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

  • Tess O’Meara
  • Anton Safonov
  • David Casadevall
  • Tao Qing
  • Andrea Silber
  • Brigid Killelea
  • Christos Hatzis
  • Lajos PusztaiEmail author
Epidemiology
  • 51 Downloads

Abstract

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.

Keywords

Triple-negative breast cancer Race Immune microenvironment Immunotherapy Genetics 

Notes

Funding

This research was supported by an NCI R01 Grant (R01CA219647) to L.P.

Compliance with ethical standards

Conflict of interest

Tess O’Meara, Anton Safonov, David Casadevall, Tao Qing, Brigid Killelea declares they have no conflict of interest. Andrea Silber has received remuneration from Astra Zeneca. Christos Hatzis is now an employee of Bristol-Myers Squibb Co. Lajos Pusztai has received consulting fees and honoraria from Merck, Astra Zeneca, Novartis, Seattle Genetics, Pfizer, and Almac.

Ethical approval

This article does not contain studies with human participants or animals performed by any of the authors.

Informed consent

No informed consent was needed for this study. Human subjects were not involved.

Supplementary material

10549_2019_5156_MOESM1_ESM.xlsx (40 kb)
Supplementary material 1 Supplementary Table 1. Gene members and expression data availability for immune gene expression measures. (XLSX 39 KB)
10549_2019_5156_MOESM2_ESM.xlsx (32 kb)
Supplementary material 2 Supplementary Table 2. Number of available cases for gene expression, TIL, and genomic analyses. (XLSX 31 KB)
10549_2019_5156_MOESM3_ESM.xlsx (44 kb)
Supplementary material 3 Supplementary Table 3. Statistical analyses of metagene expression and genomic metrics by race and tumor subtype. (XLSX 44 KB)
10549_2019_5156_MOESM4_ESM.xlsx (111 kb)
Supplementary material 4 Supplementary Table 4. Differentially expressed immune genes between AA and Caucasian breast cancer subtypes. (XLSX 111 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Breast Medical Oncology, Yale School of MedicineYale Cancer CenterNew HavenUSA
  2. 2.University of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Institut Hospital del Mar d’Investigacions Mèdiques (IMIM)BarcelonaSpain

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