超加工食品与黑人女性乳腺肿瘤组织中PI3K/AKT/MTOR信号通路蛋白表达之间的关联

Background: Ultra-processed food (UPF) consumption has been linked to increased breast cancer risk and poorer outcomes, potentially through metabolic/insulin resistance pathways. The PI3K/AKT/MTOR signaling pathways are frequently dysregulated in breast tumors. However, little is known about how UPF intake influences this pathway in breast tissue, particularly among Black women, who experience highest breast cancer mortality. Examining these associations may clarify diet-related molecular mechanisms underlying breast cancer disparities. Methods: We investigated tumor FFPE samples from 439 breast cancer cases who self-identified as Black/African American and participated in the well-established population-based study, the Women's Circle of Health Study. Tumor expressions for MTOR, phosphorylated (p)-MTOR, p-AKT, and p-P70S6K were analyzed by immunohistochemistry (IHC) and digitally scored (H-score 1%-300%). Foods and drinks consumed over 12 months before breast cancer diagnosis were assessed during home interviews by validated food-frequency questionnaires. UPFs were classified according to their degree of processing using the NOVA classification system. Multivariable logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations between UPF intake (per 1-SD increase) and protein expression (positive [H-score>0] vs. negative [H-score=0]), adjusting for age of breast cancer diagnosis, socioeconomic status, total energy intake, and body mass index at diagnosis. Results: Our participants consumed an average of 5.5 UPF servings/day before breast cancer diagnosis. More than 90% of tumors expressed MTOR and p-MTOR markers, whereas p-AKT and p-P70S6K were detected in 38% and 42% of cases, respectively. Higher UPF consumption was significantly associated with increased odds of nuclear p-AKT-positive tumors (OR = 1.23; 95% CI: 1.00-1.51) and cytoplasmic p-P70S6K-positive tumors (OR = 1.20; 95% CI: 1.00-1.47). Associations remained robust after restricting analyses to women with estrogen receptor (ER)-positive tumors or those without type 2 diabetes. However, heterogeneity by ER status was observed for MTOR expression: higher UPF intake was significantly associated with a threefold greater odds of cytoplasmic MTOR-positive tumors among ER-negative subtype (OR = 3.27; 95% CI: 1.19-16.46) but not among those with ER-positive cancer (OR = 0.91; 95% CI: 0.68-1.22; P-interaction=0.02). Conclusion: Our findings suggest that higher UPF intake was associated with activation of downstream PI3K/AKT/MTOR pathway in breast tumor tissue, highlighting a potential biological mechanism linking UPFs to breast cancer development. A deeper understanding of how UPF consumption influences tumor signaling may inform the development of tailored dietary recommendations and interventions for Black women.