Skip to main content
Top
Published in: Breast Cancer Research and Treatment 1/2014

01-11-2014 | Epidemiology

Diabetes, diabetes treatment and breast cancer prognosis

Authors: Juhua Luo, Beth Virnig, Michael Hendryx, Sijin Wen, Rowan Chelebowski, Chu Chen, Tomas Rohan, Lesley Tinker, Jean Wactawski-Wende, Lawrence Lessin, Karen Margolis

Published in: Breast Cancer Research and Treatment | Issue 1/2014

Login to get access

Abstract

The objectives of this study are to assess the impact of pre-existing diabetes and diabetes treatment on breast cancer prognosis. 8,108 women with centrally confirmed invasive breast cancer in the Women’s Health Initiative diagnosed between 1998 and 2013 were followed through the date of death or September 20, 2013. Information on diabetes and diabetes therapy were obtained via self-report and face-to-face review of current medication containers, respectively. Cox proportional hazard regression was used to estimate adjusted relative hazard ratios for overall mortality. The proportional subdistribution hazard model was used to estimate hazard ratios for breast cancer-specific mortality. Compared with women without diabetes, women with diabetes had significantly increased risk of overall mortality (HR 1.26 95 % CI 1.06–1.48), especially among those who took insulin or had longer duration of diabetes. However, diabetes was not associated with increased risk of breast cancer-specific mortality, regardless of type of treatment and duration of diabetes, despite the significant association of diabetes with unfavorable tumor characteristics. Our large prospective cohort study provides additional evidence that pre-existing diabetes increases risk of total mortality among women with breast cancer. The increased total mortality associated with diabetes was mainly driven by increased risk of dying from diseases other than breast cancer. Thus, the continuum of care for breast cancer patients with diabetes should include careful attention to CVD risk factors and other non-cancer conditions.
Appendix
Available only for authorised users
Literature
1.
go back to reference The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19:61–109CrossRef The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19:61–109CrossRef
4.
go back to reference Bayraktar S, Hernadez-Aya LF, Lei X, Meric-Bernstam F, Litton JK, Hsu L, Hortobagyi GN, Gonzalez-Angulo AM (2012) Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer 118:1202–1211. doi:10.1002/cncr.26439 PubMedCrossRefPubMedCentral Bayraktar S, Hernadez-Aya LF, Lei X, Meric-Bernstam F, Litton JK, Hsu L, Hortobagyi GN, Gonzalez-Angulo AM (2012) Effect of metformin on survival outcomes in diabetic patients with triple receptor-negative breast cancer. Cancer 118:1202–1211. doi:10.​1002/​cncr.​26439 PubMedCrossRefPubMedCentral
5.
go back to reference Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F (2011) Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res 71:4366–4372. doi:10.1158/0008-5472.CAN-10-1769 PubMedCrossRef Ben Sahra I, Regazzetti C, Robert G, Laurent K, Le Marchand-Brustel Y, Auberger P, Tanti JF, Giorgetti-Peraldi S, Bost F (2011) Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1. Cancer Res 71:4366–4372. doi:10.​1158/​0008-5472.​CAN-10-1769 PubMedCrossRef
6.
go back to reference Boyle P, Boniol M, Koechlin A, Robertson C, Valentini F, Coppens K, Fairley LL, Boniol M, Zheng T, Zhang Y, Pasterk M, Smans M, Curado MP, Mullie P, Gandini S, Bota M, Bolli GB, Rosenstock J, Autier P (2012) Diabetes and breast cancer risk: a meta-analysis. Br J Cancer. doi:10.1038/bjc.2012.414 PubMedPubMedCentral Boyle P, Boniol M, Koechlin A, Robertson C, Valentini F, Coppens K, Fairley LL, Boniol M, Zheng T, Zhang Y, Pasterk M, Smans M, Curado MP, Mullie P, Gandini S, Bota M, Bolli GB, Rosenstock J, Autier P (2012) Diabetes and breast cancer risk: a meta-analysis. Br J Cancer. doi:10.​1038/​bjc.​2012.​414 PubMedPubMedCentral
