Ünal Çağlar, Özmen Tolga, İlgün Ahmet Serkan, Ordu Çetin, Özkurt Enver, Ak Naziye, Alço Gül, Erdoğan İyigün Zeynep, Kurt Sevgi, Duymaz Tomris, Öztürk Mehmet Alper, Elbüken Çelebi Filiz, Yararbaş Kanay, Soybir Gürsel, Aktepe Fatma, Özmen Vahit
Division of Medical Oncology, Department of Internal Medicine, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey.
Division of Gastrointestinal and Oncologic Surgery, Harvard Medical School, Boston, MA, USA.
Breast Cancer (Dove Med Press). 2023 Sep 1;15:659-669. doi: 10.2147/BCTT.S421535. eCollection 2023.
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.
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).
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).
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.
微小染色体维持蛋白2（MCM-2）是一种比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。
纳入接受了ODX-RS检测的激素受体（HR）阳性、人表皮生长因子受体2（HER-2）阴性的早期乳腺癌患者（pT1-2，pN0-N1，M0）。根据TAILORx试验，按照ODX-RS将患者分为高危（ODX-RS≥26）和低危（ODX-RS＜26）两组。对患者的福尔马林固定石蜡包埋组织进行重新评估，并制备3μm切片用于MCM-2免疫组织化学染色。评估两组中ODX-RS与MCM-2染色百分比之间的关系。进行ROC曲线分析以确定TAILORx高危组（ODX-RS≥26）的MCM-2临界值。
高危组的MCM-2平均水平显著更高[（60.2±11.2 vs 34.4±13.8，p＜0.001）]。在多因素分析中，MCM-2（比值比：1.27，95%置信区间：1.08-1.49，p = 0.003）和孕激素受体（PR）水平≤10%（比值比：60.9，95%置信区间：4.1-89.7，p = 0.003）被发现是指示高危组的独立因素。MCM-2水平每增加一个单位，处于高危组的可能性增加1.27倍。在ROC曲线分析中，最佳MCM-2临界水平为50（曲线下面积：0.921，灵敏度：86.7%，特异性：96.0%，p＜0.001）。
我们的研究是文献中首次调查HR阳性、HER-2阴性早期乳腺癌患者中ODX-RS与MCM-2水平之间关系的研究。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。MCM-2临界值（50）可能有助于无法进行Oncotype DX检测的患者辅助化疗决策。
