Liver Metastatic Breast Cancer: Epidemiology, Dietary Interventions, and Related Metabolism

Abstract

The median overall survival of patients with metastatic breast cancer is only 2-3 years, and for patients with untreated liver metastasis, it is as short as 4-8 months. Improving the survival of women with breast cancer requires more effective anti-cancer strategies, especially for metastatic disease. Nutrients can influence tumor microenvironments, and cancer metabolism can be manipulated via a dietary modification to enhance anti-cancer strategies. Yet, there are no standard evidence-based recommendations for diet therapies before or during cancer treatment, and few studies provide definitive data that certain diets can mediate tumor progression or therapeutic effectiveness in human cancer. This review focuses on metastatic breast cancer, in particular liver metastatic forms, and recent studies on the impact of diets on disease progression and treatment.

Keywords: breast cancer liver metastasis; fasting-mimicking diet; western diet.

Figure 1

Suggested liver metastatic cancer metabolism in normal diet or fasting-mimicking diet. In the presence of glucose, the breast cancer cells metastasized to the liver mainly go through glycolysis to produce pyruvate, which is converted to acetyl-CoA via oxidative decarboxylation. Acetyl-CoA enters the tricarboxylic acid cycle (TCA cycle) and generates adenosine-3-phosphate (ATP) for cell survival and proliferation. Excessive glucose can be stored as glycogen for further usage. When glucose is limited (under a fasting-mimicking diet), the cancer cells switch to acquire ATP by fatty acid oxidation. The fatty acid oxidation is also highly activated in peripheral hepatocytes, where abundant acetyl-CoA feeds into ketogenesis and produces a large amount of acetoacetate and β-hydroxybutyrate. The liver does not use ketone bodies for energy because it lacks the necessary enzyme thiophorase (beta ketoacyl-CoA transferase). The unclear part is how these released ketone bodies function on breast cancer cells.