8.
go back to reference Chlebowski RT, McTiernan A, Wactawski-Wende J, Manson JE, Aragaki AK, Rohan T, Ipp E, Kaklamani VG, Vitolins M, Wallace R, Gunter M, Phillips LS, Strickler H, Margolis K, Euhus DM (2012) Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 30:2844–2852. doi:10.1200/JCO.2011.39.7505 PubMedCrossRefPubMedCentral Chlebowski RT, McTiernan A, Wactawski-Wende J, Manson JE, Aragaki AK, Rohan T, Ipp E, Kaklamani VG, Vitolins M, Wallace R, Gunter M, Phillips LS, Strickler H, Margolis K, Euhus DM (2012) Diabetes, metformin, and breast cancer in postmenopausal women. J Clin Oncol 30:2844–2852. doi:10.​1200/​JCO.​2011.​39.​7505 PubMedCrossRefPubMedCentral
10.
13.
go back to reference Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef Fine JP, Gray RJ (1999) A proportional hazards model for the subdistribution of a competing risk. J Am Stat Assoc 94:496–509CrossRef
14.
go back to reference Fleming ST, Rastogi A, Dmitrienko A, Johnson KD (1999) A comprehensive prognostic index to predict survival based on multiple comorbidities: a focus on breast cancer. Med Care 37(601–614):18 Fleming ST, Rastogi A, Dmitrienko A, Johnson KD (1999) A comprehensive prognostic index to predict survival based on multiple comorbidities: a focus on breast cancer. Med Care 37(601–614):18
16.
go back to reference Hou G, Zhang S, Zhang X, Wang P, Hao X, Zhang J (2013) Clinical pathological characteristics and prognostic analysis of 1,013 breast cancer patients with diabetes. Breast Cancer Res Tr 137:807–816. doi:10.1007/s10549-012-2404-y CrossRef Hou G, Zhang S, Zhang X, Wang P, Hao X, Zhang J (2013) Clinical pathological characteristics and prognostic analysis of 1,013 breast cancer patients with diabetes. Breast Cancer Res Tr 137:807–816. doi:10.​1007/​s10549-012-2404-y CrossRef
17.
go back to reference Jackson JM, Defor TA, Crain AL, Kerby T, Strayer L, Lewis CE, Whitlock E, Williams S, Bonds DE, Vitolins MZ, Rodabough RJ, Margolis KL (2013) Self-reported diabetes is a valid outcome in pragmatic clinical trials and observational studies. J Clin Epidemiol 66:349–350. doi:10.1016/j.jclinepi.2012.01.013 PubMedCrossRef Jackson JM, Defor TA, Crain AL, Kerby T, Strayer L, Lewis CE, Whitlock E, Williams S, Bonds DE, Vitolins MZ, Rodabough RJ, Margolis KL (2013) Self-reported diabetes is a valid outcome in pragmatic clinical trials and observational studies. J Clin Epidemiol 66:349–350. doi:10.​1016/​j.​jclinepi.​2012.​01.​013 PubMedCrossRef
18.
go back to reference Kaplan MA, Pekkolay Z, Kucukoner M, Inal A, Urakci Z, Ertugrul H, Akdogan R, Firat U, Yildiz I, Isikdogan A (2012) Type 2 diabetes mellitus and prognosis in early stage breast cancer women. Med Oncol 29:1576–1580. doi:10.1007/s12032-011-0109-4 PubMedCrossRef Kaplan MA, Pekkolay Z, Kucukoner M, Inal A, Urakci Z, Ertugrul H, Akdogan R, Firat U, Yildiz I, Isikdogan A (2012) Type 2 diabetes mellitus and prognosis in early stage breast cancer women. Med Oncol 29:1576–1580. doi:10.​1007/​s12032-011-0109-4 PubMedCrossRef
21.
go back to reference Liao S, Li J, Wei W, Wang L, Zhang Y, Li J, Wang C, Sun S (2011) Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pacific J Cancer Prevention 12:1061–1065 Liao S, Li J, Wei W, Wang L, Zhang Y, Li J, Wang C, Sun S (2011) Association between diabetes mellitus and breast cancer risk: a meta-analysis of the literature. Asian Pacific J Cancer Prevention 12:1061–1065
23.
