Adipositas und Metabolisches Syndrom beim Mammakarzinom Priv. -Doz. Dr Adipositas und Metabolisches Syndrom beim Mammakarzinom Priv.-Doz. Dr. med. Stefan Krämer Leiter des Brustzentrums

Adipositas Body-Mass-Index WHO Definition

Assoziation zwischen Adipositas und Brustkrebs (Subtypen) Risikofaktor Postmenopause: ER + / PR + Prämenopause: ER – / PR – / HER2 – Ligibel JA et al. Am Soc Clin Oncol Educ Book 2013;3:52-59 Yang XR et al. J Natl Cancer Inst 2011;103:250-263

Cumulative incidence of first events (locoregional recurrences and distant metastases) in relation to body mass index (BMI) among 53,816 patients with early-stage breast cancer in Denmark, 1977 to 2006. Cumulative incidence of first events (locoregional recurrences and distant metastases) in relation to body mass index (BMI) among 53,816 patients with early-stage breast cancer in Denmark, 1977 to 2006. Marianne Ewertz et al. JCO 2011;29:25-31

Risk of death as a result of breast cancer and other causes in relation to body mass index (BMI) among 53,816 patients with early-stage breast cancer in Denmark, 1977 to 2006. Risk of death as a result of breast cancer and other causes in relation to body mass index (BMI) among 53,816 patients with early-stage breast cancer in Denmark, 1977 to 2006. Marianne Ewertz et al. JCO 2011;29:25-31

Adipositas und Prognose beim Mammakarzinom Overall survival HR = 1,33 95 % CI 1,21-1,47 Metaanalyse Protani et al. Breast Cancer Res Treat 2010;123:627-635

Metabolisches Syndrom Adipositas Diabetes – Insulinresistenz Hypercholesterinämie Hypertriglyceridämie Hypertonie Alberti et al. Circulation 2009;120:1640-1645

Metabolisches Syndrom Risikofaktor für Kardiovaskuläre Erkrankungen Prävalenz: 20 – 25 % Prävalenz ≥ 50 Jahre: 40 – 45 % Risikofaktor für Kardiovaskuläre Erkrankungen HR = 2-3 Alberti et al. Circulation 2009;120:1640-1645

Metabolisches Syndrom Risikofaktor für Brustkrebs (postmenopausal) HR = 1,52 Adipositas HR = 1,12 Diabetes HR = 1,19 Hypercholesterinämie HR = 1,39 Hypertriglyceridämie HR = 1,08 Hypertonie HR = 1,13 Esposito et al. Menopause 2013;20:1301-1309

Metabolisches Syndrom Cohortenstudie n = 287.320 Prognosefaktor bei Brustkrebs (postmenopausal) Mortalitätsrisiko (brustkrebsspezifisch) HR = 1,23 Bjørge et al. Cancer Epidemiol Biomarkers Prev 2010;19:1727-1745

Adipositas und metabolisches Syndrom unabhängige Risikofaktoren für die Brustkrebsinzidenz unabhängige Prognosefaktoren bei Brustkrebs (DFS und OS) … unabhängig vom Menopausenstatus

Pathophysiologische Interaktion zwischen Fettgewebe und Brustkrebs Insulinresistenz – chronische Inflammation – Adipokin Imbalance

Mechanismen der Adipositas-assoziierten Karzinogenese

AdipoCA-Studie am Brustzentrum der Uniklinik Köln Identifizierung neuer sezernierter Faktoren des peritumoralen Fettgewebes, die Wachstum und Metastasierung des Mammakarzioms propagieren Proben: peritumorales Fettgwebe versus distantes intramammäres Fettgewebe Untersuchung: - vergleichende Genexpressiosanalyse - Funktionelle Validierung neu identifizierter Kandidaten in vitro und in vivo Studienleitung: Priv.-Doz. Dr. med. Bettina Hanstein

Insulinresistenz IGF-1R Insulin → IGF-1 Signaltransduktion PI3k – Akt – mTOR RAS – RAF – MAPK Proliferation Anti-Apoptose

Therapeutische Intervention Breast Cancer Res Treat 2013 May;139(1):145-53. A phase I trial of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer BMC Cancer 2014 Mar 10;14:170. Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR). J Clin Oncol 2015 Oct 1;33(28):3169-76. Results of the Exercise and Nutrition to Enhance Recovery and Good Health for You (ENERGY) Trial: A Behavioral Weight Loss Intervention in Overweight or Obese Breast Cancer Survivors

Activation of IRS1 and Akt by mTOR inhibitors is prevented by the co-administration of anti-IGF-1R monoclonal antibodies (ganitumab) Activation of IRS1 and Akt by mTOR inhibitors is prevented by the co-administration of anti-IGF-1R monoclonal antibodies. Abbreviations: IGF1-R, insulin-like growth factor 1 receptor; IRS1, insulin receptor substrate 1; mTOR, mammalian target of rapamycin; PDK1, 3-phosphoinositide-dependent protein kinase 1; PI3K, phosphoinositide-3 kinase; PIP2, phosphatidylinositol bisphosphate; PIP3, phosphatidylinositol triphosphate; PTEN, phosphatase and tensin homologue deleted on chromosome ten; RAPTOR, regulatory associated protein of TOR; RICTOR, rapamycin-insensitive companion of mammalian target of rapamycin; TSC, tuberous sclerosis. according to Baselga J. The Oncologist 2011;16:12-19

Lifestyle-Intervention The German SUCCESS C Study - The First European Lifestyle Study on Breast Cancer.

Körperliche Aktivität und Ernährung Proportion of study participants achieving a weight loss of more than 5% and more than 10% of initial weight at 12 and 24 months. Proportion of study participants achieving a weight loss of more than 5% and more than 10% of initial weight at 12 and 24 months. Cheryl L. Rock et al. JCO 2015;33:3169-3176

Körperliche Aktivität / Sport und Lebensqualität Schmidt T, Weisser B, Jonat W, Baumann FT, Mundhenke C. Anticancer Res 2012;32(8):3229-33. Gentle strength training in rehabilitation of breast cancer patients compared to conventional therapy.

Adipositas / Metabolisches Syndrom – Brustkrebs nach D. Hauner und H. Hauner, TU München

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