The Association between Obesity and Premenopausal Breast Cancer According to Intrinsic Subtypes – a Systematic Review

Abstract

Introduction Obesity is a well-established risk factor for postmenopausal hormone-receptor positive breast cancer. The relationship between premenopausal breast cancer intrinsic subtypes and obesity is not completely elucidated; therefore, this systematic review was conducted to give an overview about the existing evidence.

Methods This review followed the PRISMA Statement for Systematic Reviews and Meta-analyses. Full electronic search was conducted in PubMed and Orbis for articles published in English between January 2008 and June 2018. The literature search was performed in June 2018 using search strings that combined the Medical Subject Headings (MeSH terms) keywords and/or text words in any field were used: “body mass index” (BMI) OR obesity OR overweight AND premenopausal breast cancer.

Results 391 articles were found to be eligible, of which ultimately 21 were included comprising a total of 55 580 breast cancer patients. 45% were case-control studies, 35% were single cohort studies, 15% were cohort studies, two were cross-sectional studies, one was a multicenter-study and one was a pooled analysis. The evidence shows a tendency for an increased risk for the more aggressive triple negative breast cancer subtype in obese premenopausal women and a decreased risk for less aggressive tumor subtypes such as the luminal A subtype. The evidence is limited by small sample sizes for triple negative and HER2-positive subtypes in severely obese patients.

Conclusion Higher BMI might influence aggressive tumor characteristics among premenopausal women and has divergent impacts on the risk of different breast cancer subtypes. Further research is needed to confirm these results and to evaluate potential pathophysiologic mechanisms for the relationship between obesity and aggressive premenopausal breast cancer subtypes.

Zusammenfassung

Einleitung Übergewicht ist ein bekannter Risikofaktor für postmenopausalen hormonrezeptorpositiven Brustkrebs. Der Zusammenhang zwischen prämenopausalen intrinsischen Mammakarzinom-Subtypen und Übergewicht ist aber noch nicht ganz geklärt. Es wurde daher eine systematische Literaturrecherche durchgeführt, um einen Überblick der existierenden Evidenz zu bekommen.

Methoden Diese Literaturrecherche wurde gemäß den PRISMA-Vorgaben zu systematischen Übersichten und Metaanalysen durchgeführt. In den Datenbanken PubMed und Orbis wurde eine elektronische Suche nach englischsprachigen Artikeln, die zwischen Januar 2008 und Juni 2018 veröffentlicht wurden, durchgeführt. Die Literaturrecherche wurde im Juni 2018 vorgenommen unter Verwendung einer Kombination von MeSH (Medical Subject Headings) Suchbegriffen und „und/oder“ Worten in allen Feldern wie folgt: „body mass index“ (BMI) OR „obesity“ OR „overweight“ AND „premenopausal breast cancer“.

Ergebnisse Insgesamt fanden sich 391 geeignete Publikationen, von denen schließlich 21 Studien, die insgesamt 55 580 Brustkrebspatientinnen einschlossen, ausgewählt wurden. Von den ausgewählten Studien waren 45% Fallkontrollstudien, 35% einfache Kohortenstudien und 15% Kohortenstudien. Es waren auch 2 Querschnittsstudien, eine multizentrische Studie und eine gepoolte Analyse darunter. Die durch die Recherche gewonnene Evidenz zeigt, dass adipöse prämenopausale Frauen ein tendenziell höheres Risiko für aggressivere triple-negative Brustkrebs-Subtypen und ein geringeres Risiko für weniger aggressive Subtypen wie Luminal-A-Tumoren aufweisen. Die kleine Fallzahl an stark adipösen Patientinnen mit triple-negativen und HER2-positiven Subtypen schränkt jedoch die Aussagekraft der Evidenz ein.

Schlussfolgerung Ein höherer BMI könnte einen Einfluss auf aggressive Tumoreigenschaften bei prämenopausalen Frauen haben und hat unterschiedliche Auswirkungen auf das Risiko für verschiedene Brustkrebs-Subtypen. Es werden weitere Studien benötigt, um diese Ergebnisse zu bestätigen und die möglichen pathophysiologischen Mechanismen für die Beziehung zwischen Adipositas und aggressiven prämenopausalen Brustkrebs-Subtypen zu ermitteln.

