Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial....

Area of Science:

• Oncology
• Metabolic research
• Preventive medicine

Background:

• Cancer cells display metabolic flexibility, utilizing both glycolysis and oxidative phosphorylation.
• Metformin, an inhibitor of oxidative phosphorylation, combined with fasting, has shown preclinical promise in activating the PP2A-GSK3ß-Mcl1 axis and inhibiting tumor growth.
• Rising cancer drug costs necessitate exploration of low-cost, effective preventive interventions.

Purpose of the Study:

• To evaluate the effect of metformin and nightly fasting on breast cancer cell proliferation.
• To assess the safety and tolerability of this combined intervention.
• To explore a low-cost preventive strategy for hormone receptor-positive breast cancer and ductal carcinoma in situ (DCIS).

Main Methods:

• A window-of-opportunity trial involving participants with hormone receptor-positive invasive breast cancer or DCIS.
• Randomization to either nightly fasting (≥16 hours) with metformin and continuous glucose monitoring, or continuous glucose monitoring alone.
• Primary endpoint: change in Ki67 proliferation index; co-primary endpoint: difference in Ki67 in adjacent DCIS or high-risk lesions.

Main Results:

• The combination of metformin and nightly fasting was evaluated for safety as a primary interim endpoint.
• Most adverse events were low-grade and unrelated to treatment.
• No dose-limiting toxicities were observed, allowing for a shortened metformin escalation period.

Conclusions:

• Metformin and nightly fasting demonstrate a safe profile for breast cancer patients.
• This intervention has the potential to reduce cancer cell proliferation.
• The findings support further investigation in large-scale primary prevention studies for at-risk women.