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Published in: Breast Cancer Research and Treatment 3/2013

01-04-2013 | Epidemiology

Fasting blood glucose and long-term prognosis of non-metastatic breast cancer: a cohort study

Authors: Paolo Contiero, Franco Berrino, Giovanna Tagliabue, Antonio Mastroianni, Maria Gaetana Di Mauro, Sabrina Fabiano, Monica Annulli, Paola Muti

Published in: Breast Cancer Research and Treatment | Issue 3/2013

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Abstract

High circulating glucose has been associated with increased risk of breast cancer (BC). There may also be a link between serum glucose and prognosis in women treated for BC. We assessed the effect of peridiagnostic fasting blood glucose and body mass index (BMI) on long-term BC prognosis. We retrospectively investigated 1,261 women diagnosed and treated for stage I–III BC at the National Cancer Institute, Milan, in 1996, 1999 and 2000. Data on blood tests and follow-up were obtained by linking electronic archives, with follow-up to end of 2009. Multivariate Cox modelling estimated hazard ratios (HR) with 95 % confidence intervals (CI) for distant metastasis, recurrence and death (all causes) in relation to categorized peridiagnostic fasting blood glucose and BMI. Mediation analysis investigated whether blood glucose mediated the BMI-breast cancer prognosis association. The risks of distant metastasis were significantly higher for all other quintiles compared to the lowest glucose quintile (reference <87 mg/dL) (respective HRs: 1.99 95 % CI 1.23–3.24, 1.85 95 % CI 1.14–3.0, 1.73 95 % CI 1.07–2.8, and 1.91 95 % CI 1.15–3.17). The risk of recurrence was significantly higher for all other glucose quintiles compared to the first. The risk of death was significantly higher than reference in the second, fourth and fifth quintiles. Women with BMI ≥ 25 kg/m2 had significantly greater risks of recurrence and distant metastasis than those with BMI < 25 kg/m2, irrespective of blood glucose. The increased risks remained invariant over a median follow-up of 9.5 years. Mediation analysis indicated that glucose and BMI had independent effects on BC prognosis. Peridiagnostic high fasting glucose and obesity predict worsened short- and long-term outcomes in BC patients. Maintaining healthy blood glucose levels and normal weight may improve prognosis.
Literature
2.
go back to reference Koroljow S (1962) Two cases of malignant tumors with metastases apparently treated successfully with hypoglycemic coma. Psychiatr Q 36:261–270PubMedCrossRef Koroljow S (1962) Two cases of malignant tumors with metastases apparently treated successfully with hypoglycemic coma. Psychiatr Q 36:261–270PubMedCrossRef
3.
go back to reference Carroll KK (1977) Dietary factors in hormone-dependent cancers. Curr Concepts Nutr 6:25–40PubMed Carroll KK (1977) Dietary factors in hormone-dependent cancers. Curr Concepts Nutr 6:25–40PubMed
4.
go back to reference Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schünemann HJ, Ram M, Freudenheim JL, Sieri S, Trevisan M, Berrino F (2002) Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 11(11):1361–1368PubMed Muti P, Quattrin T, Grant BJ, Krogh V, Micheli A, Schünemann HJ, Ram M, Freudenheim JL, Sieri S, Trevisan M, Berrino F (2002) Fasting glucose is a risk factor for breast cancer: a prospective study. Cancer Epidemiol Biomarkers Prev 11(11):1361–1368PubMed
5.
