Ketogenic Diet and Breast Cancer: Recent Findings and Therapeutic Approaches

Abstract

Breast cancer (BC), a complex disease with several influencing factors, is significantly impacted by dietary habits. The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has gained attention as a potential therapeutic approach, but its effects on BC remain unclear. This review seeks to summarize the current knowledge on the principles of the KD, its metabolic influence on BC cells, and the findings of recent clinical trials, in order to elucidate the potential therapeutic role of the KD in BC management. For these purposes, a comprehensive literature review was conducted selecting preclinical and clinical studies that investigate the relationship between the KD and BC. The selection criteria prioritized studies exploring the KD's metabolic effects on BC cells and current clinical trials involving the KD in BC management. The reviewed studies provide a diverse range of findings, with some suggesting potential benefits of the KD in inhibiting tumor growth and improving treatment response. However, robust clinical trials providing clear evidence of the KD's efficacy as a standalone therapeutic approach in BC are still lacking. There are also significant concerns regarding the safety and long-term effects of sustained ketosis in cancer patients. The therapeutic potential of the KD in BC remains an area of active research and debate. While preliminary findings are promising, definitive conclusions are hindered by inconsistent results and limited human trial data. Future research, specifically well-structured, large-scale clinical trials, is necessary to provide a comprehensive understanding of the role of the KD in BC treatment. Until then, caution should be exercised in its application, and patients should continue prioritizing evidence-based, standard-of-care treatments.

Keywords: breast cancer; glycemic load; integrated treatments; ketogenesis; ketogenic diet; proteins.

Figure 1

Timeline of the evolution of the ketogenic diet.

Figure 2

Schematic representation of the most commonly used ketogenic diet regimens.

Figure 3

Molecular processes influenced by a ketogenic diet. (A) The low carbohydrate intake obtained through a ketogenic diet results in the decrement of glucose, insulin, and IGF-1. As a consequence, tumor-promoting pathways, like the PI3K/Akt pathway, are inhibited, as iss the production of ATP in dysfunctional mitochondria. (B) Ketone bodies can be metabolized by cancer cells only in presence of O₂. In the hypoxic condition typical of tumor cells, BHB cannot be metabolized due to the absence of SCOT, BDH1, and ACAT1. (C) BHB favors the gene transcription mediated by Nrf2, with the consequent production of glutathione able to detoxify cells from ROS. In addition, BHB inhibits the effects of several members of the HDAC family, thus inhibiting the proliferation and survival of cancer cells. In parallel, BHB-mediated HDAC-inhibition is responsible for the increase in the cytotoxic effects of chemotherapy on cancer cells.