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

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 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 1,957 invasive breast cancer cases from the Carolina Breast Cancer Study. The HGF signature was evaluated in association with recurrence (n=1,251, 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.