Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

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dc.citation.issue10
dc.citation.volume7
dc.contributor.authorThomas A
dc.contributor.authorRouth ED
dc.contributor.authorPullikuth A
dc.contributor.authorJin G
dc.contributor.authorSu J
dc.contributor.authorChou JW
dc.contributor.authorHoadley KA
dc.contributor.authorPrint C
dc.contributor.authorKnowlton N
dc.contributor.authorBlack MA
dc.contributor.authorDemaria S
dc.contributor.authorWang E
dc.contributor.authorBedognetti D
dc.contributor.authorJones WD
dc.contributor.authorMehta GA
dc.contributor.authorGatza ML
dc.contributor.authorPerou CM
dc.contributor.authorPage DB
dc.contributor.authorTriozzi P
dc.contributor.authorMiller LD
dc.coverage.spatialUnited States
dc.date.accessioned2025-03-19T01:19:05Z
dc.date.available2025-03-19T01:19:05Z
dc.date.issued2018-07-30
dc.description.abstractMounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). Tumor immune subclasses were associated with survival in patients with high TMB (TMB-Hi, P < 0.001) but not in those with low TMB (TMB-Lo, P = 0.44). This statistical relationship was confirmed in the METABRIC cohort (TMB-Hi, P = 0.047; TMB-Lo, P = 0.39), and also found to hold true in the more-indolent Luminal A tumor subtype (TMB-Hi, P = 0.011; TMB-Lo, P = 0.91). In TMB-Hi tumors, the FID subclass was associated with prolonged survival independent of tumor stage, molecular subtype, age and treatment. Copy number analysis revealed the reproducible, preferential amplification of chromosome 1q immune-regulatory genes in the PID immune subclass. These findings demonstrate a previously unappreciated role for TMB as a determinant of immune-mediated survival of breast cancer patients and identify candidate immune-regulatory mechanisms associated with immunologically cold tumors. Immune subtyping of breast cancers may offer opportunities for therapeutic stratification.
dc.description.confidentialfalse
dc.format.paginatione1490854-
dc.identifier.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/30386679
dc.identifier.citationThomas A, Routh ED, Pullikuth A, Jin G, Su J, Chou JW, Hoadley KA, Print C, Knowlton N, Black MA, Demaria S, Wang E, Bedognetti D, Jones WD, Mehta GA, Gatza ML, Perou CM, Page DB, Triozzi P, Miller LD. (2018). Tumor mutational burden is a determinant of immune-mediated survival in breast cancer.. Oncoimmunology. 7. 10. (pp. e1490854-).
dc.identifier.doi10.1080/2162402X.2018.1490854
dc.identifier.eissn2162-402X
dc.identifier.elements-typejournal-article
dc.identifier.issn2162-4011
dc.identifier.numbere1490854
dc.identifier.pii1490854
dc.identifier.urihttps://mro.massey.ac.nz/handle/10179/72674
dc.languageeng
dc.publisherTaylor and Francis, England
dc.relation.isPartOfOncoimmunology
dc.rights(c) 2018 The Author/s
dc.rightsCC BY-NC-ND 4.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/deed.en
dc.subjectbreast cancer
dc.subjectimmune subtypes
dc.subjectmutational burden
dc.subjectprognosis
dc.subjectsurvival
dc.titleTumor mutational burden is a determinant of immune-mediated survival in breast cancer
dc.typeJournal article
pubs.elements-id500041
pubs.organisational-groupOther
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