Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2016

01-05-2016 | Epidemiology

Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study

Authors: Roberto Agresti, Elisabetta Meneghini, Paolo Baili, Pamela Minicozzi, Alberto Turco, Ilaria Cavallo, Francesco Funaro, Hade Amash, Franco Berrino, Elda Tagliabue, Milena Sant

Published in: Breast Cancer Research and Treatment | Issue 1/2016

Login to get access

Abstract

Obesity and metabolic syndrome are risk and prognostic factors for breast cancer (BC) and are associated with chronic inflammation. We investigated the association between distinct BC subtypes and markers of adiposity, dysmetabolisms, and inflammation. We analyzed 1779 patients with primary invasive BC treated at a single institution, for whom anthropometric and clinical-pathological data were archived. BC subtypes were classified by immunohistochemical staining of ER, PR, HER2, and Ki67, and their relations with the study markers were assessed by multinomial logistic regression. Adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated taking luminal A as reference. All subtypes more aggressive than luminal A were significantly more frequent in younger (<45 years) than older women. Before menopause, luminal B HER2-negative tumors were positively associated with large waist (OR 2.55, 95 % CI 1.53–4.24) and insulin resistance (OR 1.90, 95 % CI 1.05–3.41); luminal B HER2-positive tumors with large waist (OR 2.11, 95 % CI 1.03–4.35) and triple-negative tumors with overweight (OR 3.04, 95 % CI 1.43–6.43) and high C-reactive protein (p trend = 0.026). In postmenopausal women aged <65, luminal B HER2-negative (OR 1.94, 95 % CI 1.16–3.24) and luminal B HER2-positive tumors (OR 2.48, 95 % CI 1.16–5.27) were positively related with metabolic syndrome. Dysmetabolisms and inflammation may be related to different BC subtypes. Before menopause, triple-negative cancers were related to obesity and chronic inflammation, and aggressive luminal subtypes to abdominal adiposity. After menopause, in women aged <65 these latter subtypes were related to metabolic syndrome. Control of adiposity and dysmetabolism can reduce the risk of aggressive BC subtypes, improving the prognosis.
Literature
1.
go back to reference Sørlie T (2004) Molecular portraits of breast cancer: tumor subtypes as distinct disease entities. Eur J Cancer 40(18):2667–2675CrossRefPubMed Sørlie T (2004) Molecular portraits of breast cancer: tumor subtypes as distinct disease entities. Eur J Cancer 40(18):2667–2675CrossRefPubMed
2.
go back to reference Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747. doi:10.1093/annonc/mdr304 CrossRefPubMedPubMedCentral Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, Panel members (2011) Strategies for subtypes—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22:1736–1747. doi:10.​1093/​annonc/​mdr304 CrossRefPubMedPubMedCentral
3.
go back to reference Minicozzi P, Bella F, Toss A, Giacomin A, Fusco M, Zarcone M et al (2013) Relative and disease-free survival for breast cancer in relation to subtype: a population-based study. J Cancer Res Clin Oncol 139(9):1569–1577. doi:10.1007/s00432-013-1478-1 CrossRefPubMed Minicozzi P, Bella F, Toss A, Giacomin A, Fusco M, Zarcone M et al (2013) Relative and disease-free survival for breast cancer in relation to subtype: a population-based study. J Cancer Res Clin Oncol 139(9):1569–1577. doi:10.​1007/​s00432-013-1478-1 CrossRefPubMed
4.
go back to reference Ribelles N, Perez-Villa L, Jerez JM, Pajares B, Vicioso L, Jimenez B et al (2013) Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Res 15(5):R98CrossRefPubMedPubMedCentral Ribelles N, Perez-Villa L, Jerez JM, Pajares B, Vicioso L, Jimenez B et al (2013) Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Res 15(5):R98CrossRefPubMedPubMedCentral
8.
go back to reference Vona-Davis L, Howard-McNatt M, Rose DP (2007) Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev 8(5):395–408CrossRefPubMed Vona-Davis L, Howard-McNatt M, Rose DP (2007) Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev 8(5):395–408CrossRefPubMed
11.
go back to reference Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51CrossRefPubMed Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Madarnas Y et al (2002) Fasting insulin and outcome in early-stage breast cancer: results of a prospective cohort study. J Clin Oncol 20(1):42–51CrossRefPubMed
12.
go back to reference Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124(3):698–712. doi:10.1002/ijc.23943 CrossRefPubMed Suzuki R, Orsini N, Saji S, Key TJ, Wolk A (2009) Body weight and incidence of breast cancer defined by estrogen and progesterone receptor status—a meta-analysis. Int J Cancer 124(3):698–712. doi:10.​1002/​ijc.​23943 CrossRefPubMed
13.
go back to reference Ritte R, Lukanova A, Berrino F, Dossus L, Tjønneland A, Olsen A et al (2012) Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res 14(3):R76CrossRefPubMedPubMedCentral Ritte R, Lukanova A, Berrino F, Dossus L, Tjønneland A, Olsen A et al (2012) Adiposity, hormone replacement therapy use and breast cancer risk by age and hormone receptor status: a large prospective cohort study. Breast Cancer Res 14(3):R76CrossRefPubMedPubMedCentral
14.
go back to reference Fagherazzi G, Chabbert-Buffet N, Fabre A, Guillas G, Boutron-Ruault MC, Mesrine S et al (2012) Hip circumference is associated with the risk of premenopausal ER−/PR− breast cancer. Int J Obes (Lond) 36(3):431–439. doi:10.1038/ijo.2011.66 CrossRef Fagherazzi G, Chabbert-Buffet N, Fabre A, Guillas G, Boutron-Ruault MC, Mesrine S et al (2012) Hip circumference is associated with the risk of premenopausal ER−/PR− breast cancer. Int J Obes (Lond) 36(3):431–439. doi:10.​1038/​ijo.​2011.​66 CrossRef
