Obesity in Gynecologic Oncology

Heinz Kölbl; Thomas Bartl

doi:10.1055/a-1124-7139

Geburtshilfe und Frauenheilkunde, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2020; 80(12): 1205-1211
DOI: 10.1055/a-1124-7139

GebFra Science

Review/Übersicht

Obesity in Gynecologic Oncology

Artikel in mehreren Sprachen: English | deutsch

Heinz Kölbl

Klinische Abteilung für Allgemeine Gynäkologie und Gynäkologische Onkologie, Universitätsklinik für Frauenheilkunde, Medizinische Universität Wien, Wien, Austria

,

Thomas Bartl

Klinische Abteilung für Allgemeine Gynäkologie und Gynäkologische Onkologie, Universitätsklinik für Frauenheilkunde, Medizinische Universität Wien, Wien, Austria

› Institutsangaben

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.

Key words

obesity - gynecological malignancies - BMI

Volltext

Referenzen

References/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
2 Berghöfer A, Pischon T, Reinhold T. et al. Obesity prevalence from a European perspective: a systematic review. BMC Public Health 2008; 8: 200 doi:10.1186/1471-2458-8-200
3 Prammer-Waldhör M. Jahrbuch der Gesundheitsstatistik, Wien: Statistik Austria 2019. Accessed September 29, 2020 at: https://www.statistik.at/web_de/services/publikationen/4/index.html?includePage=detailedView&sectionName=Gesundheit&pubId=543
4 Vucenik I, Stains JP. Obesity and cancer risk: evidence, mechanisms, and recommendations. Ann N Y Acad Sci 2012; 1271: 37-43 doi:10.1111/j.1749-6632.2012.06750.x
5 Laviano A, Koverech A, Mari A. Cachexia: clinical features when inflammation drives malnutrition. Proc Nutr Soc 2015; 74: 348-354 doi:10.1017/S0029665115000117
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 doi:10.1016/j.cell.2011.08.034
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 doi:10.1038/nm.2002
8 McNelis JC, Olefsky JM. Macrophages, immunity, and metabolic disease. Immunity 2014; 41: 36-48 doi:10.1016/j.immuni.2014.05.010
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 doi:10.1172/jci19246
10 Font-Burgada J, Sun B, Karin M. Obesity and Cancer: The Oil that Feeds the Flame. Cell Metab 2016; 23: 48-62 doi:10.1016/j.cmet.2015.12.015
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 doi:10.1016/j.cmet.2007.09.011
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 doi:10.1074/jbc.M101521200
13 Nielsen S, Guo Z, Johnson CM. et al. Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113: 1582-1588 doi:10.1172/jci21047
14 Yang Y, Ju D, Zhang M. et al. Interleukin-6 stimulates lipolysis in porcine adipocytes. Endocrine 2008; 33: 261-269 doi:10.1007/s12020-008-9085-7
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 doi:10.1158/1078-0432.ccr-06-0912
16 Dalamaga M, Diakopoulos KN, Mantzoros CS. The role of adiponectin in cancer: a review of current evidence. Endocr Rev 2012; 33: 547-594 doi:10.1210/er.2011-1015
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 doi:10.1016/j.diabet.2007.09.004
18 Fasshauer M, Bluher M. Adipokines in health and disease. Trends Pharmacol Sci 2015; 36: 461-470 doi:10.1016/j.tips.2015.04.014
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 doi:10.1016/j.steroids.2014.08.006
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 doi:10.1111/cen.12768
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 doi:10.1002/ijc.11529
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 doi:10.1055/s-0034-1395606
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 doi:10.1158/1055-9965.epi-07-2567
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 doi:10.1200/JCO.2016.69.4638
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 doi:10.1016/j.ajog.2016.01.175
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 J Med 2003; 348: 1625-1638 doi:10.1056/NEJMoa021423
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 doi:10.1002/ijc.28926
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 doi:10.1002/ijc.23943
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 doi:10.1001/jamaoncol.2015.1546
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 doi:10.1007/s10549-012-2339-3
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 doi:10.1001/jamaoncol.2018.1771
32 Jiralerspong S, Goodwin PJ. Obesity and Breast Cancer Prognosis: Evidence, Challenges, and Opportunities. J Clin Oncol 2016; 34: 4203-4216 doi:10.1200/jco.2016.68.4480
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 doi:10.1530/ERC-12-0395
34 Hew KE, Bakhru A, Harrison E. et al. The Effect of Obesity on the Time to Recurrence in Ovarian Cancer: A Retrospective Study. Clinical Ovarian and Other Gynecologic Cancer 2013; 6: 31-35 doi:10.1016/j.cogc.2014.02.002
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 doi:10.1200/JCO.2019.37.15_suppl.e17130
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 doi:10.1136/ijgc-2019-001187
37 Poorolajal J, Jenabi E. The association between BMI and cervical cancer risk: a meta-analysis. Eur J Cancer Prev 2016; 25: 232-238 doi:10.1097/cej.0000000000000164
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 doi:10.1038/oby.2008.480
39 Lacey 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 doi:10.1002/cncr.11567
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 doi:10.1097/01.ogx.0000180866.62409.01
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 doi:10.1200/JCO.2017.75.3442
42 Ri M, Aikou S, Seto Y. Obesity as a surgical risk factor. Ann Gastroenterol Surg 2017; 2: 13-21 doi:10.1002/ags3.12049
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 doi:10.1016/j.ygyno.2015.09.020
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 doi:10.1111/1471-0528.13585
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 doi:10.1097/AOG.0b013e3181863280
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 doi:10.1007/s11912-019-0787-1
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 doi:10.1016/j.amjsurg.2017.01.023
48 Horowitz NS, Wright AA. Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies. Gynecol Oncol 2015; 138: 201-206 doi:10.1016/j.ygyno.2015.04.002
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 doi:10.1016/j.ygyno.2012.12.017
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 doi:10.1016/j.ygyno.2014.01.030
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 doi:10.1200/jco.2011.39.9436
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 doi:10.1093/annonc/mdw315
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 doi:10.1016/j.ygyno.2014.01.031
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 doi:10.1007/s12029-017-0047-2
55 Richtig G, Hoeller C, Wolf M. et al. Body mass index may predict the response to ipilimumab in metastatic melanoma: An observational multi-centre study. PLoS One 2018; 13: e0204729 doi:10.1371/journal.pone.0204729
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 doi:10.1016/S1470-2045(18)30078-0
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 doi:10.1186/s40425-019-0527-y
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 doi:10.1038/s41598-017-07320-7
59 Sirin O, Kolonin MG. Treatment of obesity as a potential complementary approach to cancer therapy. Drug Discov Today 2013; 18: 567-573 doi:10.1016/j.drudis.2012.05.008
60 Mehta A, Marso SP, Neeland IJ. Liraglutide for weight management: a critical review of the evidence. Obes Sci Pract 2017; 3: 3-14 doi:10.1002/osp4.84
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 doi:10.1002/oby.22002
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 doi:10.1200/jco.2011.37.9792
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 doi:10.1200/jco.2008.19.7459
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 doi:10.1158/0008-5472.can-03-3393