Prolonged use of human insulin increases breast cancer risk in Taiwanese women with type 2 diabetes
Journal
BMC Cancer
Journal Volume
15
Journal Issue
1
Pages
846
Date Issued
2015
Author(s)
Abstract
Background: 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. Methods: The 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. Results: There 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 ?67months for time since starting insulin, ?39,000 units for cumulative dose of insulin, and ?21.8months 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. Conclusions: This 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. ? 2015 Tseng.
SDGs
Other Subjects
angiotensin receptor antagonist; dipeptidyl carboxypeptidase inhibitor; human insulin; hydroxymethylglutaryl coenzyme A reductase inhibitor; metformin; antidiabetic agent; isophane insulin; adult; Article; breast cancer; cancer incidence; cancer risk; controlled study; disease association; drug exposure; drug use; female; human; major clinical study; middle aged; non insulin dependent diabetes mellitus; risk assessment; Taiwanese; treatment duration; Breast Neoplasms; chemically induced; clinical trial; Diabetes Mellitus, Type 2; drug administration; incidence; multicenter study; retrospective study; risk assessment; risk factor; Taiwan; Breast Neoplasms; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Incidence; Isophane Insulin, Human; Middle Aged; Retrospective Studies; Risk Assessment; Risk Factors; Taiwan
Publisher
BioMed Central Ltd.
Type
journal article