Interplay Between Estrogen Signaling and Metabolic Biomarkers in Breast Cancer Progression

Background: Breast cancer growth involves androgen and estrogen signaling and metabolism. Adipokines and insulin resistance modulate hormone sensitivity, invasion and growt. Aims of the study: This study aims to investigate the association between estrogen receptor pathway and metabolic factors in female patients with breast cancer, and their impact on the tumor characteristics and clinical outcomes. And to investigate the role of insulin resistance and adipokine (leptin and adiponectin) imbalance as a predictor of tumor. Methodology: A case–control study was conducted from April 2025 to February 2026 at an oncology center in Iraq, including 80 breast cancer patients and 30 matched healthy controls. Diagnosis was confirmed histopathologically, and staging followed the TNM system. ER status was assessed by immunohistochemistry (≥10% positivity). Blood samples were collected, centrifuged, and serum stored at −20°C. Glucose was measured enzymatically, while insulin, leptin, and adiponectin were analyzed using ELISA. HOMA-IR was calculated. Only newly diagnosed patients were included; those with metabolic or endocrine disorders were excluded. Result: Most patients were ≥50 years (57.5%) with grade II disease (45.0%) and 55.0% had early stage disease. 65.0% showed ER positivity. Biomarkers showed significant differences between patients and controls (p < 0.001) revealing insulin resistance and altered adipokines. Metabolic biomarkers were worse among ER-negative patients. ER level was negatively associated with tumor grade and stage, and biomarkers. Multivariate analysis revealed ER-negative status, HOMA-IR and leptin as indicators of disease progression, with adiponectin showing borderline significance. Conclusions: Loss of the estrogen receptor (ER) and metabolic dysfunction are key factors in the progression of breast cancer. Insulin resistance and overproduction of leptin stimulate tumor growth through the PI3K/Akt pathway, and decreased adiponectin levels diminish anti-proliferative activity increasing tumor inviveness.