Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole
Effects of SLCO1B1 polymorphisms on plasma estrogen concentrations in women with breast cancer receiving aromatase inhibitors exemestane and letrozole
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DOI：
10.2217/pgs-2019-0020
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发表时间：
2019-06-01
期刊：
影响因子：
2.1
通讯作者：
Hertz, Daniel L.
中科院分区：
文献类型：
--
作者：
Dempsey, Jacqueline M.;Kidwell, Kelley M.;Hertz, Daniel L.
目的：本研究检测了SLCO1B1多态性与接受来曲唑或阿司美坦治疗的乳腺癌妇女的循环雌激素水平之间的相关性。患者与方法：对绝经后乳腺癌患者进行SLCO1B1*5（rs4149056）和rs10841753基因分型。测量治疗前和治疗中血浆雌激素和芳香化酶抑制剂（AI）浓度。进行回归分析，以测试与雌激素和药物浓度的药物遗传学关联。结果：SLCO 1B1 *5与治疗前硫酸雌酮水平升高以及AI治疗3个月后可检测到雌酮浓度的风险增加相关。结论：这些发现表明SLCO1B1多态性可能对AI治疗的雌激素反应有影响，因此可能对这些药物的抗癌有效性产生不利影响。
Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (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. Results:SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.