Higher Insulin Resistance and Adiposity in Postmenopausal Women With Breast Cancer Treated With Aromatase Inhibitors

CONTEXT: Aromatase deficiency causes obesity and insulin resistance in aromatase knockout mice and humans with rare mutations of the aromatase gene (CYP19). Aromatase inhibitors are a commonly prescribed therapy for postmenopausal breast cancer. OBJECTIVE: We hypothesized that aromatase inhibitors induce obesity and insulin resistance when used in treatment of breast cancer. DESIGN: Case-control study. SETTING: University teaching hospital. PARTICIPANTS: Patients with postmenopausal breast cancer (n = 20) treated with aromatase inhibitors and 20 age-matched control subjects. MAIN OUTCOME MEASURES: The primary outcome measure was insulin sensitivity index – Matsuda, derived from a 75-g oral glucose tolerance test. Body composition was assessed by dual energy x-ray absorptiometry and biopsy specimens of subcutaneous adipose tissue obtained for assessment of mRNA transcript levels. Data are reported as mean ± SEM (patients receiving inhibitors vs control group, respectively). RESULTS: Aromatase inhibitor therapy was associated with significantly lower insulin sensitivity (5.15 ± 0.45 vs 6.80 ± 0.64; P = 0.041), higher peak insulin concentration after oral glucose tolerance test (693.4 ± 78.6 vs 527.6 ± 85.5 pmol/L; P = 0.035), greater percentage of body fat (38.4% ± 1.0% vs 34.6% ± 1.3%; P = 0.026), and higher plasma leptin concentration (23.5 ± 2.8 vs 15.5 ± 2.3 ng/mL; P = 0.035). CONCLUSION: Women who received aromatase inhibitors for postmenopausal breast cancer had greater percentage body fat and insulin resistance compared with control subjects with no history of breast cancer.