Key words

hormone receptor - premenopause - breast neoplasms - receptors - obesity - risk factors

Schlüsselwörter

Hormonrezeptor - Prämenopause - Brusttumoren - Rezeptoren - Adipositas - Risikofaktoren

Publication History

Received: 16 October 2019
Received: 06 April 2020

Accepted: 27 April 2020

Article published online:
17 June 2020

• References

• 1 World Health Organization (WHO). Obesity – Preventing and Managing the Global Epidemic: Report of a WHO Consultation. Geneva, Switzerland: World Health Organization; 2000: Online: https://apps.who.int/iris/handle/10665/42330 last access: 02.09.2019
• 2 Renehan AG, Tyson M, Egger M. et al. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 2008; 371: 569-578 doi:10.1016/S0140-6736(08)60269-X
• 3 Renehan AG, Soerjomataram I, Tyson M. et al. Incident cancer burden attributable to excess body mass index in 30 European countries. Int J Cancer 2010; 126: 692-702 doi:10.1002/ijc.24803
• 4 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 2013; 348: 1625-1638 doi:10.1056/NEJMoa021423
• 5 Abarca-Gómez L, Abdeen ZA, Hamid ZA. et al. Worldwide trends in body-mass index, underweight, overweight and obesity from 1975 to 2016: a pooled analysis of 2416 population-based measurement studies in 128.9 children, adolescents and adults. Lancet 2017; 390: 2627-2642 doi:10.1016/S0140-6736(17)32129-3
• 6 Mensink GBM, Schienkiewitz A, Haftenberger M. et al. Übergewicht und Adipositas in Deutschland: Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS1). Bundesgesundheitsblatt 2013; 56: 795-801 doi:10.1007/s00103-013-1669-6
• 7 Munsell MF, Sprague BL, Berry DA. et al. Body mass index and breast cancer risk according to postmenopausal estrogen-progestin use and hormone receptor status. Epidemiol Rev 2014; 36: 114-136 doi:10.1093/epirev/mxt010
• 8 Berclaz G, Li S, Price KN. et al. Body mass index as a prognostic feature in operable breast cancer: the International Breast Cancer Study Group experience. Ann Oncol 2004; 15: 875-884 doi:10.1093/annonc/mdh222
• 9 Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 2004; 4: 579-591 doi:10.1038/nrc1408
• 10 Kawai M, Minami Y, Nishino Y. et al. Body mass index and survival after breast cancer diagnosis in Japanese women. BMC Cancer 2012; 12: 149 doi:10.1186/1471-2407-12-149
• 11 Biglia N, Peano E, Sgandurra P. et al. Body mass index (BMI) and breast cancer: impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecol Endocrinol 2013; 29: 263-267 doi:10.3109/09513590.2012.736559
• 12 Daling JR, Malone KE, Doody DR. et al. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 2001; 92: 720-729 doi:10.1002/1097-0142(20010815)92:4<720::aid-cncr1375>3.0.co;2-t
• 13 Yanai A, Miyagawa Y, Murase K. et al. Influence of body mass index on clinicopathological factors including estrogen receptor, progesterone receptor, and Ki67 expression levels in breast cancers. Int J Clin Oncol 2014; 19: 467-472 doi:10.1007/s10147-013-0585-y
• 14 Viale G. The current state of breast cancer classification. Ann Oncol 2012; 23 (Suppl. 10) x207-x210 doi:10.1093/annonc/mds326
• 15 Kreipe HH. Translationale Forschung und Diagnostik beim Mammakarzinom. Pathologe 2012; 33 (Suppl. 02) 282-290 doi:10.1007/s00292-012-1645-1
• 16 Moher D, Liberati A, Tetzlaff J. et al. PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009; 339: b2535 doi:10.1136/bmj.b2535
• 17 John EM, Sangaramoorthy M, Phipps AI. et al. Adult body size, hormone receptor status, and premenopausal breast cancer risk in a multiethnic population: the San Francisco Bay Area breast cancer study. Am J Epidemiol 2011; 173: 201-216 doi:10.1093/aje/kwq345
• 18 Berstad P, Coates RJ, Bernstein L. et al. A case-control study of body mass index and breast cancer risk in white and African-American women. Cancer Epidemiol Biomarkers Prev 2010; 19: 1532-1544 doi:10.1158/1055-9965.EPI-10-0025
• 19 Bandera EV, Chandran U, Zirpoli G. et al. Body fatness and breast cancer risk in women of African ancestry. BMC Cancer 2013; 13: 475 doi:10.1186/1471-2407-13-475
