Core Viewpoint - The article discusses the potential of fasting to enhance the efficacy of endocrine therapy in HR+ breast cancer patients, highlighting a recent study that identifies glucocorticoid activation as a key mechanism behind this effect [2][4][11]. Group 1: Fasting and Endocrine Therapy - HR+ breast cancer, which includes estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+) types, accounts for 75% of all breast cancer diagnoses, with endocrine therapy being the primary treatment method [2][6]. - Standard endocrine therapy often faces limitations due to primary or acquired resistance, leading to tumor recurrence and progression after several years of treatment [6][7]. - Periodic fasting has been shown to enhance the effects of standard endocrine therapy and delay the onset of acquired resistance, although the underlying mechanisms were previously unclear [7][9]. Group 2: Recent Research Findings - A study published in Nature by researchers from the Netherlands Cancer Institute and the University of Genoa on December 10, 2025, demonstrates that fasting enhances breast cancer treatment efficacy through glucocorticoid activation [3][4]. - The research indicates that fasting induces extensive epigenetic reprogramming in ER+ breast cancer models, activating glucocorticoid receptors (GR) and progesterone receptors (PR), while reducing the activity of AP-1 family members [7][9]. - In human patients undergoing periodic simulated fasting diets, increased levels of progesterone and cortisol were observed, correlating with the activation of GR and negative correlation with proliferation markers in tumor samples [9][11]. Group 3: Implications for Treatment - The study suggests that the activation of glucocorticoid receptors plays a critical role in enhancing the activity of endocrine therapy during fasting, indicating the potential for evaluating corticosteroids as adjuncts to endocrine treatment [11].