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

Landry K. Kamdem, Jingyue Xi, Brandi L. Clark, Bryana J. Gregory, Kelley M. Kidwell, Anna Maria Storniolo, Vered Stearns, Daniel F. Hayes, Christina L. Gersch, James M. Rae, N. Lynn Henry, Daniel L. Hertz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalBreast Cancer Research and Treatment
DOIs
StatePublished - Jan 1 2019

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exemestane
letrozole
Gene Deletion
Women's Health
Aromatase Inhibitors
Bone Density
Bone and Bones
Spine
Bone Remodeling
Breast Neoplasms
Therapeutics
Hip
Health
Pharmacogenetics

Keywords

  • Bone health
  • Endocrine therapy
  • Hormone receptor positive Breast Cancer
  • UGT2B17

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion. / Kamdem, Landry K.; Xi, Jingyue; Clark, Brandi L.; Gregory, Bryana J.; Kidwell, Kelley M.; Storniolo, Anna Maria; Stearns, Vered; Hayes, Daniel F.; Gersch, Christina L.; Rae, James M.; Henry, N. Lynn; Hertz, Daniel L.

In: Breast Cancer Research and Treatment, 01.01.2019.

Research output: Contribution to journalArticle

Kamdem, Landry K. ; Xi, Jingyue ; Clark, Brandi L. ; Gregory, Bryana J. ; Kidwell, Kelley M. ; Storniolo, Anna Maria ; Stearns, Vered ; Hayes, Daniel F. ; Gersch, Christina L. ; Rae, James M. ; Henry, N. Lynn ; Hertz, Daniel L. / Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion. In: Breast Cancer Research and Treatment. 2019.
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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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author = "Kamdem, {Landry K.} and Jingyue Xi and Clark, {Brandi L.} and Gregory, {Bryana J.} and Kidwell, {Kelley M.} and Storniolo, {Anna Maria} and Vered Stearns and Hayes, {Daniel F.} and Gersch, {Christina L.} and Rae, {James M.} and Henry, {N. Lynn} and Hertz, {Daniel L.}",
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T1 - Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion

AU - Kamdem, Landry K.

AU - Xi, Jingyue

AU - Clark, Brandi L.

AU - Gregory, Bryana J.

AU - Kidwell, Kelley M.

AU - Storniolo, Anna Maria

AU - Stearns, Vered

AU - Hayes, Daniel F.

AU - Gersch, Christina L.

AU - Rae, James M.

AU - Henry, N. Lynn

AU - Hertz, Daniel L.

PY - 2019/1/1

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N2 - 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.

AB - 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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KW - Hormone receptor positive Breast Cancer

KW - UGT2B17

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