Insulin-like growth factor 1 and musculoskeletal pain among breast cancer patients on aromatase inhibitor therapy and women without a history of cancer

Abstract

Musculoskeletal pain is a common side effect of aromatase inhibitors (AIs), the adjuvant hormonal treatment of choice for postmenopausal estrogen-receptor-positive breast cancer. Although the pain is usually attributed to the estrogen depletion associated with AIs, not all women on AIs experience these symptoms. Thus, the goal of this study was to examine whether changes in the insulin-like growth factor (IGF) axis were associated with pain among women initiating AI therapy or a comparison group of women without a history of cancer. Data were analyzed from a cohort study of 52 breast cancer patients for whom AI therapy was planned and 88 women without a history of cancer. Questionnaire data on pain symptoms were collected, and blood was drawn at baseline (prior to AI therapy for patients) and 6 months after baseline. The blood samples were assayed for IGF-1 and IGF-binding protein-3 (IGFBP-3). While results showed no statistically significant changes in any of the measures across time for either the breast cancer or the comparison group, increases in both IGF-1 concentrations and the IGF-1/IGFBP-3 ratio over the first 6 months of AI treatment were significantly associated with the onset or increase in musculoskeletal pain among the breast cancer patients. Associations between IGF-1, IGFBP-3, and the IGF-1/IGFBP-3 ratio and pain were not observed in the comparison group. Although preliminary, findings from this study implicate the IGF axis in the development of AI-associated musculoskeletal pain and represent a first step in developing effective interventions to alleviate this side effect.