Gieira S Jones1, Katherine A Hoadley2,3, Halei Benefield1, Linnea T Olsson1, Alina M Hamilton4, Arjun Bhattacharya5,6,7, Erin L Kirk1, Heather J Tipaldos3, Jodie M Fleming3,8, Kevin P Williams9,10, Michael I Love2,3,5, Hazel B Nichols1,3, Andrew F Olshan1,3, Melissa A Troester11,12. 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.
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.
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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