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Racial differences in breast cancer outcomes by hepatocyte growth factor pathway expression

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Purpose

Black women have a 40% increased risk of breast cancer-related mortality. These outcome disparities may reflect differences in tumor pathways and a lack of targetable therapies for specific subtypes that are more common in Black women. Hepatocyte growth factor (HGF) is a targetable pathway that promotes breast cancer tumorigenesis, is associated with basal-like breast cancer, and is differentially expressed by race. This study assessed whether a 38-gene HGF expression signature is associated with recurrence and survival in Black and non-Black women.

Methods

Study participants included 1957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n = 1251, 171 recurrences), overall, and breast cancer-specific mortality (n = 706, 190/328 breast cancer/overall deaths) using Cox proportional hazard models.

Results

Women with HGF-positive tumors had higher recurrence rates [HR 1.88, 95% CI (1.19, 2.98)], breast cancer-specific mortality [HR 1.90, 95% CI (1.26, 2.85)], and overall mortality [HR 1.69; 95% CI (1.17, 2.43)]. Among Black women, HGF positivity was significantly associated with higher 5-year rate of recurrence [HR 1.73; 95% CI (1.01, 2.99)], but this association was not significant in non-Black women [HR 1.68; 95% CI (0.72, 3.90)]. Among Black women, HGF-positive tumors had elevated breast cancer-specific mortality [HR 1.80, 95% CI (1.05, 3.09)], which was not significant in non-Black women [HR 1.52; 95% CI (0.78, 2.99)].

Conclusion

This multi-gene HGF signature is a poor-prognosis feature for breast cancer and may identify patients who could benefit from HGF-targeted treatments, an unmet need for Black and triple-negative patients.

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Data availability

The datasets generated during the current study are available from the corresponding author upon reasonable request. The code in this study is available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to acknowledge and thank all the patients and families of the Carolina Breast Cancer Study for their contributions to this work. We are indebted for their participation in bringing this study into fruition.

Funding

Gieira Jones was supported by the UNC Lineberger Cancer Control Education Program (T32CA057726). This research was supported by a Grant from UNC Lineberger Comprehensive Cancer Center, which is funded by the University Cancer Research Fund of North Carolina, the Susan B Komen Foundation (OGUNC1202), the National Cancer Institute of the National Institutes of Health (P01CA151135), the National Cancer Institute (U54 CA156733), and the National Cancer Institute Specialized Program of Research Excellence (SPORE) in Breast Cancer (NIH/NCI P50-CA58223).

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Authors and Affiliations

  1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, 253 Rosenau Hall, CB #7435, 135 Dauer Drive, Chapel Hill, NC, 27599-7400, USA

    Gieira S. Jones, Halei Benefield, Linnea T. Olsson, Erin L. Kirk, Hazel B. Nichols, Andrew F. Olshan & Melissa A. Troester

  2. Department of Genetics, University of North Carolina-Chapel Hill-Chapel Hill, Chapel Hill, USA

    Katherine A. Hoadley & Michael I. Love

  3. Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA

    Katherine A. Hoadley, Heather J. Tipaldos, Jodie M. Fleming, Michael I. Love, Hazel B. Nichols, Andrew F. Olshan & Melissa A. Troester

  4. Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, USA

    Alina M. Hamilton

  5. Department of Biostatistics, University of North Carolina-Chapel Hill, Chapel Hill, USA

    Arjun Bhattacharya & Michael I. Love

  6. Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA

    Arjun Bhattacharya

  7. Institute for Quantitative and Computational Biosciences, David Geffen School of Medicine, University of California, Los Angeles, USA

    Arjun Bhattacharya

  8. Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, USA

    Jodie M. Fleming

  9. Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, USA

    Kevin P. Williams

  10. Department of Pharmaceutical Sciences, North Carolina Central University, Durham, USA

    Kevin P. Williams

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  1. Gieira S. Jones
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  14. Melissa A. Troester
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Corresponding author

Correspondence to Melissa A. Troester.

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Conflict of interest

The University of North Carolina is an interest owner in University Genomics, the patent holder of the PAM50 assay.

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Jones, G.S., Hoadley, K.A., Benefield, H. et al. Racial differences in breast cancer outcomes by hepatocyte growth factor pathway expression. Breast Cancer Res Treat 192, 447–455 (2022). https://doi.org/10.1007/s10549-021-06497-w

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  • DOI: https://doi.org/10.1007/s10549-021-06497-w

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