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dc.contributor.authorHeindl, Aen_US
dc.contributor.authorSestak, Ien_US
dc.contributor.authorNaidoo, Ken_US
dc.contributor.authorCuzick, Jen_US
dc.contributor.authorDowsett, Men_US
dc.contributor.authorYuan, Yen_US
dc.date.accessioned2017-11-03T10:45:00Z
dc.date.available2017-06-05en_US
dc.date.issued2018-02-01en_US
dc.date.submitted2017-10-24T12:02:16.290Z
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/28597
dc.description.abstractBackground: Despite increasing evidence supporting the clinical utility of immune infiltration in the estrogen receptor-negative (ER-) subtype, the prognostic value of immune infiltration for ER+ disease is not well defined. Methods: Quantitative immune scores of cell abundance and spatial heterogeneity were computed using a fully automated hematoxylin and eosin-stained image analysis algorithm and spatial statistics for 1178 postmenopausal patients with ER+ breast cancer treated with five years' tamoxifen or anastrozole. The prognostic significance of immune scores was compared with Oncotype DX 21-gene recurrence score (RS), PAM50 risk of recurrence (ROR) score, IHC4, and clinical treatment score, available for 963 patients. Statistical tests were two-sided. Results: Scores of immune cell abundance were not associated with recurrence-free survival. In contrast, high immune spatial scores indicating increased cell spatial clustering were associated with poor 10-year, early (0-5 years), and late (5-10 years) recurrence-free survival (Immune Hotspot: LR-χ2 = 14.06, P < .001, for 0-10 years; LR-χ2 = 6.24, P = .01, for 0-5 years; LR-χ2 = 7.89, P = .005, for 5-10 years). The prognostic value of spatial scores for late recurrence was similar to that of IHC4 and RS in both populations, but was not as strong as other tests in comparison for recurrence across 10 years. Conclusions: These results provide a missing link between tumor immunity and disease outcome in ER+ disease by examining tumor spatial architecture. The association between spatial scores and late recurrence suggests a lasting memory of protumor immunity that may impact disease progression and evolution of endocrine treatment resistance, which may be exploited for therapeutic advances.en_US
dc.description.sponsorshipThis work was supported by the Royal Marsden National Institutes of Health Biomedical Research Centre grant A105. MD and YY acknowledge support by the Royal Marsden National Institutes of Health Biomedical Research Centre. MD acknowledges a Breast Cancer Now grant (CTR-Q4-Y1). JC and IS acknowledge a CRUK grant (C569/A16891). YY acknowledges support by CRUK (C45982/A21808), Breast Cancer Now (2015NovPR638) and the Wellcome Trust (105104/Z/14/Z).en_US
dc.languageengen_US
dc.relation.ispartofJ Natl Cancer Insten_US
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.subjectAgeden_US
dc.subjectAnastrozoleen_US
dc.subjectAntineoplastic Agentsen_US
dc.subjectBiomarkers, Tumoren_US
dc.subjectBreast Neoplasmsen_US
dc.subjectDisease-Free Survivalen_US
dc.subjectFemaleen_US
dc.subjectHumansen_US
dc.subjectLymphocyte Counten_US
dc.subjectLymphocytes, Tumor-Infiltratingen_US
dc.subjectMiddle Ageden_US
dc.subjectNeoplasm Recurrence, Localen_US
dc.subjectNitrilesen_US
dc.subjectReceptors, Estrogenen_US
dc.subjectRisk Factorsen_US
dc.subjectTamoxifenen_US
dc.subjectTriazolesen_US
dc.titleRelevance of Spatial Heterogeneity of Immune Infiltration for Predicting Risk of Recurrence After Endocrine Therapy of ER+ Breast Cancer.en_US
dc.typeArticle
dc.rights.holder© The Author 2017. Published by Oxford University Press.
dc.identifier.doi10.1093/jnci/djx137en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/28859291en_US
pubs.issue2en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume110en_US
dcterms.dateAccepted2017-06-05en_US


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