title: 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.
  
  
  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).
  
  
  CONCLUSIONS
  These findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis.
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: anneleen.lintermans@uzleuven.be.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Lintermans
authors.affiliation: Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Vanderschueren
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Verhaeghe
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Van Asten
authors.affiliation: Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Ivo
authors.initials: I
authors.lastname: Jans
authors.affiliation: Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Van Herck
authors.affiliation: Electrical Engineering (ESAT-SISTA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Annouschka
authors.initials: A
authors.lastname: Laenen
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Paridaens
authors.affiliation: Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Jaak
authors.initials: J
authors.lastname: Billen
authors.affiliation: Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Pauwels
authors.affiliation: Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vermeersch
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: Wildiers
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Marie-Rose
authors.initials: MR
authors.lastname: Christiaens
authors.affiliation: Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium; Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium; Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Electronic address: patrick.neven@uzleuven.be.
authors.forename: Patrick
authors.initials: P
authors.lastname: Neven
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000970:Antineoplastic Agents / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects; D047072:Aromatase Inhibitors / Q000009:adverse effects*; D018771:Arthralgia / Q000097:blood / Q000139:chemically induced*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D000077289:Letrozole; D008875:Middle Aged; D059352:Musculoskeletal Pain / Q000139:chemically induced; D009570:Nitriles / Q000009:adverse effects; D011446:Prospective Studies; D013629:Tamoxifen / Q000009:adverse effects*; D014230:Triazoles / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004967:Estrogens; D018972:Insulin-Like Growth Factor Binding Protein 3; D009570:Nitriles; D014230:Triazoles; D013629:Tamoxifen; D000077384:Anastrozole; D007334:Insulin-Like Growth Factor I; D000077289:Letrozole
keywords: Aromatase inhibitor; Arthralgia; Breast cancer; IGF-I; Oestrogens; Tamoxifen