Calorie Restriction With or Without Metformin in Triple Negative Breast Cancer

  • End date
    Dec 31, 2024
  • participants needed
  • sponsor
    Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Updated on 25 January 2021
breast cancer
direct bilirubin
bilateral oophorectomy
gilbert's syndrome
primary tumor
triple negative breast cancer
progesterone receptor
gene amplification


Glucose starvation and metformin have synergistic antitumor effects that are mediated through the concomitant inhibition of glycolysis and mitochondrial oxidative phosphorylation. The BREAKFAST trial will evaluate the antitumor activity of combining cyclic fasting-mimicking diet (FMD), which reproduces the in vitro effects of glucose starvation, plus/minus metformin with standard preperative anthracycline-taxane chemotherapy in patients with stage I-III TNBC


Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, and is associated with the lowest cure rates in the limited-stage disease setting, as well as with the lowest overall survival in the metastatic setting. Preclinical studies indicate that cycles of fasting or calorie-restricted, low-carbohydrate, low-protein diets, also known as fasting-mimicking diets (FMDs), have synergistic cytotoxic effects when combined with chemotherapy agents, such as doxorubicin or cisplatin, in several in vitro and in vivo tumor models, including murine TNBC models. More recently, intermittent fasting has demonstrated highly synergistic antitumor effects when combined with metformin; of note, these effects are mediated through the concomitant inhibition of glycolysis (via fasting-induced hypoglycemia) and metformin-induced inhibition of mitochondrial oxidative phosphorylation (OXPHOS). Finally, small reports published so far indicate that cyclic fasting and FMDs are well tolerated in cancer patients, and can be safety combined with standard antitumor treatments.

Based on these data, the BREAKFAST trial was designed to investigate the antitumor activity of cyclic FMD, alone or in combination with metformin, in patients with localized TNBC. In this study, 90 patients with stage I-III TNBC will be randomized in a 1:1 ratio to receive approximately 6 months of standard preoperative anthracycline plus taxane chemotherapy in combination with eight triweekly cycles of 5-day FMD (Arm A), or the same chemotherapy-FMD regimen plus daily metformin (Arm B). The primary objective of the study is to demonstrate that one or both experimental treatments increase the rate of pCR from 45% (historical data) to 65%

Condition Breast Cancer, Breast Cancer, Diet and Nutrition, Chronic Diarrhea, Skin Wounds, Chronic Shoulder Pain, Vaginal Atrophy, Adverse Effects, Drugs, Injection Port, Breast Cancer - HER2 Positive, Anal Dysplasia, Primary Immunodeficiency, Pediatric Health, Near-Sighted Corrective Surgery, Peripheral Arterial Occlusive Disease, Triple Negative Breast Cancer, Brain Function, Recurrent Respiratory Papillomatosis, Razor Bumps (Pseudofolliculitis Barbae), Metastatic Triple-Negative Breast Cancer
Treatment Metformin, Preoperative chemotherapy, Fasting-mimicking diet
Clinical Study IdentifierNCT04248998
SponsorFondazione IRCCS Istituto Nazionale dei Tumori, Milano
Last Modified on25 January 2021


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