{"title":"MCM-2水平作为根据TAILORx分类预测高危乳腺癌患者的潜在生物标志物","authors":"Çağlar Ünal, Tolga Özmen, Ahmet Serkan İlgün, Çetin Ordu, Enver Özkurt, Naziye Ak, Gül Alço, Zeynep Erdoğan İyigün, Sevgi Kurt, Tomris Duymaz, Mehmet Alper Öztürk, Filiz Elbüken Çelebi, Kanay Yararbaş, Gürsel Soybir, Fatma Aktepe, Vahit Özmen","doi":"10.2147/BCTT.S421535","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The minichromosome maintenance protein-2 (MCM-2) is a more sensitive proliferation marker than Ki-67. This study aimed to evaluate the relationship between MCM-2 and Oncotype DX recurrence score (ODX-RS) and determine an MCM-2 cutoff value in high-risk patients according to TAILORx risk categorization.</p><p><strong>Methods: </strong>Hormone receptor (HR) positive HER-2 negative early-stage breast cancer patients (pT1-2, pN0-N1, M0) who had ODX-RS were included in the study. According to the TAILORx trial, patients were divided into two groups with high (ODX-RS ≥26) and low risk (ODX-RS <26) in terms of ODX-RS. Formalin-fixed-paraffin-embedded tissues of patients were re-evaluated, and 3 µm sections were prepared for MCM-2 immuno-histochemical staining. The relationship between ODX-RS and the percentage of MCM-2 staining was evaluated in two groups. The ROC curve analysis was performed to determine the MCM-2 cut-off value for the TAILORx high-risk group (ODX-RS ≥26).</p><p><strong>Results: </strong>The mean MCM-2 value was significantly higher in the high-risk group [(60.2 ± 11.2 vs 34.4 ± 13.8, p < 0.001)]. In the multivariate analysis, MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003) and progesterone receptor (PR) levels ≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003) were found to be independent factors indicating a high-risk group. A one-unit increase in MCM-2 level increased the likelihood of being in the high-risk group by 1.27 times. In the ROC curve analysis, the optimal MCM-2 cut-off level was 50 (AUC: 0.921, sensitivity: 86.7%, specificity: 96.0%, p < 0.001).</p><p><strong>Conclusion: </strong>Our study is the first study in the literature to investigate the relationship between ODX-RS and MCM-2 levels in HR-positive HER-2 negative early breast-cancer patients. In this study, MCM-2 was an independent risk factor in identifying high-risk patients according to TAILORx risk classification. MCM 2 cut-off value (50) may help the decision on adjuvant chemotherapy in patients where the Oncotype DX test cannot be performed.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/9e/bctt-15-659.PMC10478780.pdf","citationCount":"1","resultStr":"{\"title\":\"MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification.\",\"authors\":\"Çağlar Ünal, Tolga Özmen, Ahmet Serkan İlgün, Çetin Ordu, Enver Özkurt, Naziye Ak, Gül Alço, Zeynep Erdoğan İyigün, Sevgi Kurt, Tomris Duymaz, Mehmet Alper Öztürk, Filiz Elbüken Çelebi, Kanay Yararbaş, Gürsel Soybir, Fatma Aktepe, Vahit Özmen\",\"doi\":\"10.2147/BCTT.S421535\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The minichromosome maintenance protein-2 (MCM-2) is a more sensitive proliferation marker than Ki-67. This study aimed to evaluate the relationship between MCM-2 and Oncotype DX recurrence score (ODX-RS) and determine an MCM-2 cutoff value in high-risk patients according to TAILORx risk categorization.</p><p><strong>Methods: </strong>Hormone receptor (HR) positive HER-2 negative early-stage breast cancer patients (pT1-2, pN0-N1, M0) who had ODX-RS were included in the study. According to the TAILORx trial, patients were divided into two groups with high (ODX-RS ≥26) and low risk (ODX-RS <26) in terms of ODX-RS. Formalin-fixed-paraffin-embedded tissues of patients were re-evaluated, and 3 µm sections were prepared for MCM-2 immuno-histochemical staining. The relationship between ODX-RS and the percentage of MCM-2 staining was evaluated in two groups. The ROC curve analysis was performed to determine the MCM-2 cut-off value for the TAILORx high-risk group (ODX-RS ≥26).