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CC BY-NC-ND 4.0 · Adipositas - Ursachen, Folgeerkrankungen, Therapie 2021; 15(02): 62-70
DOI: 10.1055/a-1387-9357
Review

Adipositas in der gynäkologischen Onkologie

Obesity in Gynecologic Oncology
Heinz Kölbl
1   Klinische Abteilung für Allgemeine Gynäkologie und Gynäkologische Onkologie, Universitätsklinik für Frauenheilkunde, Medizinische Universität Wien, Wien, Österreich
,
Thomas Bartl
1   Klinische Abteilung für Allgemeine Gynäkologie und Gynäkologische Onkologie, Universitätsklinik für Frauenheilkunde, Medizinische Universität Wien, Wien, Österreich
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ZUSAMMENFASSUNG

Als Folge der weltweit seit Jahrzehnten ansteigenden Adipositasprävalenz stellen die zunehmende Anzahl an Neudiagnosen adipositasassoziierter Malignome und damit einhergehende diagnostische und therapeutische Implikationen gynäkoonkologische Behandlungsstrategien vor eine Herausforderung. Im Spiegel der aktuellen Studienlage besteht solide Evidenz für eine unabhängige, linear positive Korrelation zwischen einem pathologisch erhöhten Body-Mass-Index und der Erkrankungswahrscheinlichkeit für Endometrium- und postmenopausale Mammakarzinome. Die Pathogenese ist komplex und Gegenstand intensiver Forschung, pathologisch erhöhte Serumspiegel von Sexualsteroiden und Adiponektinen, eine adipositasinduzierte Insulinresistenz sowie systemische Inflammationsprozesse werden als ursächlich diskutiert. Für andere gynäkologische Malignome zeigt sich die wissenschaftliche Evidenz weniger solide, Adipositas erscheint als Risikofaktor für epitheliale Ovarial,-Zervix und Vulvakarzinome von vergleichsweise untergeordneter klinischer Relevanz. Ein negativer Einfluss auf die Prognose und das onkologische Outcome zeigt sich hingegen für alle Tumorentitäten nachvollziehbar, wobei eine abschließende Bewertung, ob dieser Effekt korrelativ oder kausal zu interpretieren ist, weiterhin aussteht.

ABSTRACT

The decades-long global obesity epidemic has resulted in steady increase in the incidence of obesity-related malignancies. The associated diagnostic and therapeutic implications present a clinical challenge for gynecologic oncology treatment strategies. Recent studies have provided solid evidence for an independent, linear, positive correlation between a pathologically increased body mass index and the probability of developing endometrial or postmenopausal breast cancer. The pathogenesis is complex and the subject of current research. Proposed causes include pathologically increased serum levels of sexual steroids and adiponectin, obesity-induced insulin resistance, and systemic inflammatory processes. The scientific evidence for an association between obesity and other gynecological malignancies is, however, less solid. The clinical relevance of obesity as a risk factor for epithelial ovarian cancer, cervical cancer and vulvar cancer appears to be negligible. Nevertheless, obesity appears to have a negative impact on prognosis and oncologic outcomes for all gynecological cancers. Whether or not this effect can be interpreted as correlative or causal is still a subject of ongoing debate.

