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Review

Immune Responses and Risk of Triple-negative Breast Cancer: Implications for Higher Rates among African American Women

Joshua W. Ogony, Derek C. Radisky, Kathryn J. Ruddy, Steven Goodison, Daniel P. Wickland, Kathleen M. Egan, Keith L. Knutson, Yan W. Asmann and Mark E. Sherman
Joshua W. Ogony
1Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida.
2Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Derek C. Radisky
2Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Kathryn J. Ruddy
3Medical Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota.
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  • ORCID record for Kathryn J. Ruddy
Steven Goodison
1Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Daniel P. Wickland
1Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Kathleen M. Egan
4Department of Epidemiology, Moffitt Cancer Center, Tampa, Florida.
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Keith L. Knutson
5Department of Immunology, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Yan W. Asmann
1Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida.
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Mark E. Sherman
1Health Sciences Research, Mayo Clinic College of Medicine, Jacksonville, Florida.
2Cancer Biology, Mayo Clinic College of Medicine, Jacksonville, Florida.
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  • For correspondence: Sherman.Mark@mayo.edu
DOI: 10.1158/1940-6207.CAPR-19-0562 Published November 2020
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Abstract

The etiology of triple-negative breast cancers (TNBC) is poorly understood. As many TNBCs develop prior to the initiation of breast cancer screening or at younger ages when the sensitivity of mammography is comparatively low, understanding the etiology of TNBCs is critical for discovering novel prevention approaches for these tumors. Furthermore, the higher incidence rate of estrogen receptor–negative breast cancers, and specifically, of TNBCs, among young African American women (AAW) versus white women is a source of racial disparities in breast cancer mortality. Whereas immune responses to TNBCs have received considerable attention in relation to prognosis and treatment, the concept that dysregulated immune responses may predispose to the development of TNBCs has received limited attention. We present evidence that dysregulated immune responses are critical in the pathogenesis of TNBCs, based on the molecular biology of the cancers and the mechanisms proposed to mediate TNBC risk factors. Furthermore, proposed risk factors for TNBC, especially childbearing without breastfeeding, high parity, and obesity, are more prevalent among AAW than white women. Limited data suggest genetic differences in immune responses by race, which favor a stronger Thr type 2 (Th2) immune response among AAW than white women. Th2 responses contribute to wound-healing processes, which are implicated in the pathogenesis of TNBCs. Accordingly, we review data on the link between immune responses and TNBC risk and consider whether the prevalence of risk factors that result in dysregulated immunity is higher among AAW than white women.

Footnotes

  • Cancer Prev Res 2020;13:901–10

  • Received December 20, 2019.
  • Revision received April 22, 2020.
  • Accepted July 28, 2020.
  • Published first August 4, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Prevention Research: 13 (11)
November 2020
Volume 13, Issue 11
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Immune Responses and Risk of Triple-negative Breast Cancer: Implications for Higher Rates among African American Women
Joshua W. Ogony, Derek C. Radisky, Kathryn J. Ruddy, Steven Goodison, Daniel P. Wickland, Kathleen M. Egan, Keith L. Knutson, Yan W. Asmann and Mark E. Sherman
Cancer Prev Res November 1 2020 (13) (11) 901-910; DOI: 10.1158/1940-6207.CAPR-19-0562

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Immune Responses and Risk of Triple-negative Breast Cancer: Implications for Higher Rates among African American Women
Joshua W. Ogony, Derek C. Radisky, Kathryn J. Ruddy, Steven Goodison, Daniel P. Wickland, Kathleen M. Egan, Keith L. Knutson, Yan W. Asmann and Mark E. Sherman
Cancer Prev Res November 1 2020 (13) (11) 901-910; DOI: 10.1158/1940-6207.CAPR-19-0562
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  • Article
    • Abstract
    • Incidence of TNBC
    • TNBC and Immune Responses in Tissues
    • TNBC Risk Factors are Associated with Deleterious Inflammation and Susceptibility to DNA Damage
    • Prevalence of Risk Factors for TNBC among AAW
    • Variation in Genetic Markers and Circulating Cytokine Levels by Race in Relation to Breast Cancer Risk
    • Proposed Model of the Immune Pathogenesis of TNBC
    • Outstanding Questions and Future Directions for Research
    • Conclusion
    • Disclosure of Potential Conflicts of Interest
    • Acknowledgments
    • Footnotes
    • References
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