By the Scientific Team of the Valter Longo Foundation
Triple-negative breast cancer is one of the most aggressive forms of breast carcinoma and often presents an altered metabolism, characterized by high glucose consumption. This feature can influence the response to therapy: tumor cells use sugars to sustain their growth, and their metabolic activity may help make them less sensitive to chemotherapy.
A new perspective comes from a study conducted by Dr. Francesca Ligorio and coordinated by Dr. Claudio Vernieri of the Fondazione IRCCS Istituto Nazionale dei Tumori in Milan. The research, published in the prestigious scientific journal Cell Metabolism (2025), used the BREAKFAST clinical trial to explore the potential of the fasting-mimicking diet in combination with neoadjuvant chemotherapy, that is, chemotherapy administered before surgery. The results suggest that this nutritional strategy may help modify the metabolism of tumor cells, potentially making them more sensitive to the action of drugs.
The study involved 30 patients with triple-negative breast cancer, divided into two groups. Both followed cycles of the fasting-mimicking diet, a five-consecutive-day eating program that reproduces some of the metabolic effects of fasting, in combination with standard chemotherapy, for up to eight cycles. In one of the two groups, metformin, a drug commonly used to treat diabetes, was also added to assess any additional benefits.
Through advanced molecular analyses, the researchers observed that in the patients who achieved the best therapeutic outcomes there was a rapid reduction in glycolytic activity, the process by which cells use glucose to produce energy. This metabolic change may help make tumor cells more vulnerable to chemotherapy, opening new prospects for improving treatment efficacy.
The clinical results are promising: 56.6% of participants achieved a pathological complete response, meaning no residual invasive tumor at the time of surgery. This is an encouraging figure compared with results reported in previous studies with chemotherapy alone. However, because the study did not include a control group treated with chemotherapy only, further studies will be needed to confirm the specific contribution of the fasting-mimicking diet. The addition of metformin, on the other hand, did not show significant additional benefits.
Despite the limited number of participants, the study represents an important step forward in understanding the link between tumor metabolism, nutrition and response to treatment. To build on these findings, new studies have already been launched to evaluate the combination of the fasting-mimicking diet with the most modern cancer therapies, including immunotherapy, a treatment that helps the immune system recognize and fight tumor cells.
The research also provided encouraging results on the feasibility and tolerability of the protocol, which was followed under close medical supervision. A reduction in visceral fat was observed, accompanied by a temporary decrease in muscle mass, largely recovered in the following period.
Overall, these results open new prospects for integrating targeted nutritional strategies into cancer care pathways. Although further clinical confirmation is needed, the study suggests that intervening on the metabolism of tumor cells through the fasting-mimicking diet could, in the future, represent a valuable support to conventional therapies. It is essential to emphasize that, during cancer treatment, nutritional protocols of this kind must be followed exclusively under specialist medical supervision.
Source:
Ligorio F, Vingiani A, Torelli T, Sposetti C, Drufuca L, Iannelli F, Zanenga L, Depretto C, Folli S, Scaperrotta G, Capri G, Bianchi GV, Ferraris C, Martelli G, Maugeri I, Provenzano L, Nichetti F, Agnelli L, Lobefaro R, Fucà G, Fotia G, Mariani L, Morelli D, Ladisa V, De Santis MC, Lozza L, Trecate G, Belfiore A, Brich S, Bertolotti A, Lorenzini D, Ficchì A, Martinetti A, Sottotetti E, Arata A, Corsetto P, Sorrentino L, Rediti M, Salvadori G, Minucci S, Foiani M, Apolone G, Pagani M, Pruneri G, de Braud F, Vernieri C. Early downmodulation of tumor glycolysis predicts response to fasting-mimicking diet in triple-negative breast cancer patients. Cell Metab. 2025 Feb 4;37(2):330-344.e7. doi: 10.1016/j.cmet.2024.11.004. Epub 2024 Dec 17. PMID: 39694040.