dc.contributor.author | Prat, A | |
dc.contributor.author | Cheang, MCU | |
dc.contributor.author | Galván, P | |
dc.contributor.author | Nuciforo, P | |
dc.contributor.author | Paré, L | |
dc.contributor.author | Adamo, B | |
dc.contributor.author | Muñoz, M | |
dc.contributor.author | Viladot, M | |
dc.contributor.author | Press, MF | |
dc.contributor.author | Gagnon, R | |
dc.contributor.author | Ellis, C | |
dc.contributor.author | Johnston, S | |
dc.date.accessioned | 2016-12-23T10:46:18Z | |
dc.date.issued | 2016-10-01 | |
dc.identifier.citation | JAMA oncology, 2016, 2 (10), pp. 1287 - 1294 | |
dc.identifier.issn | 2374-2437 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/346 | |
dc.identifier.eissn | 2374-2445 | |
dc.identifier.doi | 10.1001/jamaoncol.2016.0922 | |
dc.description.abstract | IMPORTANCE: 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.format | Print | |
dc.format.extent | 1287 - 1294 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER MEDICAL ASSOC | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Bone Neoplasms | |
dc.subject | Breast Neoplasms | |
dc.subject | Nitriles | |
dc.subject | Triazoles | |
dc.subject | Quinazolines | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Prognosis | |
dc.subject | Disease-Free Survival | |
dc.subject | Treatment Outcome | |
dc.subject | Proportional Hazards Models | |
dc.subject | Retrospective Studies | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Letrozole | |
dc.subject | Lapatinib | |
dc.title | Prognostic Value of Intrinsic Subtypes in Hormone Receptor-Positive Metastatic Breast Cancer Treated With Letrozole With or Without Lapatinib. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2016-03-13 | |
rioxxterms.versionofrecord | 10.1001/jamaoncol.2016.0922 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2016-10 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | JAMA oncology | |
pubs.issue | 10 | |
pubs.notes | No 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-status | Published | |
pubs.volume | 2 | |
pubs.embargo.terms | No embargo | |
icr.researchteam | Endocrine Therapy Resistance | |
icr.researchteam | Genomic Analysis – Clinical Trials | |
dc.contributor.icrauthor | Cheang, Chon | |