title: Clinical Significance of Female-hormones and Cytokines in Breast Cancer Patients Complicated with Aromatase Inhibitor-related Osteoarthropathy - Efficacy of Vitamin E.
abstract: BACKGROUND
  Aromatase inhibitor use for postmenopausal hormone-sensitive breast cancer patients often results in drug-induced osteoarthropathy, while its accurate mechanism has not been clarified. We investigated the implication of female hormones and several cytokines in osteoarthropathy complicated with aromatase inhibitor treatment, and the efficacy of vitamin E on the severity of osteoarthropathy, in breast cancer patients.
  
  
  METHODS
  Sixty two breast cancer patients treated with aromatase inhibitor for average of 1.77 years were included. These patients were orally administered vitamin E (150mg/day) for 29.8 days to alleviate aromatase inhibitor-related osteoarthropathy. Severity of osteoarthropathy was scored, and the patients were grouped based on the severity or vitamin E efficacy. Serum estradiol, progesterone, vitamin E, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), IL-2, IL-4, IL-6, IL-10, and IL-17A concentrations were measured by ELISA or beads array procedures followed by flow cytometry.
  
  
  RESULTS
  There was no significant difference in serum concentrations of the biomarkers between the severe and the mild osteoarthropathy groups before vitamin E administration. The osteoarthropathy scores significantly decreased after vitamin E administration (p=0.0243), while serum-estradiol concentrations did not change. The serum-estradiol concentrations before vitamin E administration in the group sensitive to the vitamin E efficacy were significantly lower, as compared with those in the insensitive group (p=0.0005). The rate of the highly sensitive patients to the vitamin E efficacy in those exhibiting low serum-estradiol concentrations was significantly higher than that in the high serum-estradiol group (p=0.0004). In the sensitive group, serum-estradiol concentrations after taking vitamin E were significantly higher than those before taking vitamin E (p=0.0124).
  
  
  CONCLUSIONS
  Vitamin E administration seemed to be a potential way for relieving osteoarthropathy complicated with aromatase inhibitor use. Using serum-estradiol concentration, it would be possible to select out the breast cancer patients who will respond well to the vitamin E therapy for osteoarthropathy complicated with aromatase inhibitor.
authors.affiliation: 1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Anna
authors.initials: A
authors.lastname: Kiyomi
authors.affiliation: 2. The Cancer Institute Hospital of JFCR, Department of Breast Oncology, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Masujiro
authors.initials: M
authors.lastname: Makita
authors.affiliation: 2. The Cancer Institute Hospital of JFCR, Department of Breast Oncology, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Iwase
authors.affiliation: 1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tanaka
authors.affiliation: 1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Onda
authors.affiliation: 1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Sugiyama
authors.affiliation: 3. Tokyo University of Pharmacy and Life Sciences, Department of Practical Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: 1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Hirano
keywords: aromatase inhibitor-related osteoarthropathy; breast cancer; serum cytokines; serum female hormones; vitamin E