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

Gieira S Jones¹, Katherine A Hoadley^{2

3}, Halei Benefield¹, Linnea T Olsson¹, Alina M Hamilton⁴, Arjun Bhattacharya^{5

6

7}, Erin L Kirk¹, Heather J Tipaldos³, Jodie M Fleming^{3

8}, Kevin P Williams^{9

10}, Michael I Love^{2

3

5}, Hazel B Nichols^{1

3}, Andrew F Olshan^{1

3}, Melissa A Troester^{11

12}

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.
² Department of Genetics, University of North Carolina-Chapel Hill-Chapel Hill, Chapel Hill, USA.
³ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
⁴ Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, USA.
⁵ Department of Biostatistics, University of North Carolina-Chapel Hill, Chapel Hill, USA.
⁶ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
⁷ Institute for Quantitative and Computational Biosciences, David Geffen School of Medicine, University of California, Los Angeles, USA.
⁸ Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, USA.
⁹ Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, USA.
¹⁰ Department of Pharmaceutical Sciences, North Carolina Central University, Durham, USA.
¹¹ 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. troester@email.unc.edu.
¹² Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA. troester@email.unc.edu.

PMID: 35034243
PMCID: PMC9380654
DOI: 10.1007/s10549-021-06497-w

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

Gieira S Jones et al. Breast Cancer Res Treat. 2022 Apr.

. 2022 Apr;192(2):447-455.

doi: 10.1007/s10549-021-06497-w. Epub 2022 Jan 16.

Authors

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.
² Department of Genetics, University of North Carolina-Chapel Hill-Chapel Hill, Chapel Hill, USA.
³ Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
⁴ Department of Pathology and Laboratory Medicine, University of North Carolina-Chapel Hill, Chapel Hill, USA.
⁵ Department of Biostatistics, University of North Carolina-Chapel Hill, Chapel Hill, USA.
⁶ Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, USA.
⁷ Institute for Quantitative and Computational Biosciences, David Geffen School of Medicine, University of California, Los Angeles, USA.
⁸ Department of Biological and Biomedical Sciences, North Carolina Central University, Durham, USA.
⁹ Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, USA.
¹⁰ Department of Pharmaceutical Sciences, North Carolina Central University, Durham, USA.
¹¹ 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. troester@email.unc.edu.
¹² Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA. troester@email.unc.edu.

PMID: 35034243
PMCID: PMC9380654
DOI: 10.1007/s10549-021-06497-w

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.

Keywords: Breast cancer; Hepatocyte growth factor.

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Conflict of interest statement

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

Figures

**Fig 1. Kaplan Meier Plot of HGF association with survival outcomes in Carolina Breast Cancer Study.**
Panel A- disease-free survival (CBCS-3), Panel B- breast cancer specific survival (CBCS-1/2), Panel C- overall survival (CBCS-1/2).

See this image and copyright information in PMC

References

1. American Cancer Society. Breast Cancer Facts & Figures 2019–2020. Am Cancer Soc 2019;
1. Benefield HC, Allott EH, Reeder-Hayes KE, Perou CM, Carey LA, Geradts J, et al. Borderline Estrogen Receptor–Positive Breast Cancers in Black and White Women. JNCI J Natl Cancer Inst 2019; - PMC - PubMed
1. Collin LJ, Yan M, Jiang R, Ward KC, Crawford B, Torres MA, et al. Oncotype DX recurrence score implications for disparities in chemotherapy and breast cancer mortality in Georgia. npj Breast Cancer 2019; - PMC - PubMed
1. Pastoriza JM, Karagiannis GS, Lin J, Lanjewar S, Entenberg D, Condeelis JS, et al. Black race and distant recurrence after neoadjuvant or adjuvant chemotherapy in breast cancer. Clin Exp Metastasis 2018; - PMC - PubMed
1. Kabat GC, Ginsberg M, Sparano JA, Rohan TE. Risk of Recurrence and Mortality in a Multi-Ethnic Breast Cancer Population. J Racial Ethn Heal Disparities 2017; - PubMed

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

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

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