20.
go back to reference Baili P, Torresani M, Agresti R, Rosito G, Daidone MG, Veneroni S et al (2015) A breast cancer clinical registry in an Italian comprehensive cancer center: an instrument for descriptive, clinical, and experimental research. Tumori 101(4):440–446. doi:10.5301/tj.5000341 CrossRefPubMed Baili P, Torresani M, Agresti R, Rosito G, Daidone MG, Veneroni S et al (2015) A breast cancer clinical registry in an Italian comprehensive cancer center: an instrument for descriptive, clinical, and experimental research. Tumori 101(4):440–446. doi:10.​5301/​tj.​5000341 CrossRefPubMed
21.
go back to reference UICC (2009) TNM: Classificazione dei Tumori Maligni, Settima Edizione. Raffaello Cortina Editore, Milano UICC (2009) TNM: Classificazione dei Tumori Maligni, Settima Edizione. Raffaello Cortina Editore, Milano
22.
go back to reference WHO (2005) ICDO-3: classificazione Internazionale delle Malattie per l’Oncologia-Terza Edizione. Inferenze Scarl, Milano WHO (2005) ICDO-3: classificazione Internazionale delle Malattie per l’Oncologia-Terza Edizione. Inferenze Scarl, Milano
23.
go back to reference Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S et al (2010) American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer. J Clin Oncol 28(16):2784–2795. doi:10.1200/JCO.2009.25.6529 CrossRefPubMedPubMedCentral Hammond ME, Hayes DF, Dowsett M, Allred DC, Hagerty KL, Badve S et al (2010) American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Immunohistochemical Testing of Estrogen and Progesterone Receptors in Breast Cancer. J Clin Oncol 28(16):2784–2795. doi:10.​1200/​JCO.​2009.​25.​6529 CrossRefPubMedPubMedCentral
25.
go back to reference Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefPubMed Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al (2009) Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120:1640–1645CrossRefPubMed
27.
29.
go back to reference Cotterchio M, Kreiger N, Theis B, Sloan M, Bahl S (2003) Hormonal factors and the risk of breast cancer according to estrogen- and progesterone-receptor subgroup. Cancer Epidemiol Biomark Prev 12:1053–1060 Cotterchio M, Kreiger N, Theis B, Sloan M, Bahl S (2003) Hormonal factors and the risk of breast cancer according to estrogen- and progesterone-receptor subgroup. Cancer Epidemiol Biomark Prev 12:1053–1060
31.
32.
go back to reference Lahmann PH, Hoffmann K, Allen N, van Gils CH, Khaw KT, Tehard B et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 111(5):762–771CrossRefPubMed Lahmann PH, Hoffmann K, Allen N, van Gils CH, Khaw KT, Tehard B et al (2004) Body size and breast cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Int J Cancer 111(5):762–771CrossRefPubMed
33.
go back to reference Muti P, Stanulla M, Micheli A, Krogh V, Freudenheim JL, Yang J et al (2000) Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy). Cancer Causes Control 11(8):721–730CrossRefPubMed Muti P, Stanulla M, Micheli A, Krogh V, Freudenheim JL, Yang J et al (2000) Markers of insulin resistance and sex steroid hormone activity in relation to breast cancer risk: a prospective analysis of abdominal adiposity, sebum production, and hirsutism (Italy). Cancer Causes Control 11(8):721–730CrossRefPubMed
36.
go back to reference Chan DS, Bandera EV, Greenwood DC, Norat T (2015) Circulating C-reactive protein and breast cancer risk-systematic literature review and meta-analysis of prospective cohort studies. Cancer Epidemiol Biomark Prev 24(10):1439–1449. doi:10.1158/1055-9965.EPI-15-0324 CrossRef Chan DS, Bandera EV, Greenwood DC, Norat T (2015) Circulating C-reactive protein and breast cancer risk-systematic literature review and meta-analysis of prospective cohort studies. Cancer Epidemiol Biomark Prev 24(10):1439–1449. doi:10.​1158/​1055-9965.​EPI-15-0324 CrossRef
37.
go back to reference Han Y, Mao F, Wu Y, Fu X, Zhu X, Zhou S et al (2011) Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis. Int J Biol Markers 26(4):209–215. doi:10.5301/JBM.2011.8872 PubMed Han Y, Mao F, Wu Y, Fu X, Zhu X, Zhou S et al (2011) Prognostic role of C-reactive protein in breast cancer: a systematic review and meta-analysis. Int J Biol Markers 26(4):209–215. doi:10.​5301/​JBM.​2011.​8872 PubMed
39.
go back to reference Siemes C, Visser LE, Coebergh JW, Splinter TA, Witteman JC, Uitterlinden AG et al (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24(33):5216–5222CrossRefPubMed Siemes C, Visser LE, Coebergh JW, Splinter TA, Witteman JC, Uitterlinden AG et al (2006) C-reactive protein levels, variation in the C-reactive protein gene, and cancer risk: the Rotterdam Study. J Clin Oncol 24(33):5216–5222CrossRefPubMed
40.
Metadata
Title
Association of adiposity, dysmetabolisms, and inflammation with aggressive breast cancer subtypes: a cross-sectional study
Authors
Roberto Agresti
Elisabetta Meneghini
Paolo Baili
Pamela Minicozzi
Alberto Turco
Ilaria Cavallo
Francesco Funaro
Hade Amash
Franco Berrino
Elda Tagliabue
Milena Sant
Publication date
01-05-2016
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2016
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-016-3802-3

Other articles of this Issue 1/2016

Breast Cancer Research and Treatment 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine