Fenretinide in Young Women at Genetic or Familial Risk of Breast Cancer: A Placebo-Controlled Biomarker Trial.

Autor:	Aristarco V; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Serrano D; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Maisonneuve P; Division of Epidemiology and Biostatistics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Guerrieri-Gonzaga A; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Lazzeroni M; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Feroce I; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Macis D; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Cavadini E; Molecular Pharmacology Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan. Italy., Albertazzi E; San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), IRCCS San Raffaele Scientific Institute, Milan, Italy., Jemos C; Division of Pharmacy, IEO, European Institute of Oncology IRCCS, Milan, Italy., Omodeo Salè E; Division of Pharmacy, IEO, European Institute of Oncology IRCCS, Milan, Italy., Cortesi L; Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy., Massarut S; Department of Medical Oncology, CRO-Centro di Riferimento Oncologico, Aviano (PN), Italy., Gulisano M; Medical Oncology, Ospedale S. Bortolo, Vicenza, Italy., Daidone MG; Scientific Directorate, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Johansson H; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy., Bonanni B; Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology IRCCS, Milan, Italy.
Jazyk:	angličtina
Zdroj:	Cancer prevention research (Philadelphia, Pa.) [Cancer Prev Res (Phila)] 2024 Jun 04; Vol. 17 (6), pp. 255-263.
DOI:	10.1158/1940-6207.CAPR-23-0422
Abstrakt:	Fenretinide, a retinoid with a low-toxicity profile that accumulates in the breast, has been shown to prevent second breast cancer in young women. Fenretinide exhibits apoptotic and antiinvasive properties and it improves insulin sensitivity in overweight premenopausal women with insulin resistance. This study aimed to further characterize its role in cancer prevention by measuring circulating biomarkers related to insulin sensitivity and breast cancer risk.Sixty-two women, ages 20 to 46 years, healthy or who had already undergone breast cancer surgery, with a known BRCA1/2 mutation or a likelihood of mutation ≥20% according to the BRCAPRO model, were randomly assigned to receive fenretinide (200 mg/day) or placebo for 5 years (trial registration: EudraCT No. 2009-010260-41). Fasting blood samples were drawn at baseline, 12 and 36 months, and the following biomarkers were analyzed: retinol, leptin, adiponectin, retinol-binding protein 4 (RBP-4), total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, glucose, insulin, insulin-like growth factor (IGF-1), IGF-binding protein 3, sex hormone binding globulin (SHBG), testosterone, and vascular endothelial growth factor (VEGF).After 12 months of treatment, we observed a favorable effect of fenretinide on glucose (decrease; P = 0.005), insulin (decrease; P = 0.03), homeostatic model assessment index (decrease; P = 0.004), HDL cholesterol (increase; P = 0.002), even though these effects were less prominent after 36 months. Retinol and retinol-binding protein 4 markedly decreased (P < 0.0001) throughout the study. None of the other measured biomarkers changed. Prevention Relevance: Fenretinide exhibits beneficial effects on the metabolic profile, supporting its clinical use in breast cancer prevention especially in premenopausal women with a positive family history and pathogenic variants in BRCA1/2 genes. This finding requires further investigations in larger trials to confirm its role in breast cancer prevention. (©2024 American Association for Cancer Research.)
Databáze:	MEDLINE
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