Risk of Breast Cancer by Individual Insulin Use: An International Multicenter Study

• Published in: Diabetes care Vol. 37; no. 1; pp. 134 - 143
• Main Authors: Grimaldi-Bensouda, Lamiae, Cameron, David, Marty, Michel, Barnett, Anthony H., Penault-Llorca, Frédérique, Pollak, Michael, Charbonnel, Bernard, Riddle, Matthew, Mignot, Laurent, Boivin, Jean-François, Khachatryan, Artak, Rossignol, Michel, Bénichou, Jacques, Alpérovitch, Annick, Abenhaim, Lucien
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.01.2014
• Subjects: Aged; Biological and medical sciences; Breast cancer; Breast Neoplasms - epidemiology; Canada; Cancer; Case-Control Studies; Diabetes; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 2 - drug therapy; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Female; France; Gynecology. Andrology. Obstetrics; Health aspects; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Insulin; Insulin Aspart - therapeutic use; Insulin Glargine; Insulin Lispro - therapeutic use; Insulin, Long-Acting - therapeutic use; Insulin, Regular, Human - therapeutic use; Insulins - adverse effects; Insulins - therapeutic use; Mammary gland diseases; Medical sciences; Metabolic diseases; Middle Aged; Oncology, Experimental; Pharmaceutical industry; Physicians (General practice); Regression analysis; Risk assessment; Risk Factors; Tumors; United Kingdom; World; Canada; United Kingdom; France; United States; United Kingdom > UK; Human; Pancreatic hormone; Breast disease; Nutrition; Multicenter study; Use; Metabolic diseases; Risk; Breast cancer; Malignant tumor; Insulin; Mammary gland diseases; Risk factor; Mammary gland; Endocrinology; Cancer; International
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc13-0695

OBJECTIVE Several studies have been published in 2009 suggesting a possible association between insulin glargine and increased risk of malignancies, including breast cancer. The objective of this study was to assess the relation between the individual insulins (glargine, aspart, lispro, and human insulin) and development of breast cancer. RESEARCH DESIGN AND METHODS Seven hundred seventy-five incident cases of primary invasive or in situ carcinoma breast cancer occurring in women with diabetes from 92 centers in the U.K., Canada, and France were matched to a mean of 3.9 diabetic community control subjects (n = 3,050; recruited from 580 general practices) by country, age, recruitment date, and diabetes type and management. The main risk model was a multivariate conditional logistic regression model with case/control status as the dependent variable and individual insulin use, 8 years preceding the index date, as the independent variable, controlling for past use of any insulin, oral antidiabetes drugs, reproductive factors, lifestyle, education, hormone replacement therapy and history of contraceptive use, BMI, comorbidities, diabetes duration, and annual number of physician visits. Glargine was also compared with every other insulin by computing all ratios using the variance-covariance matrix of logistic model parameters. RESULTS Adjusted odds ratios of breast cancer for each type of insulin versus no use of that insulin were 1.04 (95% CI 0.76-1.44) for glargine, 1.23 (0.79-1.92) for lispro, 0.95 (0.64-1.40) for aspart, and 0.81 (0.55-1.20) for human insulin. Two-by-two comparisons found no difference between glargine and the different types of insulins. Insulin dosage or duration of use and tumor stage did not change the results. CONCLUSIONS This international study found no difference in the risk of developing breast cancer in patients with diabetes among the different types of insulin with short- to mid-term duration of use. Longer-term studies would be of interest.