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Ki-67 是一种核蛋白，这种蛋白在细胞准备分裂（细胞增殖）时增加。 使用 Ki-67 抗体进行免疫组化(IHC)可以检测 Ki-67 阳性肿瘤组织切片中肿瘤细胞的百分比。 Ki-67 阳性细胞越多，处于细胞分裂期的细胞就越多，说明癌症可能处于进展期，早期复发的可能性增加。^1,2

monarchE 临床试验是首次对接受辅助治疗的乳腺癌患者开展的前瞻性大型随机临床试验，旨在对以 Ki-67≥20% 作为生物标志物进行评价。 样本经过了集中评估，评估时使用了甲基化抑制结合蛋白(MIB-1) Ki-67 抗体，以及 新型特异性、精确、稳定的 Ki-67 IHC 检测技术。^3-7 

关于在monarchE 中使用的Ki-67 生物标志物检测的详细信息可在单独的医学信函中获得，并可应要求提供。

由于国际上对于 Ki-67 临界值的高低尚未形成共识，于是根据历史数据和 St. Gallen 的指南选择 ≥20% 作为了阈值。⁶ 

monarchE 研究中采用的附加终点包括评估肿瘤 Ki-67 高表达（≥ 20%）或低表达（<20%）患者的有效性。⁶ 

上次审阅日期：2024年1月30日

参考文献

1. Fasching PA, Gass P, Häberle L, et al. Prognostic effect of Ki-67 in common clinical subgroups of patients with HER2-negative, hormone receptor-positive early breast cancer. Breast Cancer Res Treat. 2019;175(3):617-625. http://dx.doi.org/10.1007/s10549-019-05198-9

2. Dowsett M, Nielsen TO, A'Hern R, et al. Assessment of Ki67 in breast cancer: recommendations from the international Ki67 in breast cancer working group. J Natl Cancer Inst. 2011;103(22):1656-1664. https://doi.org/10.1093/jnci/djr393

3. Polewski MD, Nielsen GB, Tabuena-Frolli ST, et al. External reproducibility of an analytically validated immunohistochemistry assay for detection of Ki-67 expression in breast carcinomas. Arch Pathol Lab Med. 2020;144(9 suppl 1):e183. College of American Pathologists abstract 400-68. http://dx.doi.org/10.5858/arpa.2020-0991-AB

4. Nielsen G, Gu Y, Weaver A, et al. Development of a novel clinical trial immunohistochemistry (IHC) assay using Ki-67, clone MIB-1, monoclonal antibody for Dako Omnis. Virchows Archive. 2020;477:(suppl 1):S52. Congress of the European Society of Pathology and International Congress of the International Academy of Pathology abstract PS-01-045. https://doi.org/10.1007/s00428-020-02938-x

5. Polewski MD, Nelsen GB, Gu Y, et al. A standardized investigational Ki-67 immunohistochemistry assay used to assess high-risk early breast cancer patients in the monarchE phase 3 clinical study identifies a population with greater risk of disease recurrence when treated with endocrine therapy alone. Appl Immunohistochem Mol Morphol. 2022;30(4):237-245. https://doi.org/10.1097/PAI.0000000000001009

6. Harbeck N, Johnston S, Fasching P, et al. High Ki-67 as a biomarker for identifying patients with high risk early breast cancer treated in monarchE. Poster presented at: 43rd Annual San Antonio Breast Cancer Symposium (SABCS Virtual); December 8-11, 2020. http://www.sabcs.org/Portals/SABCS2016/PD2%2001%20Nadia%20Harbeck.pdf?ver=2021-08-29-125001-927

7. Komforti M, Downs-Kelly E, Sapunar F, et al. Two instrument comparison of reagents from a US FDA-approved assay for the assessment of Ki-67 in high-risk early breast cancer. Appl Immunohistochem Mol Morphol. 2022;30(8):577-583. https://journals.lww.com/appliedimmunohist/Fulltext/2022/09000/Two_Instrument_Comparison_of_Reagents_From_a_US.7.aspx