go back to reference Lipscombe LL, Hux JE, Booth GL (2005) Reduced screening mammography among women with diabetes. Arch Intern Med 165:2090–2095PubMedCrossRef Lipscombe LL, Hux JE, Booth GL (2005) Reduced screening mammography among women with diabetes. Arch Intern Med 165:2090–2095PubMedCrossRef
24.
26.
go back to reference Margolis KL, Lihong Q, Brzyski R, Bonds DE, Howard BV, Kempainen S, Simin L, Robinson JG, Safford MM, Tinker LT, Phillips LS (2008) Validity of diabetes self-reports in the Women’s Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials 5:240–247. doi:10.1177/1740774508091749 PubMedCrossRefPubMedCentral Margolis KL, Lihong Q, Brzyski R, Bonds DE, Howard BV, Kempainen S, Simin L, Robinson JG, Safford MM, Tinker LT, Phillips LS (2008) Validity of diabetes self-reports in the Women’s Health Initiative: comparison with medication inventories and fasting glucose measurements. Clin Trials 5:240–247. doi:10.​1177/​1740774508091749​ PubMedCrossRefPubMedCentral
30.
go back to reference Peeters PJ, Bazelier MT, Vestergaard P, Leufkens HG, Schmidt MK, de Vries F, De Bruin ML (2013) Use of metformin and survival of diabetic women with breast cancer. Current drug safety 8:357–363PubMedCrossRef Peeters PJ, Bazelier MT, Vestergaard P, Leufkens HG, Schmidt MK, de Vries F, De Bruin ML (2013) Use of metformin and survival of diabetic women with breast cancer. Current drug safety 8:357–363PubMedCrossRef
33.
34.
go back to reference Schrauder MG, Fasching PA, Haberle L, Lux MP, Rauh C, Hein A, Bayer CM, Heusinger K, Hartmann A, Strehl JD, Wachter DL, Schulz-Wendtland R, Adamietz B, Beckmann MW, Loehberg CR (2010) Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol. doi:10.1007/s00432-010-0960-2 PubMed Schrauder MG, Fasching PA, Haberle L, Lux MP, Rauh C, Hein A, Bayer CM, Heusinger K, Hartmann A, Strehl JD, Wachter DL, Schulz-Wendtland R, Adamietz B, Beckmann MW, Loehberg CR (2010) Diabetes and prognosis in a breast cancer cohort. J Cancer Res Clin Oncol. doi:10.​1007/​s00432-010-0960-2 PubMed
35.
go back to reference Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20:1215–1221PubMedCrossRef Seidman A, Hudis C, Pierri MK, Shak S, Paton V, Ashby M, Murphy M, Stewart SJ, Keefe D (2002) Cardiac dysfunction in the trastuzumab clinical trials experience. J Clin Oncol 20:1215–1221PubMedCrossRef
36.
go back to reference Serrano C, Cortes J, De Mattos-Arruda L, Bellet M, Gomez P, Saura C, Perez J, Vidal M, Munoz-Couselo E, Carreras MJ, Sanchez-Olle G, Tabernero J, Baselga J, Di Cosimo S (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902. doi:10.1093/annonc/mdr348 PubMedCrossRef Serrano C, Cortes J, De Mattos-Arruda L, Bellet M, Gomez P, Saura C, Perez J, Vidal M, Munoz-Couselo E, Carreras MJ, Sanchez-Olle G, Tabernero J, Baselga J, Di Cosimo S (2012) Trastuzumab-related cardiotoxicity in the elderly: a role for cardiovascular risk factors. Ann Oncol 23:897–902. doi:10.​1093/​annonc/​mdr348 PubMedCrossRef
40.
go back to reference Xiao Y, Zhang S, Hou G, Zhang X, Hao X, Zhang J (2013) Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer. Tumour Biol. doi:10.1007/s13277-013-1270-5 Xiao Y, Zhang S, Hou G, Zhang X, Hao X, Zhang J (2013) Clinical pathological characteristics and prognostic analysis of diabetic women with luminal subtype breast cancer. Tumour Biol. doi:10.​1007/​s13277-013-1270-5
Metadata
Title
Diabetes, diabetes treatment and breast cancer prognosis
Authors
Juhua Luo
Beth Virnig
Michael Hendryx
Sijin Wen
Rowan Chelebowski
Chu Chen
Tomas Rohan
Lesley Tinker
Jean Wactawski-Wende
Lawrence Lessin
Karen Margolis
Publication date
01-11-2014
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 1/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-014-3146-9

Other articles of this Issue 1/2014

Breast Cancer Research and Treatment 1/2014 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