J Cancer 2015; 6(4):367-376. doi:10.7150/jca.10695

Research Paper

Clinical Significance of Female-hormones and Cytokines in Breast Cancer Patients Complicated with Aromatase Inhibitor-related Osteoarthropathy - Efficacy of Vitamin E

Anna Kiyomi1✉, Masujiro Makita2, Takuji Iwase2, Sachiko Tanaka1, Kenji Onda1, Kentaro Sugiyama1, Hironori Takeuchi3, Toshihiko Hirano1

1. Tokyo University of Pharmacy and Life Sciences, Department of Clinical Pharmacology, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan
2. The Cancer Institute Hospital of JFCR, Department of Breast Oncology, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan
3. Tokyo University of Pharmacy and Life Sciences, Department of Practical Pharmacy, 1432-1 Horinouchi, Hachioji, Tokyo 192-0355, Japan

Abstract

Introduction: 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.

Keywords: aromatase inhibitor-related osteoarthropathy, breast cancer, vitamin E, serum female hormones, serum cytokines

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How to cite this article:
Kiyomi A, Makita M, Iwase T, Tanaka S, Onda K, Sugiyama K, Takeuchi H, Hirano T. Clinical Significance of Female-hormones and Cytokines in Breast Cancer Patients Complicated with Aromatase Inhibitor-related Osteoarthropathy - Efficacy of Vitamin E. J Cancer 2015; 6(4):367-376. doi:10.7150/jca.10695. Available from http://www.jcancer.org/v06p0367.htm