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.

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 basallike 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.

Purpose of Review-To review research on breast cancer mortality disparities, emphasizing research conducted in the Carolina Breast Cancer Study, with a focus on challenges and opportunities for integration of tumor biology and access characteristics across the cancer care continuum.Recent Findings-Black women experience higher mortality following breast cancer diagnosis, despite lower incidence compared to white women. Biological factors, such as stage at diagnosis and breast cancer subtypes, play a role in these disparities. Simultaneously, social, behavioral, environmental, and access to care factors are important. However, integrated studies of biology and access are challenging and it is uncommon to have both data types available in the same study population. The central emphasis of Phase 3 of the Carolina Breast Cancer Study, initiated in 2008, was to collect rich data on biology (including germline and tumor genomics and pathology) and health care access in a diverse study population, with the long term goal of defining intervention opportunities to reduce disparities across the cancer care continuum.Summary-Early and ongoing research from CBCS has identified important interactions between biology and access, leading to opportunities to build greater equity. However, sample size, population-specific relationships among variables, and complexities of treatment paths along the care continuum pose important research challenges. Interdisciplinary teams, including experts

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