Abstract:
:Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Oesterreich S,Henry NL,Kidwell KM,Van Poznak CH,Skaar TC,Dantzer J,Li L,Hangartner TN,Peacock M,Nguyen AT,Rae JM,Desta Z,Philips S,Storniolo AM,Stearns V,Hayes DF,Flockhart DAdoi
10.1007/s10549-015-3608-8subject
Has Abstractpub_date
2015-11-01 00:00:00pages
263-73issue
2eissn
0167-6806issn
1573-7217pii
10.1007/s10549-015-3608-8journal_volume
154pub_type
杂志文章abstract::Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-fa...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
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doi:10.1007/BF02235745
更新日期:1985-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2012-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
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更新日期:2010-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01806232
更新日期:1983-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01810740
更新日期:1989-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05396-5
更新日期:2019-11-01 00:00:00
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journal_title:Breast cancer research and treatment
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更新日期:1998-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4207-7
更新日期:2017-06-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1023/a:1006289811540
更新日期:1999-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9718-1
更新日期:2008-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2018-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-013-2764-y
更新日期:2013-12-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05416-4
更新日期:2019-12-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1734-5
更新日期:2012-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2679-7
更新日期:2013-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2009-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-007-9746-x
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journal_title:Breast cancer research and treatment
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-011-1506-2
更新日期:2011-09-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF01834637
更新日期:1992-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3610-1
更新日期:2015-11-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666166
更新日期:1994-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2012-04-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-015-3287-5
更新日期:2015-02-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章
doi:10.1007/s10549-012-2223-1
更新日期:2012-10-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1024443303436
更新日期:2003-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
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更新日期:2016-11-01 00:00:00