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监测接受五年他莫昔芬辅助治疗后延长来曲唑辅助治疗的乳腺癌患者的血清雌二醇水平:一项前瞻性试验。

Monitoring serum estradiol levels in breast cancer patients during extended adjuvant letrozole treatment after five years of tamoxifen: a prospective trial.

机构信息

Comprehensive Cancer Center, Helsinki University Hospital, PO Box 180, 00290, Helsinki, Finland.

Department of Obstetrics and Gynecology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

出版信息

Breast Cancer Res Treat. 2021 Jun;187(3):769-775. doi: 10.1007/s10549-021-06168-w. Epub 2021 Mar 12.

Abstract

PURPOSE

To analyze whether monitoring serum estradiol (E2) levels using a highly sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) method may identify patients with AI failure with E2 levels below the lower limit of quantification (LLOQ) after schwitching from tamoxifen to letrozole.

METHODS

In a prospective study of breast cancer patients switching to letrozole treatment after previous tamoxifen, plasma estrogen levels were measured at baseline and after 3- and 12-months using LC-MS/MS.

RESULTS

Forty-six patients were classified postmenopausal and entered into the final analysis. Thirty-nine (85%) patients had three- and 12-month E2 concentrations below the LLOQ (5 pmol/L). In the seven patients classified as AI-failures during letrozole treatment, serum E2-MS level rose above 5 pmol/L at 3 months with a mean E2-MS 77.5 pmol/L or 12 months with a mean E2-MS 21 pmol/L. None of the baseline variables i.e., age at diagnosis, age at study entry, age at menarche, BMI, endometrial thickness, total ovarian volume, baseline FSH, E2-IA, or E2-MS were significantly associated with the risk of AI failure in logistic regression. E2 levels at baseline measured by E2-IA did not significantly correlate to the levels measured by E2-MS.

CONCLUSIONS

There is a relatively high risk of inadequate estrogen suppression in patients who switch from tamoxifen treatment to AIs. The use of sensitive and specific assays, such as LC-MS/MS methods, to monitor estrogen levels during AI treatment is essential to minimize the risk of a proceeding inefficient endocrine therapy.

摘要

目的

分析在从他莫昔芬转换为来曲唑后,使用高灵敏度和特异性的液相色谱串联质谱(LC-MS/MS)方法监测血清雌二醇(E2)水平是否可以识别雌二醇水平低于定量下限(LLOQ)的 AI 失败患者。

方法

在一项对接受来曲唑治疗的乳腺癌患者进行的前瞻性研究中,在基线时以及 3 个月和 12 个月时使用 LC-MS/MS 测量血浆雌激素水平。

结果

46 名患者被分类为绝经后,并纳入最终分析。39 名(85%)患者在 3 个月和 12 个月时 E2 浓度低于 LLOQ(5 pmol/L)。在来曲唑治疗期间被分类为 AI 失败的 7 名患者中,血清 E2-MS 水平在 3 个月时升高至 5 pmol/L 以上,平均 E2-MS 为 77.5 pmol/L,或在 12 个月时升高至 21 pmol/L。在逻辑回归中,没有任何基线变量(即诊断时年龄、研究入组时年龄、初潮年龄、BMI、子宫内膜厚度、总卵巢体积、基线 FSH、E2-IA 或 E2-MS)与 AI 失败的风险显著相关。E2-IA 测量的基线 E2 水平与 E2-MS 测量的水平无显著相关性。

结论

从他莫昔芬治疗转换为 AI 治疗的患者中,存在雌激素抑制不足的相对较高风险。在 AI 治疗期间使用敏感和特异性的检测方法,如 LC-MS/MS 方法,监测雌激素水平对于降低内分泌治疗无效的风险至关重要。

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