorWang, Q
dc.contributor.authorPerez-Tenorio, G
dc.contributor.authorCan de Velde, CJH
dc.contributor.authorRea, DW
dc.contributor.authorSabine, V
dc.contributor.authorBartlett, JMS
dc.contributor.authorSotiriou, C
dc.contributor.authorMichiels, S
dc.contributor.authorLoi, S
dc.coverage.spatialUnited States
dc.date.accessioned2022-08-16T13:24:45Z
dc.date.available2022-08-16T13:24:45Z
dc.date.issued2018-04-01
dc.identifier.citationJournal of Clinical Oncology, 2018, 36 (10), pp. 981 - 990en_US
dc.identifier.issn0732-183X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5273
dc.identifier.eissn1527-7755
dc.identifier.eissn1527-7755
dc.identifier.doi10.1200/JCO.2017.74.8301
dc.description.abstractPurpose 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.
dc.formatPrint-Electronic
dc.format.extent981 - 990
dc.languageeng
dc.language.isoengen_US
dc.publisherAMER SOC CLINICAL ONCOLOGYen_US
dc.relation.ispartofJournal of Clinical Oncology
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectAdolescent
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectBreast Neoplasms
dc.subjectClass I Phosphatidylinositol 3-Kinases
dc.subjectDisease-Free Survival
dc.subjectFemale
dc.subjectGenotype
dc.subjectHumans
dc.subjectMiddle Aged
dc.subjectMutation
dc.subjectNeoplasm Staging
dc.subjectPrognosis
dc.subjectProportional Hazards Models
dc.subjectReceptor, ErbB-2
dc.subjectReceptors, Estrogen
dc.subjectSurvival Rate
dc.subjectYoung Adult
dc.titleTumor PIK3CA Genotype and Prognosis in Early-Stage Breast Cancer: A Pooled Analysis of Individual Patient Data.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-04-01
dc.date.updated2022-08-16T12:54:22Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1200/JCO.2017.74.8301en_US
rioxxterms.licenseref.startdate2018-04-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/29470143
pubs.issue10
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology
pubs.publication-statusPublished
pubs.volume36
icr.researchteamMolecular Oncologyen_US
dc.contributor.icrauthorLopez Knowles, Elena
icr.provenanceDeposited by Dr Elena Lopez Knowles on 2022-08-16. Deposit type is initial. No. of files: 1. Files: jco.2017.74.8301.pdf


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