Schlüsselwörter

Adipositas - gynäkologische Malignome - BMI

Key words

obesity - gynecological malignancies - BMI


Publication History

Article published online:
29 June 2021

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • Literatur

  • 1 Hales CM, Fryar CD, Carroll MD. et al. Trends in obesity and severe obesity prevalence in US youth and adults by sex and age, 2007-2008 to 2015-2016. JAMA 2018; 319: 1723-1725
    CrossrefPubMedSearch in Google Scholar
  • 2 Berghöfer A, Pischon T, Reinhold T. et al. Obesity prevalence from a European perspective: A systematic review. BMC Public Health 2008; 8: 200
    CrossrefPubMedSearch in Google Scholar
  • 3 Prammer-Waldhör M. Jahrbuch der Gesundheitsstatistik, Wien: Statistik Austria 2019. Online (Stand: 29.09.2020): https://www.statistik.at/web_de/services/publikationen/4/index.html?includePage=detailedView&sectionName=Gesundheit&pubId=543
    PubMed
  • 4 Vucenik I, Stains JP. Obesity and cancer risk: Evidence, mechanisms, and recommendations. Ann N Y Acad Sci 2012; 1271: 37-43.
    CrossrefPubMedSearch in Google Scholar
  • 5 Laviano A, Koverech A, Mari A. Cachexia: Clinical features when inflammation drives malnutrition. Proc Nutr Soc 2015; 74: 348-354
    CrossrefPubMedSearch in Google Scholar
  • 6 Holzer RG, Park EJ, Li N. et al. Saturated fatty acids induce c-Src clustering within membrane subdomains, leading to JNK activation. Cell 2011; 147: 173-184
    CrossrefPubMedSearch in Google Scholar
  • 7 Feuerer M, Herrero L, Cipolletta D. et al. Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 2009; 15: 930-939
    CrossrefPubMedSearch in Google Scholar
  • 8 McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity 2014; 41: 36-48
    CrossrefPubMedSearch in Google Scholar
  • 9 Weisberg SP, McCann D, Desai M. et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808
    CrossrefPubMedSearch in Google Scholar
  • 10 Font-Burgada J, Sun B, Karin M. Obesity and Cancer: The Oil that Feeds the Flame. Cell Metab 2016; 23: 48-62
    CrossrefPubMedSearch in Google Scholar
  • 11 Solinas G, Vilcu C, Neels JG. , et al. JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 2007; 6: 386-397
    CrossrefPubMedSearch in Google Scholar
  • 12 Aguirre V, Werner ED, Giraud J. et al. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem 2002; 277: 1531-1537
    CrossrefPubMedSearch in Google Scholar
  • 13 Nielsen S, Guo Z, Johnson CM. et al. Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113: 1582-1588
    CrossrefPubMedSearch in Google Scholar
  • 14 Yang Y, Ju D, Zhang M. et al. Interleukin-6 stimulates lipolysis in porcine adipocytes. Endocrine 2008; 33: 261-269
    CrossrefPubMedSearch in Google Scholar
  • 15 McCampbell AS, Broaddus RR, Loose DS. et al. Overexpression of the insulin-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium. Clin Cancer Res 2006; 12: 6373-6378
    CrossrefPubMedSearch in Google Scholar
  • 16 Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: A review of current evidence. Endocr Rev 2012; 33: 547-594
    CrossrefPubMedSearch in Google Scholar
  • 17 Antuna-Puente B, Feve B, Fellahi S. et al. Adipokines: The missing link between insulin resistance and obesity. Diabetes Metab 2008; 34: 2-11
    CrossrefPubMedSearch in Google Scholar
  • 18 Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci 2015; 36: 461-470
    CrossrefPubMedSearch in Google Scholar
  • 19 Yager JD. Mechanisms of estrogen carcinogenesis: The role of E2/E1-quinone metabolites suggests new approaches to preventive intervention-A review. Steroids 2015; 99: 56-60
    CrossrefPubMedSearch in Google Scholar
  • 20 Cooper LA, Page ST, Amory JK. et al. The association of obesity with sex hormone-binding globulin is stronger than the association with ageing-implications for the interpretation of total testosterone measurements. Clin Endocrinol (Oxf) 2015; 83: 828-833
    CrossrefPubMedSearch in Google Scholar
  • 21 Lukanova A, Lundin E, Micheli A. et al. Circulating levels of sex steroid hormones and risk of endometrial cancer in postmenopausal women. Int J Cancer 2004; 108: 425-432
    CrossrefPubMedSearch in Google Scholar
  • 22 He XY, Liao YD, Yu S. et al. Sex hormone binding globulin and risk of breast cancer in postmenopausal women: a meta-analysis of prospective studies. Horm Metab Res 2015; 47: 485-490
    Thieme ConnectPubMedSearch in Google Scholar
