Prolonged use of human insulin increases breast cancer risk in Taiwanese women with type 2 diabetes.

Chin-Hsiao Tseng

doi:10.1186/s12885-015-1876-7

Abstract

BackgroundHuman insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes.MethodsThe reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,033 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the adjusted hazard ratios were estimated by Cox regression. The potential risk modification by concomitant treatment with metformin, statin and angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) was also evaluated.ResultsThere were 59,798 ever-users and 422,235 never-users of human insulin, with respective numbers of incident breast cancer of 559 (0.93 %) and 4,711 (1.12 %), and respective incidence of 207.9 and 215.1 per 100,000 person-years. The overall adjusted hazard ratio (95 % confidence interval) did not show a significant association with insulin [1.033 (0.936-1.139)]. However, patients in the third tertiles of dose–response parameters might show a significantly higher risk of breast cancer while compared to never-users: 1.185 (1.026-1.368), 1.260 (1.096-1.450) and 1.257 (1.094-1.446) for ≥67 months for time since starting insulin, ≥39,000 units for cumulative dose of insulin, and ≥21.8 months for cumulative duration of insulin, respectively. Additional analyses suggested that the breast cancer risk associated with human insulin use might be beneficially modified by concomitant use of metformin, statin and ACEI/ARB.ConclusionsThis study discloses a significantly higher risk of breast cancer associated with prolonged use of human insulin. The increased risk of breast cancer associated with human insulin use may be modified by medications such as metformin, statin and ACEI/ARB.

Highlights

Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate
Insulin can be found in human breast cancer tissues [3], and some breast cancers are responsive to insulin and administration of insulin/insulin-like growth factor 1 (IGF-1) receptor family kinase inhibitor or alloxan to produce a status of hypoinsulinemia by destroying the insulin producing pancreatic β-cells may inhibit tumor growth of breast cancer cell line [4]
The purpose of the present study was to evaluate whether human insulin use without confounding exposure to insulin analogs would increase the risk of breast cancer in female patients with type 2 diabetes mellitus, by using the National Health Insurance (NHI) databases of Taiwan

Summary

Introduction

Human insulin is commonly used to treat hyperglycemia in patients with diabetes, but its potential link with female breast cancer is under debate. This study investigated whether human insulin use might be associated with breast cancer risk in Taiwanese women with type 2 diabetes. Diabetes mellitus may increase the risk of breast cancer in terms of incidence and mortality [1, 2]. Whether insulin use can be responsible for the increased risk of diabetes-related breast cancer is still under debate. Some in vitro and observational studies provide evidence for a potential link between insulin and breast cancer. Mammalian target of rapamycin (mTOR) is activated by insulin and insulin-mediated breast cancer progression in patients with type 2 diabetes mellitus may be abrogated by inhibition of mTOR [5]. The Women’s Health Initiative study prospectively showed that elevated insulin level may predict postmenopausal breast cancer [6]

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