go back to reference Sieri S, Muti P, Claudia A, Berrino F, Pala V, Grioni S, Abagnato CA, Blandino G, Contiero P, Schunemann HJ, Krogh V (2012) Prospective study on the role of glucose metabolism in breast cancer occurrence. Int J Cancer 130(4):921–929PubMedCrossRef Sieri S, Muti P, Claudia A, Berrino F, Pala V, Grioni S, Abagnato CA, Blandino G, Contiero P, Schunemann HJ, Krogh V (2012) Prospective study on the role of glucose metabolism in breast cancer occurrence. Int J Cancer 130(4):921–929PubMedCrossRef
6.
go back to reference Holmes MD, Liu S, Hankinson SE, Colditz GA, Hunter DJ, Willett WC (2004) Dietary carbohydrates, fiber, and breast cancer risk. Am J Epidemiol 159(8):732–739PubMedCrossRef Holmes MD, Liu S, Hankinson SE, Colditz GA, Hunter DJ, Willett WC (2004) Dietary carbohydrates, fiber, and breast cancer risk. Am J Epidemiol 159(8):732–739PubMedCrossRef
7.
go back to reference Miao Jonasson J, Cederholm J, Eliasson B, Zethelius B, Eeg-Olofsson K, Gudbjörnsdottir S (2012) HbA1C and cancer risk in patients with type 2 diabetes–a nationwide population-based prospective cohort study in Sweden. PLoS One 7(6):e38784. doi:10.1371/journal.pone.0038784 PubMedCrossRef Miao Jonasson J, Cederholm J, Eliasson B, Zethelius B, Eeg-Olofsson K, Gudbjörnsdottir S (2012) HbA1C and cancer risk in patients with type 2 diabetes–a nationwide population-based prospective cohort study in Sweden. PLoS One 7(6):e38784. doi:10.​1371/​journal.​pone.​0038784 PubMedCrossRef
8.
go back to reference Garber K (2004) Energy boost: the Warburg effect returns in a new theory of cancer. J Natl Cancer Inst 96(24):1805–1806PubMedCrossRef Garber K (2004) Energy boost: the Warburg effect returns in a new theory of cancer. J Natl Cancer Inst 96(24):1805–1806PubMedCrossRef
9.
10.
go back to reference Sun Y (1990) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 8(6):583–599PubMedCrossRef Sun Y (1990) Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med 8(6):583–599PubMedCrossRef
11.
go back to reference Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T (1996) Oxidative damage to DNA in diabetes mellitus. Lancet 347:444–445PubMedCrossRef Dandona P, Thusu K, Cook S, Snyder B, Makowski J, Armstrong D, Nicotera T (1996) Oxidative damage to DNA in diabetes mellitus. Lancet 347:444–445PubMedCrossRef
12.
go back to reference Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202(3):654–662PubMedCrossRef Macheda ML, Rogers S, Best JD (2005) Molecular and cellular regulation of glucose transporter (GLUT) proteins in cancer. J Cell Physiol 202(3):654–662PubMedCrossRef
13.
go back to reference Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A, Brys M (2012) Expression of GLUT1 and GLUT3 Glucose Transporters in Endometrial and Breast Cancers. Pathol Oncol Res 18(3):721–728PubMedCrossRef Krzeslak A, Wojcik-Krowiranda K, Forma E, Jozwiak P, Romanowicz H, Bienkiewicz A, Brys M (2012) Expression of GLUT1 and GLUT3 Glucose Transporters in Endometrial and Breast Cancers. Pathol Oncol Res 18(3):721–728PubMedCrossRef
14.
go back to reference Zeng L, Biernacka KM, Holly JM, Jarrett C, Morrison AA, Morgan A, Winters ZE, Foulstone EJ, Shield JP, Perks CM (2010) Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocr Relat Cancer 17(2):539–551PubMedCrossRef Zeng L, Biernacka KM, Holly JM, Jarrett C, Morrison AA, Morgan A, Winters ZE, Foulstone EJ, Shield JP, Perks CM (2010) Hyperglycaemia confers resistance to chemotherapy on breast cancer cells: the role of fatty acid synthase. Endocr Relat Cancer 17(2):539–551PubMedCrossRef
15.
go back to reference Pasanisi P, Berrino F, De Petris M, Venturelli E, Mastroianni A, Panico S (2006) Metabolic syndrome as a prognostic factor for breast cancer recurrences. Int J Cancer 119(1):236–238PubMedCrossRef Pasanisi P, Berrino F, De Petris M, Venturelli E, Mastroianni A, Panico S (2006) Metabolic syndrome as a prognostic factor for breast cancer recurrences. Int J Cancer 119(1):236–238PubMedCrossRef