• 20 Kawai M, Kakugawa Y, Nishino Y. et al. Anthropometric factors, physical activity, and breast cancer risk in relation to hormone receptor and menopausal status in Japanese women: a case-control study. Cancer Causes Control 2013; 24: 1033-1044 doi:10.1007/s10552-013-0181-5
• 21 Wang F, Liu L, Cui S. et al. Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention. Oncologist 2017; 22: 1431-1443 doi:10.1634/theoncologist.2017-0148
• 22 White AJ, Nichols HB, Bradshaw PT. et al. Overall and central adiposity and breast cancer risk in the Sister Study. Cancer 2015; 121: 3700-3708 doi:10.1002/cncr.29552
• 23 Fagherazzi G, Chabbert-Buffet N, Fabre A. et al. Hip circumference is associated with the risk of premenopausal ER-/PR- breast cancer. Int J Obes 2012; 36: 431-439 doi:10.1038/ijo.2011.66
• 24 Nagrani R, Mhatre S, Rajaraman P. et al. Central obesity increases risk of breast cancer irrespective of menopausal and hormonal receptor status in women of South Asian Ethnicity. Eur J Cancer 2016; 66: 153-161 doi:10.1016/j.ejca.2016.07.022
• 25 Sahin S, Erdem GU, Karatas F. et al. The association between body mass index and immunohistochemical subtypes in breast cancer. Breast 2017; 32: 227-236 doi:10.1016/j.breast.2016.09.019
• 26 Nattenmüller CJ, Kriegsmann M, Sookthai D. et al. Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study. BMC Cancer 2018; 18: 616 doi:10.1186/s12885-018-4548-6
• 27 Yang XR, Sherman ME, Rimm DL. et al. Differences in risk factors for breast cancer molecular subtypes in a population-based study. Cancer Epidemiol Biomarkers Prev 2007; 16: 439-443 doi:10.1158/1055-9965.EPI-06-0806
• 28 Chen FY, Ou HY, Wang SM. et al. Associations between body mass index and molecular subtypes as well as other clinical characteristics of breast cancer in Chinese women. Ther Clin Risk Manag 2013; 9: 131-137 doi:10.2147/TCRM.S41203
• 29 Chen L, Cook LS, Tang M-TC. et al. Body mass index and risk of luminal, HER2-overexpressing, and triple negative breast cancer. Breast Cancer Res Treat 2016; 157: 545-554 doi:10.1007/s10549-016-3825-9
• 30 Millikan RC, Newman B, Tse CK. et al. Epidemiology of basal-like breast cancer. Breast Cancer Res Treat 2008; 109: 123-139 doi:10.1007/s10549-007-9632-6
• 31 Agresti R, Meneghini E, Baili P. et al. Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study. Breast Cancer Res Treat 2016; 157: 179-189 doi:10.1007/s10549-016-3802-3
• 32 Lara-Medina F, Pérez-Sánchez V, Saavedra-Pérez D. et al. Triple-negative breast cancer in Hispanic patients: high prevalence, poor prognosis, and association with menopausal status, body mass index, and parity. Cancer 2011; 117: 3658-3669 doi:10.1002/cncr.25961
• 33 Lin NU, Vanderplas A, Hughes ME. et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer 2012; 118: 5463-5472 doi:10.1002/cncr.27581
• 34 Li H, Sun X, Miller E. et al. BMI, reproductive factors, and breast cancer molecular subtypes: A case-control study and meta-analysis. J Epidemiol 2017; 27: 143-151 doi:10.1016/j.je.2016.05.002
• 35 Yang XR, Chang-Claude J, Goode EL. et al. Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies. J Natl Cancer Inst 2011; 103: 250-263 doi:10.1093/jnci/djq526
• 36 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
• 37 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
• 38 Schoemaker MJ, Nichols HB, Wright LB. et al. Premenopausal Breast Cancer Collaborative Group. 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
• 39 McTiernan A, Rajan KB, Tworoger SS. et al. Adiposity and sex hormones in postmenopausal breast cancer survivors. J Clin Oncol 2003; 21: 1961-1966 doi:10.1200/JCO.2003.07.057
• 40 Cleary MP, Grossmann ME. Minireview: Obesity and breast cancer: the estrogen connection. Endocrinology 2009; 150: 2537-2542 doi:10.1210/en.2009-0070
• 41 Key TJ, Pike MC. The role of oestrogens and progestagens in the epidemiology and prevention of breast cancer. Eur J Cancer Clin Oncol 1988; 24: 29-43
• 42 Key TJ, Appleby PN, Reeves GK. et al. Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies. Lancet Oncol 2013; 14: 1009-1019 doi:10.1016/S1470-2045(13)70301-2