Abstract P5-07-02: Potential differences in stromal patterns from breast cancer metastatic lymph between South Carolina sea islander black women and white women

Abstract Breast cancer is a leading cause of death among women. Among race/ethnicities, black women have similar incidence rates but higher mortality than other races/ethnicities. Black women are diagnosed at a younger age with higher stages, grades and higher rates of lethal triple negative breast cancer. Genetic ancestry, especially West African sub-Saharan ancestry, is known to contribute to aggressive breast cancer types. In South Carolina (SC), there is a disproportionate increase in female breast cancer death rates in black women compared to white women (30.1 and 21.2/100,000 respectively for years 2000-2019). Historical accounts of the slave trade into SC report that the majority of the enslaved African originated from the West African Coast with major distributions from the sub-Saharan regions. These Africans then remained in relative isolation within communities along the south eastern coastal islands, called Sea Islands (SIs) for nearly three centuries. The geographic isolation to the SIs along the SC coast resulted in a community with a unique language, folk telling, religious beliefs and a genetically distinctive subpopulation derived largely from West African populations with low European admixture. Reasons for higher breast cancer mortality in SC black women are not understood. Contemporary literature reports that stromal collagen differences are predictive of breast cancer survival. Cell signaling changes are influenced by post translational modifications to stromal collagen, specifically hydroxylation of proline (HYP).Here, we hypothesized that collagen stroma variations between black women and white women residing in a SI zip code could part be involved in the disproportionate increase in SC black female mortality. Newly diagnosed patients were considered SI origin if both parents were from a documented SI geographic region (BW n=10; WW n=21). The study specifically evaluated collagen stromal variations in breast cancer tumor, normal adjacent tissue, normal adjacent lymph, and metastatic lymph tissue. Breast tissue microarrays (TMAs) were analyzed by tissue imaging proteomics. The collagen peptide peak intensities were analyzed using Area Under the Receiving Operating Curve and Brown/Wilson T-test p-value <0.01. Six tumor peptides were determined to be significant between the Black and White populations. These peptides were not significantly altered in normal breast tissue. Intriguingly, the largest variation when comparing by race occurred in the lymph nodes. Normal lymph tissue showed 83 significantly different collagen peptides while the metastatic lymph tissue showed significant changes in 74 collagen peptides. In both normal and metastatic lymph tissue, two out of the three most significant peptides had a higher peak intensity in the white population compared to the black population, p-value ≤0.0005. Cluster Affinity Search Technique (CAST) heat maps were used to further evaluate all peak intensities in lymph tissue. For normal lymph, a cluster of 153 peptides was found, representing 84% of total peptides. Similarly, in metastatic lymph, a cluster of 36 peptides representing 40% of total genes was reported. Certain peptides were significant in both metastatic and normal lymph tissue, whereas others were only significant in either metastatic or normal lymph. This study suggests that there may be an ancestry-dependent immune involvement to metastatic breast cancer that may contribute to the higher breast cancer mortality rates in black women from SC SI regions. More studies are warranted to investigate the contribution of collagen stroma regulation within the immune system by metastatic breast cancer. Citation Format: Ashlyn Ivey, Sean Brown, Anand S. Mehta, Richard R. Drake, Elizabeth S. Yeh, Marvella E. Ford, Peggi M. Angel. Potential differences in stromal patterns from breast cancer metastatic lymph between South Carolina sea islander black women and white women [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-07-02.