</p><p><strong>Results: </strong>The mean MCM-2 value was significantly higher in the high-risk group [(60.2 ± 11.2 vs 34.4 ± 13.8, p < 0.001)]. In the multivariate analysis, MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003) and progesterone receptor (PR) levels ≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003) were found to be independent factors indicating a high-risk group. A one-unit increase in MCM-2 level increased the likelihood of being in the high-risk group by 1.27 times. In the ROC curve analysis, the optimal MCM-2 cut-off level was 50 (AUC: 0.921, sensitivity: 86.7%, specificity: 96.0%, p < 0.001).</p><p><strong>Conclusion: </strong>Our study is the first study in the literature to investigate the relationship between ODX-RS and MCM-2 levels in HR-positive HER-2 negative early breast-cancer patients. In this study, MCM-2 was an independent risk factor in identifying high-risk patients according to TAILORx risk classification. MCM 2 cut-off value (50) may help the decision on adjuvant chemotherapy in patients where the Oncotype DX test cannot be performed.</p>\",\"PeriodicalId\":9106,\"journal\":{\"name\":\"Breast Cancer : Targets and Therapy\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/9e/bctt-15-659.PMC10478780.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Breast Cancer : Targets and Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/BCTT.S421535\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Breast Cancer : Targets and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/BCTT.S421535","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 1
摘要
背景:微染色体维持蛋白-2 (MCM-2)是比Ki-67更敏感的增殖标志物。本研究旨在评估MCM-2与Oncotype DX复发评分(ODX-RS)之间的关系，并根据TAILORx风险分类确定高危患者的MCM-2临界值。方法:选取激素受体(HR)阳性HER-2阴性的ODX-RS早期乳腺癌患者(pT1-2、pN0-N1、M0)为研究对象。根据TAILORx试验，将患者分为高危(ODX-RS≥26)和低危(ODX-RS)两组。结果:高危组MCM-2均值显著高于高危组[(60.2±11.2 vs 34.4±13.8,p < 0.001)]。在多因素分析中，MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003)和孕激素受体(PR)水平≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003)是提示高危人群的独立因素。MCM-2水平每增加一个单位，成为高危人群的可能性就增加1.27倍。在ROC曲线分析中，最佳MCM-2截止水平为50 (AUC: 0.921，敏感性:86.7%，特异性:96.0%，p < 0.001)。结论:我们的研究是文献中首次探讨hr阳性HER-2阴性早期乳腺癌患者ODX-RS与MCM-2水平之间的关系。在本研究中，根据TAILORx风险分类，MCM-2是识别高危患者的独立危险因素。对于不能进行Oncotype DX检测的患者，mcm2临界值(50)可能有助于决定是否进行辅助化疗。
MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification.
Background: The minichromosome maintenance protein-2 (MCM-2) is a more sensitive proliferation marker than Ki-67. This study aimed to evaluate the relationship between MCM-2 and Oncotype DX recurrence score (ODX-RS) and determine an MCM-2 cutoff value in high-risk patients according to TAILORx risk categorization.
Methods: Hormone receptor (HR) positive HER-2 negative early-stage breast cancer patients (pT1-2, pN0-N1, M0) who had ODX-RS were included in the study. According to the TAILORx trial, patients were divided into two groups with high (ODX-RS ≥26) and low risk (ODX-RS <26) in terms of ODX-RS. Formalin-fixed-paraffin-embedded tissues of patients were re-evaluated, and 3 µm sections were prepared for MCM-2 immuno-histochemical staining. The relationship between ODX-RS and the percentage of MCM-2 staining was evaluated in two groups. The ROC curve analysis was performed to determine the MCM-2 cut-off value for the TAILORx high-risk group (ODX-RS ≥26).
Results: The mean MCM-2 value was significantly higher in the high-risk group [(60.2 ± 11.2 vs 34.4 ± 13.8, p < 0.001)]. In the multivariate analysis, MCM-2 (OR: 1.27, 95% CI: 1.08-1.49, p = 0.003) and progesterone receptor (PR) levels ≤10% (OR: 60.9, 95% CI: 4.1-89.7, p = 0.003) were found to be independent factors indicating a high-risk group. A one-unit increase in MCM-2 level increased the likelihood of being in the high-risk group by 1.27 times. In the ROC curve analysis, the optimal MCM-2 cut-off level was 50 (AUC: 0.921, sensitivity: 86.7%, specificity: 96.0%, p < 0.001).
Conclusion: Our study is the first study in the literature to investigate the relationship between ODX-RS and MCM-2 levels in HR-positive HER-2 negative early breast-cancer patients. In this study, MCM-2 was an independent risk factor in identifying high-risk patients according to TAILORx risk classification. MCM 2 cut-off value (50) may help the decision on adjuvant chemotherapy in patients where the Oncotype DX test cannot be performed.
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