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dc.contributor.authorPrat, A
dc.contributor.authorCheang, MCU
dc.contributor.authorGalván, P
dc.contributor.authorNuciforo, P
dc.contributor.authorParé, L
dc.contributor.authorAdamo, B
dc.contributor.authorMuñoz, M
dc.contributor.authorViladot, M
dc.contributor.authorPress, MF
dc.contributor.authorGagnon, R
dc.contributor.authorEllis, C
dc.contributor.authorJohnston, S
dc.date.accessioned2016-12-23T10:46:18Z
dc.date.issued2016-10
dc.identifier.citationJAMA oncology, 2016, 2 (10), pp. 1287 - 1294
dc.identifier.issn2374-2437
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/346
dc.identifier.eissn2374-2445
dc.identifier.doi10.1001/jamaoncol.2016.0922
dc.description.abstractImportance The value of the intrinsic subtypes of breast cancer (luminal A, luminal B, human epidermal growth factor receptor 2 [currently known as ERBB2, but referred to as HER2 in this study]-enriched, and basal-like) in the metastatic setting is currently unknown.Objective To evaluate the association of the intrinsic subtypes of breast cancer with outcome and/or benefit in hormone receptor (HR)-positive metastatic breast cancer.Design, setting, and participants Unplanned retrospective analysis of 821 tumor samples (85.7% primary and 14.3% metastatic) from the EGF30008 phase 3 clinical trial (NCT00073528), in which postmenopausal women with HR-positive invasive breast cancer and no prior therapy for advanced or metastatic disease were randomized to letrozole with or without lapatinib, an epidermal growth factor receptor (EGFR)/HER2 tyrosine kinase inhibitor. Tumor samples were classified into each subtype using the research-based PAM50 classifier. Prior neoadjuvant/adjuvant antiestrogen therapy was allowed. Patients with extensive symptomatic visceral disease were excluded. Treatment effects were evaluated using interaction tests.Main outcomes and measures Primary and secondary end points were progression-free survival and overall survival.Results The median (range) age was 62 (31-94) years. Intrinsic subtype was the strongest prognostic factor independently associated with progression-free survival and overall survival in all patients, and in patients with HER2-negative (n = 644) or HER2-positive (n = 157) diseases. Median progression-free survival differed across the intrinsic subtypes of clinically HER2-negative disease: luminal A (16.9 [95% CI, 14.1-19.9] months), luminal B (11.0 [95% CI, 9.6-13.6] months), HER2-enriched (4.7 [95% CI, 2.7-10.8] months), and basal-like (4.1 [95% CI, 2.5-13.8] months). Median OS also differed across the intrinsic subtypes: luminal A (45 [95% CI, 41-not applicable {NA}] months), luminal B (37 [95% CI, 31-42] months), HER2-enriched (16 [95% CI, 10-NA] months), and basal-like (23 [95% CI, 12-NA] months). Patients with HER2-negative/HER2-enriched disease benefited from lapatinib therapy (median PFS, 6.49 vs 2.60 months; progression-free survival hazard ratio, 0.238 [95% CI, 0.066-0.863]; interaction P = .02).Conclusions and relevance This is the first study to reveal an association between intrinsic subtype and outcome in first-line HR-positive metastatic breast cancer. Patients with HR-positive/HER2-negative disease with a HER2-enriched profile may benefit from lapatinib in combination with endocrine therapy. The clinical value of intrinsic subtyping in hormone receptor-positive metastatic breast cancer warrants further investigation, but patients with luminal A/HER2-negative metastatic breast cancer might be good candidates for letrozole monotherapy in the first-line setting regardless of visceral disease and number of metastases.
dc.formatPrint
dc.format.extent1287 - 1294
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectHumans
dc.subjectBone Neoplasms
dc.subjectBreast Neoplasms
dc.subjectNitriles
dc.subjectTriazoles
dc.subjectQuinazolines
dc.subjectReceptor, erbB-2
dc.subjectAntineoplastic Combined Chemotherapy Protocols
dc.subjectPrognosis
dc.subjectDisease-Free Survival
dc.subjectTreatment Outcome
dc.subjectProportional Hazards Models
dc.subjectRetrospective Studies
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectKaplan-Meier Estimate
dc.subjectBiomarkers, Tumor
dc.subjectLetrozole
dc.subjectLapatinib
dc.titlePrognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib.
dc.typeJournal Article
dcterms.dateAccepted2016-03-13
rioxxterms.versionofrecord10.1001/jamaoncol.2016.0922
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-10
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfJAMA oncology
pubs.issue10
pubs.notesNo embargo
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/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
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/Endocrine Therapy Resistance
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.publication-statusPublished
pubs.volume2
pubs.embargo.termsNo embargo
icr.researchteamEndocrine Therapy Resistanceen_US
icr.researchteamGenomic Analysis – Clinical Trialsen_US
dc.contributor.icrauthorJohnston, Stephenen
dc.contributor.icrauthorCheang, Chonen


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