  • 23 McCullough ML, Patel AV, Patel R. , et al. Body mass and endometrial cancer risk by hormone replacement therapy and cancer subtype. Cancer Epidemiol Biomarkers Prev 2008; 17: 73-79
    CrossrefPubMedSearch in Google Scholar
  • 24 Onstad MA, Schmandt RE, Lu KH. Addressing the role of obesity in endometrial cancer risk, prevention, and treatment. J Clin Oncol 2016; 34: 4225-4230
    CrossrefPubMedSearch in Google Scholar
  • 25 Wise MR, Jordan V, Lagas A. et al. Obesity and endometrial hyperplasia and cancer in premenopausal women: A systematic review. Am J Obstet Gynecol 2016; 214: 689.e1-689.e17
    CrossrefPubMedSearch in Google Scholar
  • 26 Calle EE, Rodriguez C, Walker-Thurmond K. et al. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. Adults N Engl JMed 2003; 348: 1625-1638
    CrossrefPubMedSearch in Google Scholar
  • 27 Emaus MJ, Van Gils CH, Bakker MF. et al. Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study. Int J Cancer 2014; 135: 2887-2899
    CrossrefPubMedSearch in Google Scholar
  • 28 Suzuki R, Orsini N, Saji S. et al. Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status-a meta-analysis. Int J Cancer 2009; 124: 698-712
    CrossrefPubMedSearch in Google Scholar
  • 29 Neuhouser ML, Aragaki AK, Prentice RL. et al. Overweight, obesity, and postmenopausal invasive breast cancer risk: a secondary analysis of the womenʼs health initiative randomized clinical trials. JAMA Oncol 2015; 1: 611-621
    CrossrefPubMedSearch in Google Scholar
  • 30 Pierobon M, Frankenfeld CL. Obesity as a risk factor for triple-negative breast cancers: A systematic review and meta-analysis. Breast Cancer Res Treat 2013; 137: 307-314
    CrossrefPubMedSearch in Google Scholar
  • 31 Schoemaker MJ, Nichols HB, Wright LB. et al. Association of body mass index and age with subsequent breast cancer risk in premenopausal women. JAMA Oncol 2018; 4: e181771
    CrossrefPubMedSearch in Google Scholar
  • 32 Jiralerspong S, Goodwin PJ. Obesity and breast cancer prognosis: evidence, challenges, and opportunities. J Clin Oncol 2016; 34: 4203-4216
    CrossrefPubMedSearch in Google Scholar
  • 33 Catherine MO, Christina MN, David CW. et al. Obesity and risk of ovarian cancer subtypes: Evidence from the ovarian cancer association consortium. Endocr Relat Cancer 2013; 20: 251-262
    CrossrefPubMedSearch in Google Scholar
  • 34 Hew KE, Bakhru A, Harrison E. et al. The effect of obesity on the time to recurrence in ovarian cancer: a retrospective study. Clin Ovarian Other Gynecologic Cancer 2013; 6: 31-35
    CrossrefPubMedSearch in Google Scholar
  • 35 Klapdor R, Hillemanns P, Woelber LL. et al. The influence of obesity on tumor recurrence in vulvar cancer patients. J Clin Oncol 2019; 37: e17130
    CrossrefPubMedSearch in Google Scholar
  • 36 Klapdor R, Hillemanns P, Wölber L. et al. Association between obesity and vulvar cancer recurrence: An analysis of the AGO-CaRE-1 study. Int J Gynecol Cancer 2020; 30: 920-926
    CrossrefPubMedSearch in Google Scholar
  • 37 Poorolajal J, Jenabi E. The association between BMI and cervical cancer risk: A meta-analysis. Eur J Cancer Prev 2016; 25: 232-238
    CrossrefPubMedSearch in Google Scholar
  • 38 Maruthur NM, Bolen SD, Brancati FL. et al. The association of obesity and cervical cancer screening: A systematic review and meta-analysis. Obesity (Silver Spring) 2009; 17: 375-381
    CrossrefPubMedSearch in Google Scholar
  • 39 Lacey jr. JV, Swanson CA, Brinton LA. et al. Obesity as a potential risk factor for adenocarcinomas and squamous cell carcinomas of the uterine cervix. Cancer 2003; 98: 814-821
    CrossrefPubMedSearch in Google Scholar
  • 40 Modesitt SC, Van Nagell jr.. The impact of obesity on the incidence and treatment of gynecologic cancers: a review. Obstet Gynecol Surv 2005; 60: 683-692
    CrossrefPubMedSearch in Google Scholar
  • 41 Clarke MA, Fetterman B, Cheung LC. et al. Epidemiologic evidence that excess body weight increases risk of cervical cancer by decreased detection of precancer. J Clin Oncol 2018; 36: 1184-1191
    CrossrefPubMedSearch in Google Scholar
  • 42 Ri M, Aikou S, Seto Y. Obesity as a surgical risk factor. Ann Gastroenterol Surg 2017; 2: 13-21
    CrossrefPubMedSearch in Google Scholar
  • 43 Bouwman F, Smits A, Lopes A. et al. The impact of BMI on surgical complications and outcomes in endometrial cancer surgery-an institutional study and systematic review of the literature. Gynecol Oncol 2015; 139: 369-376
    CrossrefPubMedSearch in Google Scholar
