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At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
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Cancer Causes & Control
Published in: Cancer Causes & Control 8/2015

01-08-2015 | Original paper

Associations between diabetes medication use and risk of second breast cancer events and mortality

Authors: Gregory S. Calip, Onchee Yu, Kent F. Hoskins, Denise M. Boudreau

Published in: Cancer Causes & Control | Issue 8/2015

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Abstract

Purpose

Diabetes and certain diabetes medications have been shown to influence breast cancer (BC) risk. Less is known about their relation to BC outcomes. Our objective was to evaluate the effects of diabetes and diabetes medications on risk of second breast cancer events (SBCE) and mortality.

Methods

This population-based cohort study was conducted among women diagnosed with early-stage (I–II) BC and enrolled in an integrated health plan. Exposures of interest were diabetes and medication classes including insulin, metformin, and sulfonylureas. Outcomes of interest were SBCE defined as recurrence or second primary BC, BC-specific mortality, and all-cause mortality. We used multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for diabetes and medication use while accounting for potential confounders and competing risks.

Results

Among 4,216 women, 13 % developed SBCE during a median follow-up of 6.3 years. 610 women had diabetes of which 76 % used oral diabetes medication and/or insulin. Findings suggested that diabetes increased the risk of recurrence (HR = 1.57; 95 % CI 1.09–2.25) but not overall SBCE (HR = 1.29; 95 % CI 0.94–1.76) or second primary BC (HR = 0.74; 95 % CI 0.39–1.41). Among women with diabetes, insulin use was associated with increased risks of recurrence (HR = 1.94; 95 % CI 1.08–3.48) and all-cause mortality (HR = 2.33; 95 % CI 1.70–3.20). Metformin use was associated with lower all-cause mortality (HR = 0.55; 95 % CI 0.38–0.79).

