芳香化酶抑制剂依西美坦和来曲唑治疗乳腺癌患者中基因多态性对血浆雌激素浓度的影响。
Effects of polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole.
机构信息
Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, MI 48109-1065, USA.
Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, USA.
出版信息
Pharmacogenomics. 2019 Jun;20(8):571-580. doi: 10.2217/pgs-2019-0020.
Abstract
This study tested for associations between polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Postmenopausal women with hormone-receptor positive breast cancer were genotyped for (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3 months of AI treatment. These findings suggest polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.
摘要
本研究旨在检测乳腺癌患者接受来曲唑或依西美坦治疗时， 基因多态性与循环雌激素水平之间的相关性。对激素受体阳性乳腺癌的绝经后女性进行 （rs4149056）和 rs10841753 基因分型。测定预处理和治疗期间的血浆雌激素和芳香化酶抑制剂（AI）浓度。采用回归分析检测与雌激素和药物浓度的药物遗传学相关性。 与预处理雌酮硫酸盐升高以及 AI 治疗 3 个月后可检测到雌酮浓度的风险增加相关。这些发现表明 基因多态性可能对 AI 治疗的雌激素反应产生影响，从而可能对这些药物的抗癌效果产生不利影响。
相似文献
1
Effects of polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole.
Pharmacogenomics. 2019 Jun;20(8):571-580. doi: 10.2217/pgs-2019-0020.
2
Exemestane may be less detrimental than letrozole to bone health in women homozygous for the UGT2B17*2 gene deletion.
Breast Cancer Res Treat. 2019 Jun;175(2):297-303. doi: 10.1007/s10549-019-05158-3. Epub 2019 Feb 12.
3
Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer.
Breast Cancer Res Treat. 2017 Feb;161(3):453-461. doi: 10.1007/s10549-016-4077-4. Epub 2016 Dec 9.
4
Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial.
Lancet Oncol. 2018 Apr;19(4):474-485. doi: 10.1016/S1470-2045(18)30116-5. Epub 2018 Feb 23.
5
Superior suppression of serum estrogens during neoadjuvant breast cancer treatment with letrozole compared to exemestane.
Breast Cancer Res Treat. 2024 Jul;206(2):347-358. doi: 10.1007/s10549-024-07313-x. Epub 2024 Apr 23.
6
Changes in serum estrogenic activity during neoadjuvant therapy with letrozole and exemestane.
J Steroid Biochem Mol Biol. 2020 Jun;200:105641. doi: 10.1016/j.jsbmb.2020.105641. Epub 2020 Mar 6.
7
Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer.
J Clin Oncol. 2012 Aug 20;30(24):2977-80. doi: 10.1200/JCO.2012.42.0273. Epub 2012 Jul 16.
8
Comparison of changes in the lipid profile of postmenopausal women with early stage breast cancer treated with exemestane or letrozole.
J Clin Pharmacol. 2012 Dec;52(12):1852-60. doi: 10.1177/0091270011424153. Epub 2011 Dec 15.
9
Sequential treatment with exemestane and non-steroidal aromatase inhibitors in advanced breast cancer.
Oncology. 2005;69(6):471-7. doi: 10.1159/000090985. Epub 2006 Jan 12.
10
Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.
Breast Cancer Res Treat. 2015 Nov;154(2):263-73. doi: 10.1007/s10549-015-3608-8. Epub 2015 Nov 4.
引用本文的文献
1
Differential Expression Patterns of SLCO Solute Carriers in Human Breast Cancer Cell Lines and Tumour Samples.
J Cell Mol Med. 2025 Sep;29(17):e70838. doi: 10.1111/jcmm.70838.
2
OATP1B-type Transport Function Is a Determinant of Aromatase Inhibitor-Associated Arthralgia Susceptibility.
Cancer Res Commun. 2025 Mar 1;5(3):496-510. doi: 10.1158/2767-9764.CRC-24-0475.
3
Association between SLCO1B1 genetic polymorphisms and bleeding risk in patients treated with edoxaban.
Sci Rep. 2023 Sep 25;13(1):15967. doi: 10.1038/s41598-023-43179-7.
4
The effect of genetic variation in estrogen transportation and metabolism on the severity of menopause symptoms: A study from the RIGHT 10K cohort.
Maturitas. 2023 Oct;176:107797. doi: 10.1016/j.maturitas.2023.107797. Epub 2023 Aug 16.
5
Development and Validation of an ADME-Related Gene Signature for Survival, Treatment Outcome and Immune Cell Infiltration in Head and Neck Squamous Cell Carcinoma.
Front Immunol. 2022 Jul 8;13:905635. doi: 10.3389/fimmu.2022.905635. eCollection 2022.
6
Genetic Influences in Breast Cancer Drug Resistance.
Breast Cancer (Dove Med Press). 2021 Feb 9;13:59-85. doi: 10.2147/BCTT.S284453. eCollection 2021.
本文引用的文献
1
Association of *14 Allele with Poor Response to Methotrexate in Juvenile Idiopathic Arthritis Patients.
ACR Open Rheumatol. 2019 Mar 15;1(1):58-62. doi: 10.1002/acr2.1008. eCollection 2019 Mar.
2
Letrozole concentration is associated with CYP2A6 variation but not with arthralgia in patients with breast cancer.
Breast Cancer Res Treat. 2018 Nov;172(2):371-379. doi: 10.1007/s10549-018-4910-z. Epub 2018 Aug 9.
3
Impact of the OATP1B1 c.521T>C single nucleotide polymorphism on the pharmacokinetics of exemestane in healthy post-menopausal female volunteers.
J Clin Pharm Ther. 2017 Oct;42(5):547-553. doi: 10.1111/jcpt.12569. Epub 2017 Jul 29.
4
Variable aromatase inhibitor plasma concentrations do not correlate with circulating estrogen concentrations in post-menopausal breast cancer patients.
Breast Cancer Res Treat. 2017 Oct;165(3):659-668. doi: 10.1007/s10549-017-4346-x. Epub 2017 Jun 22.
5
Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors.
Breast Cancer Res Treat. 2017 Jul;164(2):411-419. doi: 10.1007/s10549-017-4260-2. Epub 2017 Apr 27.
6
SLCO1B1 polymorphisms and plasma estrone conjugates in postmenopausal women with ER+ breast cancer: genome-wide association studies of the estrone pathway.
Breast Cancer Res Treat. 2017 Jul;164(1):189-199. doi: 10.1007/s10549-017-4243-3. Epub 2017 Apr 20.
7
Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.
Pharmacogenomics. 2017 Apr;18(5):481-499. doi: 10.2217/pgs-2016-0205. Epub 2017 Mar 27.
8
Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial.
J Clin Oncol. 2017 Apr 1;35(10):1041-1048. doi: 10.1200/JCO.2016.69.2871. Epub 2017 Jan 23.
9
Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer.
Breast Cancer Res Treat. 2017 Feb;161(3):453-461. doi: 10.1007/s10549-016-4077-4. Epub 2016 Dec 9.
10
Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials.
Lancet. 2015 Oct 3;386(10001):1341-1352. doi: 10.1016/S0140-6736(15)61074-1. Epub 2015 Jul 23.
Zotero 插件