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辅助芳香酶抑制剂治疗与乳腺癌幸存者心血管疾病的早期标志物。

Adjuvant aromatase inhibitor therapy and early markers for cardiovascular disease in breast cancer survivors.

机构信息

Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Breast Cancer Res Treat. 2022 Dec;196(3):591-602. doi: 10.1007/s10549-022-06714-0. Epub 2022 Oct 1.

Abstract

PURPOSE

Aromatase inhibitors (AIs) are an important component of the adjuvant treatment of hormone receptor positive breast cancer (BC) but concerns regarding their cardiovascular safety remain. In this cross-sectional study nested in a breast cancer cohort, we investigated the association between AI exposure and early markers for cardiovascular disease in BC survivors.

METHODS

The study population consisted of 569 women, who were 5-7 years (n = 277) or 10-12 years (n = 292) after BC diagnosis. All participants underwent carotid ultrasound, skin autofluorescence measurement and laboratory evaluation. To quantify AI exposure, we obtained the AI ratio by dividing the duration of AI use by the total duration of endocrine therapy (ET). Patients were classified according to their AI ratio into low (no ET or AI ratio < 0.40), intermediate (0.40 ≤ AI ratio ≤ 0.60) or high AI exposure (AI ratio > 0.60). The association between AI ratio and carotid intima media thickness (cIMT), advanced glycation end products (AGEs) and the presence of dyslipidemia was assessed using linear and logistic regression.

RESULTS

Median age at study visit was 55.5 years (range 45.2-63.8). Forty percent (n = 231) of the study population had used AIs, of whom the majority sequentially with tamoxifen; median duration of AI use was 3.0 years. Mean cIMT and mean AGEs did not differ across AI exposure groups in univariable and multivariable analysis. The occurrence of dyslipidemia did not vary across AI exposure groups. Intermediate AI exposure was associated with more frequent occurrence of the combined endpoint (elevated cIMT, elevated AGEs and/or dyslipidemia). This association, however, was not present in the group with highest AI exposure.

CONCLUSION

AI exposure was not associated with cIMT, AGEs or the presence of dyslipidemia. These results do not prompt a change in current clinical practice, although further research is warranted to validate our findings over time and in different BC populations. Trial registration number (clinicaltrials.gov): NCT02485626, June 30, 2015.

摘要

目的

芳香化酶抑制剂(AIs)是激素受体阳性乳腺癌(BC)辅助治疗的重要组成部分,但人们对其心血管安全性仍存在担忧。在这项嵌套在乳腺癌队列中的横断面研究中,我们研究了 AI 暴露与 BC 幸存者心血管疾病早期标志物之间的关系。

方法

研究人群由 569 名女性组成,她们在 BC 诊断后 5-7 年(n=277)或 10-12 年(n=292)。所有参与者都接受了颈动脉超声、皮肤自发荧光测量和实验室评估。为了量化 AI 暴露,我们通过将 AI 使用时间除以内分泌治疗(ET)总时间来获得 AI 比值。根据 AI 比值,患者被分为低(无 ET 或 AI 比值<0.40)、中(0.40≤AI 比值≤0.60)或高 AI 暴露(AI 比值>0.60)。使用线性和逻辑回归评估 AI 比值与颈动脉内膜中层厚度(cIMT)、晚期糖基化终产物(AGEs)和血脂异常的存在之间的关系。

结果

研究时的中位年龄为 55.5 岁(范围 45.2-63.8)。40%(n=231)的研究人群使用过 AI,其中大多数人序贯使用他莫昔芬;AI 使用的中位时间为 3.0 年。在单变量和多变量分析中,AI 暴露组的 cIMT 和 AGEs 平均值没有差异。AI 暴露组的血脂异常发生率没有差异。中等 AI 暴露与更频繁的联合终点(cIMT 升高、AGEs 升高和/或血脂异常)相关。然而,这种关联在 AI 暴露最高的组中并不存在。

结论

AI 暴露与 cIMT、AGEs 或血脂异常无关。这些结果不会改变当前的临床实践,尽管需要进一步的研究来随着时间的推移和在不同的 BC 人群中验证我们的发现。试验注册编号(clinicaltrials.gov):NCT02485626,2015 年 6 月 30 日。

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