Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women

PURPOSE: African-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltratio...

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Authors: O’Meara, Tess, Safonov, Anton, Casadevall Aguilar, David, Qing, Tao, Silber, Andrea, Killelea, Brigid, Hatzis, Christos, Pusztai, Lajos
Format: article
Status:Versión aceptada para publicación
Publication Date:2019
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/42900
Online Access:http://hdl.handle.net/10230/42900
http://dx.doi.org/10.1007/s10549-019-05156-5
Access Level:Open access
Keyword:Genetics
Immune microenvironment
Immunotherapy
Race
Triple-negative breast cancer
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spelling Immune microenvironment of triple-negative breast cancer in African-American and Caucasian womenO’Meara, TessSafonov, AntonCasadevall Aguilar, DavidQing, TaoSilber, AndreaKillelea, BrigidHatzis, ChristosPusztai, LajosGeneticsImmune microenvironmentImmunotherapyRaceTriple-negative breast cancerPURPOSE: African-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltration is the most consistent predictive marker for chemotherapy response and improved prognosis in TNBC. In this study, we test the hypothesis that the immune microenvironment differs between AA and Caucasian patients. METHODS: RNA-seq expression data were obtained from The Cancer Genome Atlas (TCGA) database for 162 AA and 697 Caucasian breast cancers. Estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-positive, and TNBC subtypes were included in the analyses. Tumor infiltrating lymphocyte (TIL) counts, immunomodulatory scores, and molecular subtypes were obtained from prior publications for a subset of the TNBC cases. Differences in immune cell distributions and immune functions, measured through gene expression and TIL counts, as well as neoantigen, somatic mutation, amplification, and deletion loads, were compared by race and tumor subtype. RESULTS: Immune metagene analysis demonstrated marginal immune attenuation in AA TNBC relative to Caucasian TNBC that did not reach statistical significance. The distributions of immune cell populations, lymphocyte infiltration, molecular subtypes, and genomic aberrations between AA and Caucasian subtypes were also not significantly different. The MHC1 metagene demonstrated increased expression in AA ER-positive cancers relative to Caucasian ER-positive cancers. CONCLUSIONS: This study suggests that the immunological differences between AA and Caucasian breast cancers represented by TCGA data are subtle, if they exist at all. We observed no consistent racial differences in immune gene expression or TIL counts in TNBC by race. However, this study cannot rule out small differences in immune cell subtype distribution and activity status that may not be apparent in bulk RNA analysis.Springer20192019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/42900http://dx.doi.org/10.1007/s10549-019-05156-5reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)Inglés© Springer The final publication is available at Springer via http://dx.doi.org/10.1007/s10549-019-05156-5info:eu-repo/semantics/openAccessoai:recercat.cat:10230/429002026-05-29T05:05:01Z
dc.title.none.fl_str_mv Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
title Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
spellingShingle Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
O’Meara, Tess
Genetics
Immune microenvironment
Immunotherapy
Race
Triple-negative breast cancer
title_short Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
title_full Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
title_fullStr Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
title_full_unstemmed Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
title_sort Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
dc.creator.none.fl_str_mv O’Meara, Tess
Safonov, Anton
Casadevall Aguilar, David
Qing, Tao
Silber, Andrea
Killelea, Brigid
Hatzis, Christos
Pusztai, Lajos
author O’Meara, Tess
author_facet O’Meara, Tess
Safonov, Anton
Casadevall Aguilar, David
Qing, Tao
Silber, Andrea
Killelea, Brigid
Hatzis, Christos
Pusztai, Lajos
author_role author
author2 Safonov, Anton
Casadevall Aguilar, David
Qing, Tao
Silber, Andrea
Killelea, Brigid
Hatzis, Christos
Pusztai, Lajos
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Genetics
Immune microenvironment
Immunotherapy
Race
Triple-negative breast cancer
topic Genetics
Immune microenvironment
Immunotherapy
Race
Triple-negative breast cancer
description PURPOSE: African-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltration is the most consistent predictive marker for chemotherapy response and improved prognosis in TNBC. In this study, we test the hypothesis that the immune microenvironment differs between AA and Caucasian patients. METHODS: RNA-seq expression data were obtained from The Cancer Genome Atlas (TCGA) database for 162 AA and 697 Caucasian breast cancers. Estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-positive, and TNBC subtypes were included in the analyses. Tumor infiltrating lymphocyte (TIL) counts, immunomodulatory scores, and molecular subtypes were obtained from prior publications for a subset of the TNBC cases. Differences in immune cell distributions and immune functions, measured through gene expression and TIL counts, as well as neoantigen, somatic mutation, amplification, and deletion loads, were compared by race and tumor subtype. RESULTS: Immune metagene analysis demonstrated marginal immune attenuation in AA TNBC relative to Caucasian TNBC that did not reach statistical significance. The distributions of immune cell populations, lymphocyte infiltration, molecular subtypes, and genomic aberrations between AA and Caucasian subtypes were also not significantly different. The MHC1 metagene demonstrated increased expression in AA ER-positive cancers relative to Caucasian ER-positive cancers. CONCLUSIONS: This study suggests that the immunological differences between AA and Caucasian breast cancers represented by TCGA data are subtle, if they exist at all. We observed no consistent racial differences in immune gene expression or TIL counts in TNBC by race. However, this study cannot rule out small differences in immune cell subtype distribution and activity status that may not be apparent in bulk RNA analysis.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/42900
http://dx.doi.org/10.1007/s10549-019-05156-5
url http://hdl.handle.net/10230/42900
http://dx.doi.org/10.1007/s10549-019-05156-5
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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