Financiado en parte por Janssen Research and Development
Time-Restricted Eating and Metformin in Invasive Breast Cancer or DCIS: A Randomized, Phase IIb, Presurgical Trial. Preliminary Safety Analysis
Briata IM, Spinaci S, Thomas PS, Serrano D, Buttiron Webber T, Gandolfo N, Guasone F, Rattaro A, Firpo E, D'amico M, Rutigliani M, Oliva M, Gualco M, Peresi M, Uncini S, Guerrieri-Gonzaga A, Johansson H, Gandini S, Lazzeroni M, Accornero CA, Pala O, Minucci S, Intra M, Veronesi P, Vornik LA, Garcia-Gonzalez A, Lozano MC, Heckman-Stoddard BM, Dimond E, Sauter ER, Vilar E, Bonanni B, DeCensi A
Cancer prevention research (Philadelphia, Pa.) · 0 citas
Etiquetas de revisión
Vínculos de autores con la industriaFinanciado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Ensayo controlado aleatorizado (indexado por PubMed)
- Estudiado en
- Personas
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Universidad u hospital
- Istituto Europeo di Oncologia
- Gobierno
- Ministero della Salute
- Organización sin fines de lucro
- Rising Tide Foundation
- Universidad u hospital
- University of Texas MD Anderson Cancer Center
- Gobierno
- National Cancer Institute
- Empresa
- Janssen Research and Development
- Gobierno
- NCI NIH HHS
- Gobierno
- National Cancer Institute (NCI)
- Gobierno
- Ministero della Salute (Italy Ministry of Health)
- Universidad u hospital
- Istituto Europeo di Oncologia (IEO)
- Autores
- Al menos un autor declara un vínculo económico con la industria
- Subvenciones
- Ministero della Salute (RF-2019); Ministero della Salute (RF-2019-12370733); National Cancer Institute (UG1CA242609)
Según 10 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2025-10-29 · Cancer Prev Res (Phila) · vol. 19 · número 1 · págs. 25–32
- Editorial
- American Association for Cancer Research
- Citado
- 0 citas · más que el 19% de estudios similares · 0.0× el promedio de su campo
- Referencias
- 28 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY-NC-ND
- Áreas de investigación
- Metabolism, Diabetes, and Cancer · Dietary Effects on Health · Cancer, Hypoxia, and Metabolism
- Palabras clave
- time-restricted eating, metformin, invasive breast cancer, ductal carcinoma in situ, Ki-67, oxidative phosphorylation, cancer metabolism, dose-limiting toxicity, drug repurposing, breast cancer prevention, continuous glucose monitoring, obesity-related cancer
- MeSH
- humans, carcinoma, ductal, breast, carcinoma, intraductal, noninfiltrating, breast neoplasms, metformin, blood glucose, hypoglycemic agents, preoperative care, fasting, follow-up studies, adult, aged, middle aged, female
33 autores
- Irene Maria Briata🇮🇹Ente Ospedaliero Ospedali Galliera
- Stefano Spinaci🇮🇹Ospedale Villa Scassi
- Parijatham S. Thomas🇺🇸The University of Texas MD Anderson Cancer Center
- Davide Serrano🇮🇹European Institute of Oncology
- Tania Buttiron Webber🇮🇹Ente Ospedaliero Ospedali Galliera
- Nicoletta G. Gandolfo🇮🇹Ospedale Villa Scassi
- Flavio Guasone🇮🇹Ospedale Villa Scassi
- Andrea Rattaro🇮🇹Ospedale Villa Scassi
- Emma Firpo🇮🇹Ospedale Villa Scassi
- Mauro D’Amico🇮🇹Ente Ospedaliero Ospedali Galliera
- Mariangela Rutigliani🇮🇹Ente Ospedaliero Ospedali Galliera
- Martino Oliva🇮🇹Ente Ospedaliero Ospedali Galliera
- Marina Gualco🇮🇹Ospedale Villa Scassi
- Monica Peresi🇮🇹Ospedale Villa Scassi
- Stefania Uncini🇮🇹Ospedale Villa Scassi
- Aliana Guerrieri‐Gonzaga🇮🇹European Institute of Oncology
- Harriet Ann Johansson🇮🇹European Institute of Oncology
- Sara Gandini🇮🇹European Institute of Oncology
- Matteo Lazzeroni🇮🇹European Institute of Oncology
- Chiara Arianna Accornero🇮🇹European Institute of Oncology
- Oriana Pala🇮🇹European Institute of Oncology
- Saverio Minucci🇮🇹European Institute of Oncology
- Mattia Intra🇮🇹European Institute of Oncology
- Paolo Veronesi🇮🇹European Institute of Oncology
- Lana A. Vornik🇺🇸The University of Texas MD Anderson Cancer Center
- Araceli García-González🇺🇸The University of Texas MD Anderson Cancer Center
- M.C. García Lozano🇺🇸The University of Texas MD Anderson Cancer Center
- Brandy M. Heckman‐Stoddard🇺🇸National Institutes of Health; National Cancer Institute
- Eileen P. Dimond🇺🇸National Institutes of Health; National Cancer Institute
- Edward R. Sauter🇺🇸National Institutes of Health; National Cancer Institute
- Eduardo Vilar🇺🇸The University of Texas MD Anderson Cancer Center
- Bernardo Bonanni🇮🇹European Institute of Oncology
- Andrea DeCensi🇵🇹🇮🇹 · autor de correspondenciaChampalimaud Foundation; Ente Ospedaliero Ospedali Galliera
Resumen
El texto original del estudio, en el idioma en que se publicó.
Cancer cells exhibit metabolic flexibility between anaerobic glycolysis and oxidative phosphorylation. Preclinical data showed that metformin, an oxidative phosphorylation inhibitor, combined with fasting-induced hypoglycemia led to activation of the PP2A-GSK3ß-Mcl1 axis and inhibition of tumor growth. A window-of-opportunity trial was designed to evaluate the effect of metformin and nightly fasting on proliferation in invasive breast cancer or ductal carcinoma in situ (DCIS). The primary endpoint is the pretreatment/posttreatment change of Ki67 in cancer tissue, and the co-primary endpoint is the difference in posttreatment Ki67 in cancer-adjacent DCIS or high-risk lesions. Participants with hormone receptor-positive invasive breast cancer or DCIS candidates to surgery are being accrued and randomized to either (i) fasting for ≥16 hours nightly, plus nutritional counseling and daily metformin with continuous glucose monitoring, or (ii) continuous glucose monitoring. The intervention lasts 4 to 6 weeks with gradual metformin ramp up to limit gastrointestinal disturbances. The safety of the combination was evaluated as a primary interim endpoint. The frequency of dose-limiting toxicity (≥G3 adverse events related to treatment) was assessed in the first 14 participants in the experimental arm. Most adverse events were of low grade (G1: 50; 90.9%) and unrelated to the treatment (G1: 26 unrelated; 52%). No one discontinued treatment because of toxicity, and no dose-limiting toxicities were observed, so the escalation phase of metformin was significantly shortened from 7 to 3 days. The results of this project will expand knowledge of this prevention approach and possibly provide the basis for large-scale primary prevention studies in at-risk women.
Prevention relevance
In a context of rising cancer drug costs, this research explores a low-cost treatment to optimize breast cancer preventive intervention. The approach is safe and based on repurposed drugs that could enhance prevention strategies for obesity- and insulin-related cancers, offering immediate applicability to a large-scale trial in women at risk.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY-NC-ND).
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