Sweetening breast cancer risk

Experimental and epidemiological evidence have previously suggested that circulating glucose and insulin may play a role in the emergence of breast cancer. Now a statistical analysis of baseline plasma levels of these compounds shows that elevated serum levels may indeed be a risk factor in postmenopausal women.

Geoffrey Kabat, Mimi Kim, Marc Gunter, Gloria Ho, Howard Strickler, and Thomas Rohan of the Albert Einstein College of Medicine, New York, worked on the research with Bette Caan of the Kaiser Permanente of Northern California, Rowan Chlebowski of the Los Angeles Biomedical Research Institute. Beatriz Rodriguez of the University of Hawaii, James Shikany of the University of Alabama at Birmingham, and Mara Vitolins of Wake Forest University, North Carolina.

The team explain how experimental and epidemiological evidence have suggested a role for circulating glucose and insulin in the initiation of breast cancer. "However, few cohort studies have examined breast cancer risk in association with glucose and insulin levels, and studies to date have had only baseline measurements of exposure," they point out.

The risk of postmenopausal breast cancer has long been associated with obesity and diabetes, which are, of course, characterised by increased insulin resistance, and the consequent increases in circulating levels of insulin and glucose. Insulin has previously been shown to cause cell proliferation in animal models of breast tumour growth and in turn high glucose levels may exacerbate insulin resistance.

"It is plausible that relatively high levels of glucose and/or insulin may play a role in the etiology of breast cancer," the researchers hypothesised.

With that in mind, the team has now carried out a longitudinal study of postmenopausal breast cancer risk. A longitudinal study usually involves monitoring a group of individuals at regular intervals over a relatively long period of time. The team looked at the 6% random sample of women in the Women's Health Initiative clinical trials. They analysed their fasting blood sample data, which provided at baseline and at years 1, 3 and 6, glucose and insulin levels. They also included a 1% sample of women in the observational study, who had glucose and insulin measured in fasting blood samples drawn at baseline and in year 3.

With the data in hand, they turned to Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals to determine whether or not there was an association between baseline and follow-up measurements of serum glucose and insulin and breast cancer risk. The team explains that all their statistical analyses were two-sided; cutting out the extremes at either side of the Bell curve.

"Among 5,450 women with baseline serum glucose and insulin values, 190 incident cases of breast cancer were ascertained over a median of 8.0 years of follow-up," the team explains. The highest tertile of baseline insulin, relative to the lowest, was associated with a twofold increase in risk in the total population (multivariable hazard ratio 2.22, 95% confidence interval 1.39-3.53) and with a threefold increase in risk in women who were not enrolled in the intervention arm of any clinical trial (multivariable hazard ratio 3.15, 95% confidence interval 1.61-6.17)."

However, they found that glucose levels showed no association with risk and analysis of the repeated measurements supported the results of their baseline analysis. "Although the most recent glucose measurement and the average of all glucose measurements were associated with breast cancer risk in all participants," the team explains, "these associations decreased toward the null and were no longer signi?cant when insulin was included in the model."

The most significant conclusion, therefore, is that these data suggest that postmenopausal women who have elevated serum insulin levels may be at greater risk factor than others for breast cancer.