Breast cancer and type 2 diabetes are both growing in incidence in developed countries. Both these diseases are associated with overweight and obesity, and there is growing evidence for a link between them. People who are overweight and obese but do not have diabetes often suffer from the pre-diabetic conditions hyperinsulinemia, in which the concentration of circulating insulin is increased, and insulin resistance, in which insulin becomes less effective; levels of the metabolic hormone adiponectin are also decreased in obese compared to lean individuals. Obesity-related metabolic changes like these have been associated with an increased risk of developing breast cancer and with poor outcomes in this disease, but the mechanism through which this link arises is unknown.

A group of US-based researchers led by Catherine Duggan at the Fred Hutchinson Cancer Research Center in Seattle, WA, has evaluated the link between metabolic characteristics associated with high body weight and mortality in patients with breast cancer¹. A cohort of 527 women diagnosed with local or regional breast cancer was selected from those enrolled in the HEAL study² of eating patterns, activity and lifestyle in breast cancer patients, approximately three years after first diagnosis. Reasons for exclusion included recent treatment for recurrent breast cancer and diagnosed type 2 diabetes. Participants completed detailed questionnaires, had their BMI determined and gave blood samples that were tested for glucose, insulin and adiponectin levels. Individuals were followed up until death from any cause or until the end of the study in December 2006; the median follow-up time was about 80 months.

Sixty-two deaths occurred in the study cohort during the follow-up period, of which twenty-eight were due to breast cancer. Hazard ratios for all-cause mortality and breast cancer mortality were calculated for glucose, insulin and adiponectin levels and for the Homeostatic Model Assessment (HOMA) score, which is calculated from fasting insulin and glucose levels and which measures insulin resistance. High HOMA scores (indicating a high degree of insulin resistance) were found to correlate inversely with adiponectin levels. Elevated HOMA scores were also significantly associated with higher risk of both breast cancer mortality and overall mortality. This association remained after adjusting for age, race, tamoxifen use and even for BMI. Adiponectin levels above the median were associated with lower breast cancer mortality, although there was no statistically significant association between mortality and adiponectin levels if these were measured continuously.

These results indicates that there is a clear link between increased mortality and forms of metabolic dysfunction that are also associated with obesity and with increased risk of type 2 diabetes. Although this association is not completely new, this study is the first to link lower adiponectin levels with raised breast cancer mortality. Writing in an editorial in the Journal of Clinical Oncology accompanying this and three further papers that link breast cancer and insulin resistance, Andrea DeCensi and Alessandra Gennari from Galliera Hospital, Genoa, Italy, call for an integrated approach to a treatment of the two often co-morbid conditions.

Reference

1. Duggan, C., Irwin, M.L., Xiao, L., Henderson, K.D., Smith, A.W., Baumgartner, R.N., Baumgartner, K.B., Bernstein, L., Ballard-Barbash, R. and McTiernan, A. (2010) Associations of Insulin Resistance and Adiponectin With Mortality in Women With Breast Cancer J. Clinical Oncology, published online ahead of print 29 November 2010. doi: 10.1200/JCO.2009.26.4473

2. McTiernan A, Rajan KB, Tworoger SS, Irwin M, Bernstein L, Baumgartner R, Gilliland F, Stanczyk FZ, Yasui Y, Ballard-Barbash R (2003) Adiposity and sex hormones in postmenopausal breast cancer survivors J Clin Oncol 21: 1961-6.