Abstract 6286: Metabolic abnormalities are early predictors of liver metastasis in patients with ER+ breast tumors

Abstract Approximately 70% of human breast cancers express estrogen receptor alpha (ERα), providing a potential for targeted endocrine therapy for patients. Unfortunately, 30-40% of ER+ patients still experience recurrence and metastasis, with a 5-year relative overall survival rate of just 24% for patients with metastatic disease. In our preliminary analysis of the data from a large cohort of ER+ MBC patients, liver metastases were associated with reduced overall survival compared to other sites, while on the standard of care estrogen receptor antagonist, Fulvestrant (Fulv). This supports data from previous clinical trials showing that patients with liver metastases are less responsive to estrogen receptor alpha (ERα) targeting endocrine therapies compared to patients with bone or lung metastases. However, the factors underlying site-specific responses of MBC to ER antagonists are unknown. In this study, we investigated the concept that response of liver metastatic tumors is impacted by systemic glucose metabolism and the presence of liver metastatic tumors in turn will affect glucose homeostasis in the body. In our preliminary studies, metastatic liver tumors upregulated expression of enzymes that increased glycogen deposition in tumor cells in response to Fulv. Further analysis showed that a ketogenic diet restored Fulv response of metastatic liver tumors. Based on these results, we investigated if there was a relationship between metastatic site and response to endocrine therapy and if the metabolic status related to glucose homeostasis impacts metastatic disease response. We also searched if glucose homeostasis abnormalities can be indicators of liver metastasis. We obtained electronic health records from 192 patients with stage IV estrogen receptor positive breast cancer and analyzed glucose metabolism and liver panel markers including ALT, AST and ALP. Our results showed that more than 85% of patients with liver metastases have another accompanying metastasis and these patients are at a higher risk of diabetes diagnosis compared to other metastatic site patients. A higher % of patients with liver metastasis were deceased. We also observed increased levels of ALT, AST and ALP with liver metastasis and our preliminary analysis indicates that these blood biomarkers along with metabolic disease status (diabetes, hypertension, lipidemia) are good predictors of liver metastasis. Detecting early changes in markers of glucose metabolism may provide an easy diagnostic tool for early detection of liver metastases as well as assessment of treatment response. This may lead to accurate adjustment of treatment choices with improved outcome of patients with liver metastases from breast cancer. Citation Format: Ayca Nazli Mogol, Mahima Goel, Audrey Lam, Debapriya Dutta, Betsy Barnick, Maria Grosse Perdekamp, Zeynep Madak Erdogan. Metabolic abnormalities are early predictors of liver metastasis in patients with ER+ breast tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6286.