Conclusions

Our findings show an association between diabetes and increased recurrence risk, and risk may be greater among insulin users. Metformin may reduce all-cause mortality among BC survivors. Given the growing breast cancer survivor population, further research in larger, more diverse populations is warranted.
Appendix
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Literature
1.
American Cancer Society (2013) Breast cancer facts and figures 2013–2014. American Cancer Society Inc, Atlanta
2.
3.
Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D (2010) Diabetes and cancer: a consensus report. Diab Care 33(7):1674–1685. doi:10.​2337/​dc10-0666 CrossRef
4.
5.
6.
7.
8.
9.
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(23):2844–2852. doi:10.​1200/​JCO.​2011.​39.​7505 PubMedCentralPubMedCrossRef
10.
Ruiter R, Visser LE, van Herk-Sukel MP, Coebergh JW, Haak HR, Geelhoed-Duijvestijn PH, Straus SM, Herings RM, Stricker BH (2012) Risk of cancer in patients on insulin glargine and other insulin analogues in comparison with those on human insulin: results from a large population-based follow-up study. Diabetologia 55(1):51–62. doi:10.​1007/​s00125-011-2312-4 PubMedCentralPubMedCrossRef
11.
Lind M, Fahlen M, Eliasson B, Oden A (2012) The relationship between the exposure time of insulin glargine and risk of breast and prostate cancer: an observational study of the time-dependent effects of antidiabetic treatments in patients with diabetes. Prim Care Diab 6(1):53–59. doi:10.​1016/​j.​pcd.​2011.​10.​004 CrossRef
12.
13.
14.
Morden NE, Liu SK, Smith J, Mackenzie TA, Skinner J, Korc M (2011) Further exploration of the relationship between insulin glargine and incident cancer: a retrospective cohort study of older Medicare patients. Diab Care 34(9):1965–1971. doi:10.​2337/​dc11-0699 CrossRef
15.
16.
17.
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN, Gonzalez-Angulo AM (2009) Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol 27(20):3297–3302. doi:10.​1200/​JCO.​2009.​19.​6410 PubMedCentralPubMedCrossRef
18.
Bonanni B, Puntoni M, Cazzaniga M, Pruneri G, Serrano D, Guerrieri-Gonzaga A, Gennari A, Trabacca MS, Galimberti V, Veronesi P, Johansson H, Aristarco V, Bassi F, Luini A, Lazzeroni M, Varricchio C, Viale G, Bruzzi P, Decensi A (2012) Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial. J Clin Oncol 30(21):2593–2600. doi:10.​1200/​JCO.​2011.​39.​3769 PubMedCrossRef
19.
Blin P, Lassalle R, Dureau-Pournin C, Ambrosino B, Bernard MA, Abouelfath A, Gin H, Le Jeunne C, Pariente A, Droz C, Moore N (2012) Insulin glargine and risk of cancer: a cohort study in the French National Healthcare Insurance Database. Diabetologia 55(3):644–653. doi:10.​1007/​s00125-011-2429-5 PubMedCentralPubMedCrossRef
20.
Kurtzhals P, Schaffer L, Sorensen A, Kristensen C, Jonassen I, Schmid C, Trub T (2000) Correlations of receptor binding and metabolic and mitogenic potencies of insulin analogs designed for clinical use. Diabetes 49(6):999–1005PubMedCrossRef
21.
22.
Mayer D, Chantelau E (2010) Treatment with insulin glargine (Lantus) increases the proliferative potency of the serum of patients with type-1 diabetes: a pilot study on MCF-7 breast cancer cells. Arch Physiol Biochem 116(2):73–78. doi:10.​3109/​1381345100363143​9 PubMedCrossRef
23.
24.
25.
26.
Saunders KW, Davis RL, Stergachis A (2005) Group health cooperative. In: Strom BL (ed) Pharmacoepidemiology, 4th edn. Wiley, Chichester, pp 223–239
27.
Boudreau DM, Doescher MP, Jackson JE, Fishman PA, Saver BG (2004) Impact of healthcare delivery system on where HMO-enrolled seniors purchase medications. Ann Pharmacother 38(7–8):1317–1318. doi:10.​1345/​aph.​1D569 PubMedCrossRef
28.
29.
Singletary SE, Allred C, Ashley P, Bassett LW, Berry D, Bland KI, Borgen PI, Clark GM, Edge SB, Hayes DF, Hughes LL, Hutter RV, Morrow M, Page DL, Recht A, Theriault RL, Thor A, Weaver DL, Wieand HS, Greene FL (2003) Staging system for breast cancer: revisions for the 6th edition of the AJCC Cancer Staging Manual. Surg Clin North Am 83(4):803–819. doi:10.​1016/​S0039-6109(03)00034-3 PubMedCrossRef
30.
31.
32.
Hebert PL, Geiss LS, Tierney EF, Engelgau MM, Yawn BP, McBean AM (1999) Identifying persons with diabetes using Medicare claims data. Am J Med Qual 14(6):270–277PubMedCrossRef
33.
Newton KM, LaCroix AZ, Heckbert SR, Abraham L, McCulloch D, Barlow W (2003) Estrogen therapy and risk of cardiovascular events among women with type 2 diabetes. Diab Care 26(10):2810–2816CrossRef
34.
Newton KM, Wagner EH, Ramsey SD, McCulloch D, Evans R, Sandhu N, Davis C (1999) The use of automated data to identify complications and comorbidities of diabetes: a validation study. J Clin Epidemiol 52(3):199–207PubMedCrossRef
35.
Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B, American Diabetes Association, European Association for Study of Diabetes (2009) Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diab Care 32(1):193–203. doi:10.​2337/​dc08-9025 CrossRef
36.
Hudis CA, Barlow WE, Costantino JP, Gray RJ, Pritchard KI, Chapman JA, Sparano JA, Hunsberger S, Enos RA, Gelber RD, Zujewski JA (2007) Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 25(15):2127–2132. doi:10.​1200/​JCO.​2006.​10.​3523 PubMedCrossRef
37.
38.
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(5):1202–1211. doi:10.​1002/​cncr.​26439 PubMedCentralPubMedCrossRef
39.
Lega IC, Austin PC, Gruneir A, Goodwin PJ, Rochon PA, Lipscombe LL (2013) Association between metformin therapy and mortality after breast cancer: a population-based study. Diab Care 36(10):3018–3026. doi:10.​2337/​dc12-2535 CrossRef
40.
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. Curr Drug Saf 8(5):357–363PubMedCrossRef
41.
42.
Deyo RA, Cherkin DC, Ciol MA (1992) Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 45(6):613–619PubMedCrossRef
43.
Calip GS, Hubbard RA, Stergachis A, Malone KE, Gralow JR, Boudreau DM (2015) Adherence to oral diabetes medications and glycemic control during and following breast cancer treatment. Pharmacoepidemiol Drug Saf 24(1):75–85. doi:10.​1002/​pds.​3660 PubMedCrossRef
44.
45.
Sabatino SA, Thompson TD, Wu XC, Fleming ST, Kimmick GG, Trentham-Dietz A, Cress R, Anderson RT (2014) The influence of diabetes severity on receipt of guideline-concordant treatment for breast cancer. Breast Cancer Res Treat 146(1):199–209. doi:10.​1007/​s10549-014-2998-3 PubMedCrossRef
46.
Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, Rosner B, Speizer FE, Pollak M (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351(9113):1393–1396. doi:10.​1016/​S0140-6736(97)10384-1 PubMedCrossRef
47.
Goodwin PJ ClinicalTrials.gov—A phase III randomized trial of metformin versus placebo on recurrence and survival in early stage breast cancer NCT01101438, Accessed 18 Feb 2014
Metadata
Title
Associations between diabetes medication use and risk of second breast cancer events and mortality
Authors
Gregory S. Calip
Onchee Yu
Kent F. Hoskins
Denise M. Boudreau
Publication date
01-08-2015
Publisher
Springer International Publishing
Published in
Cancer Causes & Control / Issue 8/2015
Print ISSN: 0957-5243
Electronic ISSN: 1573-7225
DOI
https://doi.org/10.1007/s10552-015-0599-z

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