Abstract P3-14-13: Metabolic links to socioeconomic stresses uniquely affecting race in normal breast tissue at risk for breast cancer

Abstract A primary difference between black women (BW) and white women (WW) diagnosed with breast cancer is not incidence, but aggressiveness of the tumor. Black women have higher mortalities with similar incidence of breast cancer compared to other race/ethnicities, and are diagnosed at a younger age with more advanced tumors with double the rate of lethal, triple negative breast cancers. There is ongoing debate regarding whether the underlying cause of higher mortality is related to healthcare inequalities or due to ancestry dependent molecular features found in normal breast tissue that facilitate the aggressive phenotype found in black women. One hypothesis is that chronic social and economic stressors result in molecular responses that create a tumor permissive tissue microenvironment in normal breast tissue, and these chronic stresses differ by race/ethnicity. In this study, we investigate molecular pattern changes in tissue N-glycosylation in a cohort of ancestry defined normal breast tissue from BW and WW with significant 5-year risk of breast cancer by Gail score. N-glycosylation, a glucose metabolism-linked post-translational modification attached to an asparagine (N) residue, was tested against social stressors. Social stresses included marital status, single, education, economic status (income), personal reproductive history, the risk factors BMI and age. Normal breast tissue microarrays from the Susan G. Komen tissue bank (WB=43; WW= 43) were used to evaluate glycosylation against socioeconomic stress and risk factors. There was no significant difference in age (Median age BW 42.5, 95% CI [40.0, 45.0]; WW 42.0, 95% CI [39.7, 44.3]). A subgroup of women had similar BMI (BW, n=24 Median BMI 29.5, 95% CI [27.6, 32.3]; WW, n=24 28.3, 95% CI [23.5, 31.6]. BW women had an overall lower median risk by 5-year Gail score, which, (BW 9.4, 95% CI [8.9, 9.9]; WW 10.4, 95% CI [8.1, 12.6]). Area under the receiver operating curve (AUC) ≥0.70, Brown/Wilson p-value <0.001 was used to assess for individual glycosylation differences in normal breast tissue at risk for breast cancer. Out of 55 N-glycans profiled in normal breast by glycomics mass spectrometry, one N-glycan appeared dependent on ancestry with high sensitivity and specificity (AUC 0.788, Brown/Wilson p-value<0.0001). For women of the same BMI, a total of 12 N-glycans could report potential ancestry-dependent differences. Interestingly, when we fit a linear regression model with ancestry as group variable and socioeconomic covariates as predictors, different N-glycans associated with different socioeconomic stresses. Five N-glycans in particular linked to different socioeconomic stresses for both BW and WW. For white women, household income was strongly associated to certain N-glycans, while for black women, marriage status (married and single) was strongly associated with the same N-glycan signature. Current work focuses on understanding if combined N-glycan biosignatures can further help understand normal breast tissue at risk. The data suggests that metabolic patterns linked to socioeconomic stresses may contribute to breast cancer risk dependent on ancestry. This study lays the foundation for understanding the complexities linking socioeconomic stresses and molecular factors to their role in ancestry dependent breast cancer risk and aggressiveness in black women. Citation Format: Peggi M Angel, Yeonhee Park, Danielle A Scott, Denys Rujchanarong, Sean Brown, Richard R Drake, George E Sandusky, Harikrishna Nakshatri. Metabolic links to socioeconomic stresses uniquely affecting race in normal breast tissue at risk for breast cancer [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 P3-14-13.