Arthralgia induced by endocrine treatment for breast cancer: A prospective study of serum levels of insulin like growth factor-I, its binding protein and oestrogens

Abstract

Background: Aromatase inhibitors (AIs) frequently induce or enhance musculoskeletal problems (AI-induced musculoskeletal syndrome (AIMSS)) which sometimes are debilitating. Apart from low oestrogen levels, underlying mechanisms are unknown and likely multiple. We previously hypothesised a role for the growth hormone/insulin like growth factor-I (IGF-I) axis. Here, we report the effect of tamoxifen and AI on IGF-I, IGF binding protein-3 (IGFBP-3) and oestrogen levels from a prospective study.

Materials and methods: Postmenopausal women with an early breast cancer scheduled to start adjuvant endocrine therapy with an AI or tamoxifen were recruited. A rheumatologic questionnaire was completed and serum was collected for assessment of IGF-I, IGFBP-3 and oestrogen levels. Re-evaluation was done after 3, 6 and 1 2months of therapy.

Results: 84 patients started on tamoxifen (n=42) or an AI (n=42). 66% of the latter group experienced worsening of pre-existing or de novo complaints in joint and/or muscle, compared to 29% of tamoxifen-treated patients. AI therapy resulted in elevated IGF-I levels with a statistically significant increase at 6months (p=0.0088), whereas tamoxifen users were characterised by a decrease in IGF-I levels at all follow-up times (p<0.0004). No effect on IGFBP-3 was seen in the latter group. AI-users, however, showed decreased IGFBP-3 levels at 12 months (p=0.0467). AIMSS was characterised by a decrease in IGFBP-3 levels (p=0.0007) and a trend towards increased IGF-I/IGFBP-3 ratio (p=0.0710).

Conclusion: These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis.

Keywords: Aromatase inhibitor; Arthralgia; Breast cancer; IGF-I; Oestrogens; Tamoxifen.