  • 44 Smits A, Lopes A, Das N. et al. Surgical morbidity and clinical outcomes in ovarian cancer – The role of obesity. BJOG 2016; 123: 300-308
    CrossrefPubMedSearch in Google Scholar
  • 45 Frumovitz M, Sun CC, Jhingran A. et al. Radical hysterectomy in obese and morbidly obese women with cervical cancer. Obstet Gynecol 2008; 112: 899-905
    CrossrefPubMedSearch in Google Scholar
  • 46 Lee K, Kruper L, Dieli-Conwright CM. et al. The impact of obesity on breast cancer diagnosis and treatment. Curr Oncol Rep 2019; 21: 41
    CrossrefPubMedSearch in Google Scholar
  • 47 Benjamin ER, Dilektasli E, Haltmeier T. et al. The effects of body mass index on complications and mortality after emergency abdominal operations: The obesity paradox. Am J Surg 2017; 214: 899-903.
    CrossrefPubMedSearch in Google Scholar
  • 48 Horowitz NS, Wright AA. Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies. Gynecol Oncol 2015; 138: 201-206
    CrossrefPubMedSearch in Google Scholar
  • 49 Hanna RK, Poniewierski MS, Laskey RA. et al. Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer. Gynecol Oncol 2013; 129: 74-80
    CrossrefPubMedSearch in Google Scholar
  • 50 Au-Yeung G, Webb PM, DeFazio A. et al. Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS). Gynecol Oncol 2014; 133: 16-22
    CrossrefPubMedSearch in Google Scholar
  • 51 Griggs JJ, Mangu PB, Anderson H. et al. Appropriate chemotherapy dosing for obese adult patients with cancer: American society of clinical oncology clinical practice guideline. J Clin Oncol 2012; 30: 1553-1561
    CrossrefPubMedSearch in Google Scholar
  • 52 Furlanetto J, Eiermann W, Marmé F. et al. Higher rate of severe toxicities in obese patients receiving dose-dense (dd) chemotherapy according to unadjusted body surface area: Results of the prospectively randomized GAIN study. Ann Oncol 2016; 27: 2053-2059
    CrossrefPubMedSearch in Google Scholar
  • 53 Slaughter KN, Thai T, Penaroza S. et al. Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based chemotherapy in epithelial ovarian cancer. Gynecol Oncol 2014; 133: 11-15
    CrossrefPubMedSearch in Google Scholar
  • 54 Artaç M, Korkmaz L, Coşkun H. et al. Bevacuzimab may be less effective in obese metastatic colorectal cancer patients. J Gastrointest Cancer 2019; 50: 214-220
    CrossrefPubMedSearch in Google Scholar
  • 55 Richtig G, Hoeller C, Wolf M. , et al. Body mass index may predict the response to ipilimumab in metastatic melanoma: an observational multicentre study. PLoS One 2018; 13: e0204729
    CrossrefPubMedSearch in Google Scholar
  • 56 McQuade JL, Daniel CR, Hess KR. et al. Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: A retrospective, multicohort analysis. Lancet Oncol 2018; 19: 310-322
    CrossrefPubMedSearch in Google Scholar
  • 57 Cortellini A, Bersanelli M, Buti S. et al. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable. J Immunother Cancer 2019; 7: 57
    CrossrefPubMedSearch in Google Scholar
  • 58 Zhang M, Cai H, Bao P. et al. Body mass index, waist-to-hip ratio and late outcomes: A report from the Shanghai breast cancer survival study. Sci Rep 2017; 7: 6996
    CrossrefPubMedSearch in Google Scholar
  • 59 Sirin O, Kolonin MG. Treatment of obesity as a potential complementary approach to cancer therapy. Drug Discov Today 2013; 18: 567-573
    CrossrefPubMedSearch in Google Scholar
  • 60 Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: A critical review of the evidence. Obes Sci Pract 2017; 3: 3-14
    CrossrefPubMedSearch in Google Scholar
  • 61 Schauer DP, Feigelson HS, Koebnick C. et al. Association between weight loss and the risk of cancer after bariatric surgery. Obesity (Silver Spring) 2017; 25 (Suppl. 02) S52-S57.
    CrossrefPubMedSearch in Google Scholar
  • 62 Campbell KL, Foster-Schubert KE, Alfano CM. et al. Reduced-calorie dietary weight loss, exercise, and sex hormones in postmenopausal women: Randomized controlled trial. J Clin Oncol 2012; 30: 2314-2326.
    CrossrefPubMedSearch in Google Scholar
  • 63 Monninkhof EM, Velthuis MJ, Peeters PH. , et al. Effect of exercise on postmenopausal sex hormone levels and role of body fat: A randomized controlled trial. J Clin Oncol 2009; 27: 4492-4499.
    CrossrefPubMedSearch in Google Scholar
  • 64 McTiernan A, Tworoger SS, Ulrich CM. et al. Effect of exercise on serum estrogens in postmenopausal women: A 12-month randomized clinical trial. Cancer Res 2004; 64: 2923-2928.
    CrossrefPubMedSearch in Google Scholar