Abstract A071: Deciphering the normal breast microenvironment in Black women and White women

Abstract Despite having similar incidence of breast cancer, black women (BW) are typically diagnosed with more aggressive subtypes of breast cancer compared to white women (WW). One mediator contributing to the disparity in breast cancer mortality rates is the distinct tumor microenvironments (TME) associated with BW and WW. Yet, characterization of the normal microenvironment (NME) in breast tissue and how they may associate with breast cancer risk factors remains unknown. Contemporary literature reports that TMEs from BW and WW with breast cancer are characterized with higher densities of pro-tumorigenic macrophages (M2) and cancer-associated adipocytes have been observed in BW compared to WW, and typically associated with worse breast cancer prognosis. While the TME has been shown to be critical for breast cancer progression, the lack of characterization of the NME is a limiting factor towards understanding the molecular differences between a normal and cancerous breast microenvironment. We hypothesize that characterizing the tissue compositions in the breast NME could elucidate unique molecular signatures that may be contributing to distinct alterations that are driving the disparity in breast cancer aggressiveness in BW. The cohorts consisted of normal breast tissue from BW (n=20) and WW (n=20) with breast cancer risk determined by Gail score. The Gail model is a well-established tool used to assess the 5-year risk of developing invasive breast cancer based on demographic and clinical data. All tissues were obtained from the Susan G. Komen tissue bank and used with institutional permission. Profiles of N-glycans, a glucose metabolism-linked post-translational modification, were characterized in normal breast tissue from BW and WW at risk for breast cancer using matrix assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI). Tissue from both cohorts were characterized based on their tissue compositions including areas rich in stroma, adipocytes, and crown like structures (CLSs), a pro-inflammatory process consisting of dying adipocytes surrounded by stroma and macrophages. Nearly 70 N-glycans were identified in the NME from both BW and WW. When comparing N-glycan peaks between premenopausal and postmenopausal women, one N-glycan peak (m/z 1905.633) was significantly higher in the premenopausal group (p<0.0001) regardless of genetic ancestry. However, when comparing peak m/z 1905.633 based on genetic ancestry, premenopausal and postmenopausal BW had significantly higher peak intensities compared to premenopausal and postmenopausal WW (premenopausal BW vs WW, p = 0.024; postmenopausal BW vs WW, p = 0.028). Overall, the data suggests that there may be distinct N-glycan structures associated with premenopausal and postmenopausal women based on genetic ancestry. Characterizing the NME from BW and WW at risk for breast cancer may help towards understanding potential breast stroma priming molecular signatures contributing to differences in breast cancer aggressiveness observed in BW compared to WW. Citation Format: Denys Rujchanarong, Anand Mehta, Richard R. Drake, Marvella E. Ford, Peggi M. Angel. Deciphering the normal breast microenvironment in Black women and White women [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A071.