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 |
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| Affiliation: | 1. Oncology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;2. Laboratory Medicine, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;3. Laboratory of Clinical and Experimental Endocrinology, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;4. Gynecology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;5. Electrical Engineering (ESAT-SISTA), KU Leuven, Herestraat 49, 3000 Leuven, Belgium;6. Multidisciplinary Breast Center, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;7. General Medical Oncology, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium;8. Cardiovascular Sciences, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;1. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland;2. Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland;3. Department of Oncology, Hôpital Saint-Antoine, Paris, France;4. University Pierre et Marie Curie, Paris VI, Paris, France;5. University of Helsinki, Helsinki, Finland;6. STAT-Consulting, Nokia, Finland;7. International Drug Development Institute (IDDI), Louvain-la-Neuve, Belgium;1. Department of Medical Oncology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, China;2. Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu 210002, China;1. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Japan;2. Department of Thoracic Surgery, Graduate School of Medicine, Kyoto University, Japan;3. Department of Biomedical Statistics and Bioinformatics, Graduate School of Medicine, Kyoto University, Japan;4. Department of Radiation Oncology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan;1. Adult Mesenchymal Tumor Medical Oncology Unit, Cancer Medicine Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;2. Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;3. Medical Oncology Unit ‘Sandro Pitigliani’, S. Stefano Civil Hospital, Prato, Italy;4. Medical Oncology, IRCCS – Istituto di Candiolo, Candiolo, Italy;5. Department of Oncology, Hematology and Respiratory Diseases, University of Modena and Reggio Emilia, Modena, Italy;6. Department of Oncology, University Hospital of Palermo, Palermo, Italy;7. Department of Radiology, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;8. Department of Anatomic Pathology, General Hospital of Treviso, Treviso, Italy;9. Pharmacy Unit, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;10. Melanoma and Sarcoma Unit, Department of Surgery, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;11. Melanoma and Sarcoma, Surgery Department, Istituto Europeo di Oncologia, Milan, Italy;12. Laboratory of Experimental Molecular Pathology, Department of Diagnostic Pathology and Laboratory, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy;1. Institute of Pathology, Charité University Medicine Berlin, Charitéplatz 1, 10117 Berlin, Germany;2. Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany;3. Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 220/221, 69120 Heidelberg, Germany;4. Tissue Bank of the National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany;5. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer 581, 69120 Heidelberg, Germany;6. Institute of Pathology, SLK-Clinics Heilbronn, Am Gesundbrunnen 20-26, 74078 Heilbronn, Germany;1. Department of Gastroenterology and Digestive Oncology, University Hospital of St Etienne, University Jean Monnet, LINA EA 4624, France;2. Radiotherapy Department, University Hospital Haut Lévêque Bordeaux, France;3. Department of Gastroenterology, University Hospital Le Bocage, Dijon, France;4. Fédération Francophone de Cancérologie Digestive, Dijon, France;5. Université de Lyon, F-69000 Lyon, France;6. Université Lyon 1, CNRS, UMR5558, Laboratoire de Biométrie et Biologie Evolutive, F-69622 Villeurbanne, France;7. Hospices Civils de Lyon, Service de Biostatistique, F-69003 Lyon, France;8. Department of Gastroenterology, University Hospital North, Marseille, France;9. Oncology Department, University Hospital, Rouen, France;10. Oncology Department, University Hospital Saint-André, Bordeaux, France;11. Department of Gastroenterology and Digestive Oncology, University Hospital La Timone, Marseille, France;12. Department of Gastroenterology, Hospital of Charleville-Mezieres, France;13. Radiotherapy, Boulogne, France;14. Oncology Department, René Gauducheau Center, St Herblain, France;15. Hospital of Tarbes, France;p. Oncology Department, Hospital of Valenciennes, France;q. Radiotherapy Department, Center Georges-François Leclerc, Dijon, France;r. Department of Medical Oncology, University Hospital Amiens, France |
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| Abstract: | BackgroundAromatase 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 methodsPostmenopausal 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 12 months of therapy.Results84 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 6 months (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).ConclusionThese findings provide preliminary evidence that AI-induced musculoskeletal symptoms are associated with changes in the growth hormone (GH)/IGF-I axis. |
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| Keywords: | Breast cancer Aromatase inhibitor Tamoxifen Arthralgia IGF-I Oestrogens |
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