Small Increase in Diabetes Risk Seen in Older Breast Cancer Patients Taking Tamoxifen

In a Canadian study of more than 14,000 breast cancer survivors over 65 years of age, current use of tamoxifen appears to be associated with a small increased risk of diabetes. The findings do not mean tamoxifen is a direct cause of diabetes in this patient population, the study authors emphasized, but they said its use may increase diabetes risk in older women who already have known risk factors for diabetes, such as obesity or a family history of the disease.

The findings were published online on September 20, in the journal Cancer. Lead investigator Lorraine L. Lipscombe, MD, MSc, of Women’s College Hospital and the University of Toronto, and her coauthors noted that, while evidence of a link between breast cancer and diabetes is increasing, the association between cancer therapy and diabetes risk has been relatively unexplored. This possible association is important because many women with estrogen receptor–positive breast cancer are on tamoxifen therapy for about 5 years, and tamoxifen is sometimes used to reduce the risk of invasive breast cancer in high-risk women aged 35 and older.

For their nested case-control study, Dr. Lipscombe and coinvestigators used population-based health databases in Ontario, Canada to identify women over 65 years of age who had early stage breast cancer between April 1, 1996 and March 31, 2006. There were 14,360 breast cancer survivors identified (mean age, 74.9 years). During a follow-up visit, on March 31, 2008, each of the breast cancer patients diagnosed with diabetes was age-matched with as many as 5 controls who did not develop diabetes.

After adjusting for other diabetes risk factors, Dr. Lipscombe and coauthors compared the likelihood of diabetes between current tamoxifen users vs tamoxifen nonusers, based on prescriptions the women were taking at the time they were diagnosed with diabetes. They also compared diabetes risk in current aromatase inhibitor users vs nonusers.

A total of 1,445 (10% of the study population) developed diabetes over a mean follow-up of 5.2 years. Current tamoxifen therapy was associated with about a 25% higher risk of diabetes compared with no tamoxifen therapy (adjusted odds ratio, 1.24; 95% CI, 1.08-1.42; P = .002). There was no association between aromatase inhibitor therapy and diabetes.

In conclusion, the authors wrote that their findings of an association between tamoxifen therapy and an increased incidence of diabetes in older breast cancer survivors  “suggest that tamoxifen treatment may exacerbate an underlying risk of diabetes in susceptible women.” Tamoxifen may increase diabetes incidence through its inhibition of estrogen, which is believed to play a role in the control of blood sugar levels. Further studies are needed, Dr. Lipscombe said, of possible associations with increased diabetes risk in younger breast cancer patients and in women taking aromatase inhibitors for breast cancer.