Insulin and IGF-1 in breast cancer patients are associated with tumor cell proliferation (Ki67) in their breast tumors

Abstract

Introduction: Excess weight, insulin, insulin resistance and IGF-1 have been associated with breast cancer prognosis, but less is known about the association between these factors and Ki67 index, a marker of cell proliferation in malignant breast tumors. Methods: Women with newly diagnosed stage III invasive breast cancer, aged 35-75 years, were invited to participate in a small clinical study, in order to study whether insulin, IGF-1 and insulin resistance [Homeostasis Model Assessment (HOMA)-score], were associated with Ki-67 index, a marker of cell proliferation in malignant breast tumors. Before surgery, body mass index [BMI, kg/m], waist circumference [cm], and total and truncal fat percentage [dual-emission X-ray absorptiometry], and fasting serum concentrations of insulin, IGF-1 and insulin resistance were assessed and determined. Ki67 index was determined as the percentage of Ki67-positive tumor cells according to national and international guidelines. Linear regression models were used to test for associations between Ki67 and selected patient characteristics. Results: Among these 45 breast cancer patients included, mean age at diagnosis was 54.9 years, BMI was 24.8 kg/m and mean waist circumference was 87.0 cm. Altogether, 91.1% of patients had estrogen receptor (ER)-positive tumors (> 1 % ER+), and 28.9% had axillary lymph node metastases. There was a negative association between Ki67 index and age (p=0.012), ER-positive tumors (p<0.0001), and progesterone receptor (PR)-positive tumors (p=0.001), and a positive association between Ki67 and histologic grade 3 versus 1 (p <0.0001). Among premenopausal patients, Ki67 was positively associated with insulin resistance, (p=0.097) and IGF-1 (p=0.025). Conclusion: Our results, although small number of patients included, hypothesize an association between IGF-1, insulin resistance and Ki67 index. Our results should be focused in larger studies in where more detailed subgroup analysis can be performed.