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血液标志物在预测乳腺癌患者生育力保存结局中的应用。

Utility of Blood Markers for Predicting Outcomes of Fertility Preservation in Patients With Breast Cancer.

机构信息

Department of Obstetrics and Gynecology, Seoul National University Bundang Hospital, Seongnam, South Korea.

Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea.

出版信息

Front Endocrinol (Lausanne). 2022 Feb 23;13:803803. doi: 10.3389/fendo.2022.803803. eCollection 2022.

Abstract

This study aimed to investigate the usability of blood markers for predicting controlled ovarian stimulation (COS) outcomes in patients with breast cancer undergoing fertility preservation (FP). In total, 91 patients with breast cancer who had undergone COS using a letrozole-combined gonadotropin-releasing hormone (GnRH) antagonist protocol before chemotherapy were enrolled retrospectively in a single tertiary hospital. FP outcomes were compared in terms of the mean platelet volume (MPV), MPV/platelet count (PC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR). The cutoff values for obtaining 10 or more mature oocytes as favorable prognoses were obtained for each parameter, and the COS outcomes were compared based on the cutoff values. The optimal cutoff levels for MPV and MPV/PC were 10.15 [sensitivity: 90.0%; specificity: 45.1%; AUC: 0.687; 95% CI (0.563, 0.810)] and 0.41 [sensitivity: 65.0%; specificity: 67.6%; AUC: 0.682; 95% CI (0.568, 0.796)], respectively. The oocyte numbers did not significantly differ with respect to the cutoff values of NLR, PLR, and LMR (p > 0.05). However, the total number of acquired and mature oocytes were significantly lower in the group with MPV<10.15 than in that with MPV≥10.15 (8.0 ± 5.1 12.6 ± 9.1, p=0.003; 4.0 ± 3.7 7.3 ± 6.3, p=0.002, respectively). Similarly, considering the cutoff of MPV/PC as 0.41, the low-MPV/PC group showed a significantly lower total oocyte yield than the high-MPV/PC group (9.5 ± 7.1 13.1 ± 9.1, p=0.048), whereas the number of mature oocytes showed similar patterns with no statistical significance (5.3 ± 5.4 7.3 ± 6.1, p=0.092). From logistic regression analysis, age, anti-Müllerian hormone (AMH) level, MPV, and MPV/PC≥0.41 were found to be significant factors for the acquisition of 10 or more MII oocytes (p=0.049, OR: 0.850; p<0.001, OR: 1.622; p=0.018, OR: 3.184; p=0.013, OR: 9.251, respectively). MPV or MPV/PC can be a reliable marker for predicting FP outcome in patients with breast cancer. Protocols to acquire more mature oocytes, such as the dual-trigger approach, could be recommended for patients with breast cancer with MPV<10.15. Furthermore, a higher dose of gonadotropins was considered to obtain more oocytes in patients with MPV/PC<0.41.

摘要

本研究旨在探讨血液标志物在预测接受生育力保存(FP)的乳腺癌患者控制性卵巢刺激(COS)结局方面的可用性。回顾性分析了在一家三级医院接受来曲唑联合促性腺激素释放激素(GnRH)拮抗剂方案进行 COS 的 91 例乳腺癌患者,这些患者在化疗前接受了 COS。比较了不同的血小板平均体积(MPV)、MPV/血小板计数(PC)、中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)和淋巴细胞与单核细胞比值(LMR)在预测 FP 结局方面的可用性。对于每个参数,获得 10 个或更多成熟卵母细胞的有利预后的截止值被获得,并基于该截止值比较了 COS 结局。MPV 和 MPV/PC 的最佳截断值分别为 10.15 [灵敏度:90.0%;特异性:45.1%;AUC:0.687;95%CI(0.563,0.810)]和 0.41 [灵敏度:65.0%;特异性:67.6%;AUC:0.682;95%CI(0.568,0.796)]。NLR、PLR 和 LMR 的截止值与卵母细胞数量没有显著差异(p>0.05)。然而,MPV<10.15 组的总获得和成熟卵母细胞数量明显低于 MPV≥10.15 组(8.0±5.1 12.6±9.1,p=0.003;4.0±3.7 7.3±6.3,p=0.002)。同样,考虑到 MPV/PC 的截断值为 0.41,低 MPV/PC 组的总卵母细胞产量明显低于高 MPV/PC 组(9.5±7.1 13.1±9.1,p=0.048),而成熟卵母细胞数量则表现出类似的模式,无统计学意义(5.3±5.4 7.3±6.1,p=0.092)。通过逻辑回归分析,发现年龄、抗苗勒管激素(AMH)水平、MPV 和 MPV/PC≥0.41 是获得 10 个或更多 MII 卵母细胞的显著因素(p=0.049,OR:0.850;p<0.001,OR:1.622;p=0.018,OR:3.184;p=0.013,OR:9.251,分别)。MPV 或 MPV/PC 可作为预测乳腺癌患者 FP 结局的可靠标志物。对于 MPV<10.15 的乳腺癌患者,可以推荐使用双触发方法等方案来获得更多成熟的卵母细胞。此外,考虑到 MPV/PC<0.41 的患者需要获得更多的卵母细胞,建议增加促性腺激素的剂量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09c1/8905649/8ebd7dfe035b/fendo-13-803803-g001.jpg

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