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12.02.2019 | Preclinical study

Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion

Zeitschrift:
Breast Cancer Research and Treatment
Autoren:
Landry K. Kamdem, Jingyue Xi, Brandi L. Clark, Bryana J. Gregory, Kelley M. Kidwell, Ana-Maria Storniolo, Vered Stearns, Daniel F. Hayes, Christina L. Gersch, James M. Rae, N. Lynn Henry, Daniel L. Hertz
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10549-019-05158-3) contains supplementary material, which is available to authorized users.

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Abstract

Purpose

UGT2B17 gene deletion (UGT2B17*2) has been reported to affect bone health as well as the pharmacokinetics of aromatase inhibitor (AI) drugs such as exemestane. The goal of this study was to assess associations between UGT2B17 gene deletion and bone health prior to and after 24 months of AI treatment in postmenopausal women with hormone receptor positive (HR+) breast cancer.

Methods

Bone health in women with HR+ breast cancer enrolled on the prospective randomized Exemestane and Letrozole Pharmacogenetics (ELPh) trial was determined by measuring bone turnover markers (BTM) and bone mineral density (BMD) pre-treatment and after 3 BTM and 24 BMD months of treatment with either the steroidal AI exemestane or the nonsteroidal AI letrozole. DNA samples were genotyped for UGT2B17*2.

Results

Of the 455 subjects included in the analyses, 244 (53.6%) carried at least one copy of UGT2B17*2. UGT2B17*2 was associated with lower pre-treatment BMD at the hip (P = 0.01) and spine (P = 0.0076). Letrozole treatment was associated with a greater decrease in BMD of the hip (P = 0.03) and spine (P = 0.03) than exemestane. UGT2B17 genotype was not associated with changes in BMD from 24 months of AI treatment, though in UGT2B17*2 homozygous patients, there was a trend toward greater decreases in BMD of the spine from treatment with letrozole compared with exemestane (P = 0.05).

Conclusion

UGT2B17*2 may be associated with lower baseline BMD in women with HR+ breast cancer. Exemestane is less detrimental to bone health than letrozole in postmenopausal women treated with AI, and this effect may be confined to patients carrying UGT2B17*2, though this finding requires independent validation.

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Zusatzmaterial
Consort diagram describing patient flow from trial enrollment to each analysis. Supplementary material 1 (PPTX 184 KB)
10549_2019_5158_MOESM1_ESM.pptx
Literatur
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