SAN DIEGO—Current or recent tamoxifen therapy was associated with an increased risk of developing type 2 diabetes in women older than 65 years who survived invasive breast cancer. No association was found between aromatase inhibitors (AIs) and development of type 2 diabetes, but the numbers of women on AIs was small. These findings of a population-based, case-control study in Toronto, Ontario, Canada, were presented at the 71st Scientific Sessions of the American Diabetes Association.
“To our knowledge, this is the first study to examine the association between tamoxifen and risk of type 2 diabetes. We found a modest odds ratio for the association, and this suggests that tamoxifen may exacerbate an underlying risk of diabetes in susceptible women. Further studies are needed to explore this association,” said Lorraine L. Lipscombe, MD, Women’s College Research Institute, University of Toronto, Canada.
Lipscombe explained that type 2 diabetes is increased in women with breast cancer and it portends a worse prognosis. “The reverse also may be true; that is, that breast cancer patients may be at increased risk of diabetes,” she noted. “For some time, the association be - tween estrogen and diabetes has been known. Tamoxifen is an estrogen receptor antagonist, and case reports suggest an increased risk of factors associated with diabetes in patients on tamoxifen, such as hypertriglyceridemia, steatohepatitis, and visceral fat.”
The study was based on a cohort of 14,360 women with invasive breast cancer diagnosed between 1996 and 2008 identified in the large Ontario Cancer Registry and physicians’ claims and hospital abstracts. Exclusions were metastasis, known diabetes, previous cancer, surgery, and expected survival of less than 1 year. In total, 1445 cases of incident diabetes diagnosed during that period were matched with up to 5 controls, who did not have diabetes, for age and date of breast cancer diagnosis (n = 7220).
Of the cases of type 2 diabetes identified, 531 (37%) were prescribed tamoxifen, and 127 (9%) were prescribed an AI. Tamoxifen use was defined as filling at least 2 prescriptions. Cases and controls were stratified according to current/ recent (within 6 months) tamoxifen users and previous users (stopped 6 months ago or more).
Current/recent tamoxifen use was associated with a significant increase in risk of type 2 diabetes (adjusted odds ratio, 1.24 [95% confidence interval, 1.08-1.41]; P = .0027). The risk began to increase at years 2 and 3 of tamoxifen use. Previous tamoxifen use and AI use were not associated with an increased risk of diabetes.
Lipscombe cited several limitations of the study, including incomplete cancer data, and no data on risk factors such as body mass index, metabolic factors, family history, or ethnicity. “We cannot exclude bias from this observational study, but this is the first report of this association and it is hypothesis-generating,” she told listeners