16.
go back to reference Belle FN, Kampman E, McTiernan A, Bernstein L, Baumgartner K, Baumgartner R, Ambs A, Ballard-Barbash R, Neuhouser ML (2011) Dietary fiber, carbohydrates, glycemic index, and glycemic load in relation to breast cancer prognosis in the HEAL cohort. Cancer Epidemiol Biomarkers Prev 20(5):890–899PubMedCrossRef Belle FN, Kampman E, McTiernan A, Bernstein L, Baumgartner K, Baumgartner R, Ambs A, Ballard-Barbash R, Neuhouser ML (2011) Dietary fiber, carbohydrates, glycemic index, and glycemic load in relation to breast cancer prognosis in the HEAL cohort. Cancer Epidemiol Biomarkers Prev 20(5):890–899PubMedCrossRef
17.
go back to reference Krone CA, Ely JT (2005) Controlling hyperglycemia as an adjunct to cancer therapy. Integr Cancer Ther 4(1):25–31PubMedCrossRef Krone CA, Ely JT (2005) Controlling hyperglycemia as an adjunct to cancer therapy. Integr Cancer Ther 4(1):25–31PubMedCrossRef
18.
go back to reference Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Taylor SK, Hood N (2012) Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. J Clin Oncol 30(2):164–171PubMedCrossRef Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Taylor SK, Hood N (2012) Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. J Clin Oncol 30(2):164–171PubMedCrossRef
19.
go back to reference Contiero P, Tittarelli A, Tagliabue G, Maghini A, Fabiano S, Crosignani P, Tessandori R (2005) The EpiLink record linkage software: presentation and results of linkage test on cancer registry files. Methods Inf Med 44(1):66–71PubMed Contiero P, Tittarelli A, Tagliabue G, Maghini A, Fabiano S, Crosignani P, Tessandori R (2005) The EpiLink record linkage software: presentation and results of linkage test on cancer registry files. Methods Inf Med 44(1):66–71PubMed
20.
go back to reference Tagliabue G, Maghini A, Fabiano S, Tittarelli A, Frassoldi E, Costa E, Nobile S, Codazzi T, Crosignani P, Tessandori R, Contiero P (2006) Consistency and accuracy of diagnostic cancer codes generated by automated registration: comparison with manual registration. Popul Health Metr 4:10PubMedCrossRef Tagliabue G, Maghini A, Fabiano S, Tittarelli A, Frassoldi E, Costa E, Nobile S, Codazzi T, Crosignani P, Tessandori R, Contiero P (2006) Consistency and accuracy of diagnostic cancer codes generated by automated registration: comparison with manual registration. Popul Health Metr 4:10PubMedCrossRef
21.
go back to reference Therneau TM, Grambsch PM (2000) Testing proportional hazards. In: Modeling survival data: extending the Cox model. Springer, New York Therneau TM, Grambsch PM (2000) Testing proportional hazards. In: Modeling survival data: extending the Cox model. Springer, New York
22.
go back to reference Bellera CA, MacGrogan G, Debled M, de Lara CT, Brouste V, Mathoulin-Pélissier S (2010) Variables with time-varying effects and the Cox model: some statistical concepts illustrated with a prognostic factor study in breast cancer. BMC Med Res Methodol 10:20PubMedCrossRef Bellera CA, MacGrogan G, Debled M, de Lara CT, Brouste V, Mathoulin-Pélissier S (2010) Variables with time-varying effects and the Cox model: some statistical concepts illustrated with a prognostic factor study in breast cancer. BMC Med Res Methodol 10:20PubMedCrossRef
23.
go back to reference MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V (2002) A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 7(1):83–104PubMedCrossRef MacKinnon DP, Lockwood CM, Hoffman JM, West SG, Sheets V (2002) A comparison of methods to test mediation and other intervening variable effects. Psychol Methods 7(1):83–104PubMedCrossRef
