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  • The influence of insulin-li...
    Engels, Charla C.; de Glas, Nienke A.; Sajet, Anita; Bastiaannet, Esther; Smit, Vincent T.H.B.M.; Kuppen, Peter J.K.; Seynaeve, Caroline; van de Velde, Cornelis J.H.; Liefers, Gerrit Jan

    Molecular oncology, April 2016, Letnik: 10, Številka: 4
    Journal Article

    Signaling via the Insulin-like Growth Factor type 1 Receptor (IGF1R) plays a crucial role in cancer development. In breast cancer (BC), IGF1R and estrogen receptor expression are correlated. In this current study we explored the hypothesis that postmenopausal hormone receptor positive (HR+ve) BC patients with high IGF1R tumor expression still have estrogen driven IGF1R stimulated tumor growth when treated with tamoxifen, resulting in detrimental clinical outcome compared to patients treated with exemestane. Additionally, we assessed the added value of metformin as this drug may lower IGF1R stimulation. Of 2,446 Dutch TEAM patients, randomized to either exemestane for 5 years or sequential treatment (tamoxifen for 2–3 years followed by exemestane for another 3–2 years) tumor tissue microarray sections were immunohistochemically stained for IGF1R. Overall Survival (OS), Breast Cancer specific Survival (BCSS) and Relapse-Free Survival (RFS) were assessed in patient subgroups with low and high IGF1R expression, and in patients with or without metformin use. High IGF1R tumor expression was significantly associated with exemestane therapy for RFS (Hazard Ratio (HR) 0.74, 95% Confidence Interval (CI) 0.58–0.95, p = 0.02). In addition, the combination of metformin with exemestane resulted in improved efficacy, yielding a 5-yrs RFS of 95% (HR 0.32, 95% CI 0.10–1.00, p = 0.02, compared to sequential treatment). No relation was observed in tumors with low IGF-1R expression. This study suggests IGF1R as a potential biomarker of improved clinical outcome in HR+ve BC patients treated with exemestane. Adding metformin to exemestane treatment may add to this effect. •Breast tumor tissue sections from Dutch TEAM patients were immunohistochemically stained for IGF1R status.•Part of this cohort was using metformin because of Diabetes type 2.•Breast cancer patients on exemestane harboring high IGF1R tumor expression had significantly less breast cancer relapse.•The addition of metformin to exemestane treatment resulted in improved efficacy.•Dual blockade of insulin- and estrogen-related growth pathway may improve outcome in selective breast cancer patients.