SAN ANTONIO – Diabetes is independently associated with a 27% increased risk of breast cancer, but this elevated risk is confined to postmenopausal type 2 diabetic patients, a large meta-analysis has shown.
The meta-analysis, which included 40 published studies and 56,111 women with breast cancer, found no association between risk of the malignancy and circulating serum insulin level, insulin growth factor–1 level, fasting blood glucose level, or C-peptide concentration.
These findings suggest that the hyperinsulinemic theory of the pathogenesis of breast cancer may need to be reevaluated in order to account for the increased risk being confined to postmenopausal patients and unrelated to indices of metabolic control, Dr. Peter Boyle said at the annual San Antonio Breast Cancer Symposium.
The key risk factors for breast cancer that emerged from the meta-analysis were adiposity and lack of physical activity. Both are also well established as risk factors for diabetes.
Based on the findings from this meta-analysis, efforts to avoid overweight and increase physical activity should form the basis of a common public health strategy simultaneously aimed at preventing diabetes and breast cancer, according to Dr. Boyle of the International Prevention Research Institute in Lyon, France.
High levels of physical activity, whether occupational or recreational, were independently associated with a 17% reduction in the relative risk of being diagnosed with breast cancer in premenopausal women and a 12% decrease in the postmenopausal population.
The relationship between adiposity and breast cancer was less straightforward. Premenopausal women who were overweight or obese had a significantly lower breast cancer risk than did leaner women, while breast cancer risk was increased in adipose postmenopausal women. More specifically, a 5-U increase in body mass index – equivalent to an extra 14.5 kg in a woman 1.7 m tall – was associated with an 11% increased risk of breast cancer in postmenopausal women but a 10% reduction in risk in premenopausal women.
Dr. Boyle and coworkers also presented a related meta-analysis looking at breast cancer risk in women using insulin glargine (Lantus). The study was prompted by recent evidence linking pioglitazone to a possible increase in bladder cancer, liraglutide and pancreatic cancer, insulin use and lung cancer, and exenatide and pancreatic cancer.
This meta-analysis included 18 epidemiologic studies published within the past 3 years. Collectively the studies involved 4,080 cases of breast cancer in 903,675 patients followed for 2.7 million person-years.
The meta-analysis demonstrated no increase in breast cancer risk in insulin glargine users, compared with users of other insulins. Indeed, the risk of all forms of cancer was 9% lower in insulin glargine users, a statistically significant reduction. This was driven by a 14% reduction in the relative risk of colorectal cancer.
Another reassuring finding was that breast cancer risk did not increase with longer use of insulin glargine, as would be expected if a causal relationship existed, he added.
Both meta-analyses were funded by Sanofi-Aventis, which markets glargine. Dr. Boyle reported having no relevant financial conflicts, although several of his coinvestigators have served on advisory boards for Sanofi-Aventis and other insulin manufacturers.