24.
go back to reference Freedman LS, Schatzkin A (1992) Sample size for studying intermediate endpoints within intervention trails or observational studies. Am J Epidemiol 136(9):1148–1159PubMed Freedman LS, Schatzkin A (1992) Sample size for studying intermediate endpoints within intervention trails or observational studies. Am J Epidemiol 136(9):1148–1159PubMed
26.
go back to reference Ewertz M, Jensen MB, Gunnarsdóttir KÁ, Højris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S (2011) Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29(1):25–31PubMedCrossRef Ewertz M, Jensen MB, Gunnarsdóttir KÁ, Højris I, Jakobsen EH, Nielsen D, Stenbygaard LE, Tange UB, Cold S (2011) Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 29(1):25–31PubMedCrossRef
27.
go back to reference de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M, Giuliani R, Nordenskjöld B, Gutiérez J, Andersson M, Vila MM, Jakesz R, Demol J, Dewar J, Santoro A, Lluch A, Olsen S, Gelber RD, Di Leo A, Piccart-Gebhart M (2010) The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02–98 trial. Breast Cancer Res Treat 119(1):145–153PubMedCrossRef de Azambuja E, McCaskill-Stevens W, Francis P, Quinaux E, Crown JP, Vicente M, Giuliani R, Nordenskjöld B, Gutiérez J, Andersson M, Vila MM, Jakesz R, Demol J, Dewar J, Santoro A, Lluch A, Olsen S, Gelber RD, Di Leo A, Piccart-Gebhart M (2010) The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02–98 trial. Breast Cancer Res Treat 119(1):145–153PubMedCrossRef
28.
go back to reference Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–633PubMedCrossRef Protani M, Coory M, Martin JH (2010) Effect of obesity on survival of women with breast cancer: systematic review and meta-analysis. Breast Cancer Res Treat 123(3):627–633PubMedCrossRef
30.
31.
32.
go back to reference Wang H, Wang J, Liu MM, Wang D, Liu YQ, Zhao Y, Huang MM, Liu Y, Sun J, Dong GH (2012) Epidemiology of general obesity, abdominal obesity and related risk factors in urban adults from 33 communities of northeast china: the CHPSNE study. BMC Public Health 12:967PubMedCrossRef Wang H, Wang J, Liu MM, Wang D, Liu YQ, Zhao Y, Huang MM, Liu Y, Sun J, Dong GH (2012) Epidemiology of general obesity, abdominal obesity and related risk factors in urban adults from 33 communities of northeast china: the CHPSNE study. BMC Public Health 12:967PubMedCrossRef
33.
go back to reference Levy RB, Claro RM, Bandoni DH, Mondini L, Monteiro CA (2012) Availability of added sugars in Brazil: distribution, food sources and time trends. Rev Bras Epidemiol 15(1):3–12PubMedCrossRef Levy RB, Claro RM, Bandoni DH, Mondini L, Monteiro CA (2012) Availability of added sugars in Brazil: distribution, food sources and time trends. Rev Bras Epidemiol 15(1):3–12PubMedCrossRef
34.
go back to reference World Health Organization (2006) Obesity and overweight. Fact sheet number 311. World Health Organization, Geneva World Health Organization (2006) Obesity and overweight. Fact sheet number 311. World Health Organization, Geneva
Metadata
Title
Fasting blood glucose and long-term prognosis of non-metastatic breast cancer: a cohort study
Authors
Paolo Contiero
Franco Berrino
Giovanna Tagliabue
Antonio Mastroianni
Maria Gaetana Di Mauro
Sabrina Fabiano
Monica Annulli
Paola Muti
Publication date
01-04-2013
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2013
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-013-2519-9

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