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Cancer Prev Res (Phila) ; 17(6): 255-263, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38530139

RESUMO

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.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Fenretinida , Humanos , Fenretinida/uso terapêutico , Fenretinida/administração & dosagem , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Proteína BRCA2/genética , Proteína BRCA1/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Predisposição Genética para Doença , Mutação , Resistência à Insulina , Método Duplo-Cego
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