Impact of Ethnic Differences and HER2 Protein Expression on the Age at Breast Cancer Diagnosis: A Mixed Methods Study

Purpose: Despite advances in breast cancer (BC) research, a significant research gap remains in understanding the interplay of ethnicity, Human Epidermal Growth Factor Receptor 2 (HER2) protein expression and age at BC diagnosis, particularly in underrepresented minority populations from Africa. We analyzed variations in HER2 protein expression and ethnic differences in age at BC diagnosis across indigenous Namibian and American women diagnosed with BC. Methods: Using a mixed methods study, we analyzed case series cohort from 1,953 women all diagnosed with invasive BC, including 98 indigenous Namibian women and 1855 American women retrieved from the cBioPortal database. HER2 positivity rate was obtained by staining breast tissue biopsies and quantifying HER2 protein expression, with this study accessing the data retrospectively. We stratified participants by ethnicity and compared age at BC diagnosis and HER2 status to elucidate disparities. Chi-square test for proportions, t-test for independence and the cumulative probability analysis curves were used for statistical analysis. A p-value of <0.05 was considered significant. Results: Indigenous Namibian women were diagnosed with BC significantly with a younger age compared to American women (White, p<0.0001, and African American p=0.0035). In a logistic regression analysis, African American women with BC had significantly lower odds of HER2-positive status compared to White women (OR = 0.52, p < 0.001). The cumulative probability analysis further delineated the probabilities for age at BC diagnosis according to ethnic disparities with indigenous Namibian, Asian, and African American women showing significant higher probabilities for younger ages at BC diagnosis compared to White women (p<0.0001, p=0.0035, and p=0.0057, respectively). Conclusion: Ethnic disparities and the variations in HER2 protein expression and age at BC diagnosis between indigenous Namibian and American women diagnosed with BC necessitate tailored population genetics and geographical differences in BC screening approach to address global BC screening equity.