Risk of breast cancer by individual insulin use - an international multicenter study

  1. for the ISICA Group
  1. LG-B (LA-SER and National Conservatory of Arts and Crafts, both in Paris, France; Lamiae.Grimaldi{at}, DC (Edinburgh Cancer Research Centre, The University of Edinburgh, Edinburgh, United Kingdom; D.Cameron{at}, MM (Center for Therapeutic Innovation in Oncology and Hematology, Paris, France; me.marty{at}, AHB (Diabetes Centre, Heart of England NHS Foundation Trust, and University of Birmingham, both in Birmingham, United Kingdom; anthony.barnett{at}, FP-L (Department of Pathology, Center Jean-Perrin, University of Auvergne, Clermont-Ferrand, France; Frederique.PENAULT-LLORCA{at}, MP (Departments of Oncology and Medicine, McGill University, Gerald Bronfman Center, Montreal, Canada; michael.pollak{at}, BC (Endocrinology Department, University of Nantes, Nantes, France; Bernard.Charbonnel{at}, MRi (Oregon Health & Science University, Portland, Oregon, United States; riddlem{at}, LM (Department of Medical Oncology, Curie Institute, Paris, France; laurent.mignot{at}, J-FB (Epidemiology and biostatistics department, McGill University, and Clinical Epidemiology, H411, Lady Davis Institute, Général Juif Hospital, both in Montréal, Canada; jean-f.boivin{at}, AK (LA-SER Europe Limited, London, United Kingdom; Artak.Khachatryan{at}, MRo (LA-SER Center for Risk Research and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, both in Montreal, Canada; Michel.ROSSIGNOL{at}, JB (Department of Biostatistics, University Hospital of Rouen, Rouen, and INSERM U657, Bordeaux, France; jacques.benichou{at}, AA (INSERM, U708-Neuroepidemiology, and University Bordeaux-Segalen, both in Bordeaux, France; annick.alperovitch{at}, LA (LA-SER Europe Limited, and Department of Epidemiology, London School of Hygiene & Tropical Medicine, both in London, United Kingdom; Lucien.Abenhaim{at}
  1. Corresponding author: Lamiae Grimaldi Bensouda; Email: Lamiae.Grimaldi{at}


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 775 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 controls (n=3050; recruited from 580 general practices) by country, age, recruitment date, 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 anti-diabetic 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 to 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 vs. 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.

  • Received March 22, 2013.
  • Accepted August 9, 2013.

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