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Hepatocyte Growth Factor Pathway Expression in Breast Cancer by Race and Subtype

Citation

Jones, Gieira S.; Hoadley, Katherine A.; Olsson, Linnea T.; Hamilton, Alina M.; Bhattacharya, Arjun; Kirk, Erin L.; Tipaldos, Heather J.; Fleming, Jodie M.; Love, Michael I.; & Nichols, Hazel B., et al. (2021). Hepatocyte Growth Factor Pathway Expression in Breast Cancer by Race and Subtype. Breast Cancer Research, 23(1), 80. PMCID: PMC8336233

Abstract

BACKGROUND: African American women have the highest risk of breast cancer mortality compared to other racial groups. Differences in tumor characteristics have been implicated as a possible cause; however, the tumor microenvironment may also contribute to this disparity in mortality. Hepatocyte growth factor (HGF) is a stroma-derived marker of the tumor microenvironment that may affect tumor progression differentially by race.
OBJECTIVE: To examine whether an HGF gene expression signature is differentially expressed by race and tumor characteristics.
METHODS: Invasive breast tumors from 1957 patients were assessed for a 38-gene RNA-based HGF gene expression signature. Participants were black (n = 1033) and non-black (n = 924) women from the population-based Carolina Breast Cancer Study (1993-2013). Generalized linear models were used to estimate the relative frequency differences (RFD) in HGF status by race, clinical, and demographic factors.
RESULTS: Thirty-two percent of tumors were positive for the HGF signature. Black women were more likely [42% vs. 21%; RFD = + 19.93% (95% CI 16.00, 23.87)] to have HGF-positive tumors compared to non-black women. Triple-negative patients had a higher frequency of HGF positivity [82% vs. 13% in non-triple-negative; RFD = + 65.85% (95% CI 61.71, 69.98)], and HGF positivity was a defining feature of basal-like subtype [92% vs. 8% in non-basal; RFD = + 81.84% (95% CI 78.84, 84.83)]. HGF positivity was associated with younger age, stage, higher grade, and high genomic risk of recurrence (ROR-PT) score.
CONCLUSION: HGF expression is a defining feature of basal-like tumors, and its association with black race and young women suggests it may be a candidate pathway for understanding breast cancer disparities.

URL

http://dx.doi.org/10.1186/s13058-021-01460-5

Reference Type

Journal Article

Year Published

2021

Journal Title

Breast Cancer Research

Author(s)

Jones, Gieira S.
Hoadley, Katherine A.
Olsson, Linnea T.
Hamilton, Alina M.
Bhattacharya, Arjun
Kirk, Erin L.
Tipaldos, Heather J.
Fleming, Jodie M.
Love, Michael I.
Nichols, Hazel B.
Olshan, Andrew F.
Troester, Melissa A.

Article Type

Regular

PMCID

PMC8336233

Data Set/Study

Carolina Breast Cancer Study (CBCS)

Continent/Country

United States of America

State

North Carolina

Sex/Gender

Ciswomen

ORCiD

Olshan - 0000-0001-9115-5128