MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification

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

MCM-2 Levels as a Potential Biomarker for Predicting High-Risk Breast Cancer Patients According to TAILORx Classification

Breast Cancer (Dove Med Press). 2023 Sep 1:15:659-669. doi: 10.2147/BCTT.S421535. eCollection 2023.

Authors

Çağlar Ünal¹, Tolga Özmen^{2

3}, Ahmet Serkan İlgün⁴, Çetin Ordu⁵, Enver Özkurt⁶, Naziye Ak⁷, Gül Alço⁸, Zeynep Erdoğan İyigün⁹, Sevgi Kurt¹⁰, Tomris Duymaz¹¹, Mehmet Alper Öztürk¹², Filiz Elbüken Çelebi¹³, Kanay Yararbaş¹⁴, Gürsel Soybir¹⁵, Fatma Aktepe¹⁶, Vahit Özmen¹⁷

Affiliations

¹ Division of Medical Oncology, Department of Internal Medicine, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey.
² Division of Gastrointestinal and Oncologic Surgery, Harvard Medical School, Boston, MA, USA.
³ Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA, USA.
⁴ Department of Surgery, Mater Dei Hospital, Msida, Malta.
⁵ Division of Medical Oncology, Department of Internal Medicine, Gayrettepe Florence Nightingale Hospital, İstanbul, Turkey.
⁶ Department of General Surgery, Istanbul Florence Nightingale Hospital, İstanbul, Turkey.
⁷ Division of Medical Oncology, Department of Internal Medicine, Istanbul Florence Nightingale Hospital, İstanbul, Turkey.
⁸ Department of Radiation Oncology, Gayrettepe Florence Nightingale Hospital, İstanbul, Turkey.
⁹ Department of Physical Therapy and Rehabilitation, Göztepe Medical Park Hospital, İstanbul, Turkey.
¹⁰ Department of Plastic Surgery, Istanbul Florence Nightingale Hospital, İstanbul, Turkey.
¹¹ Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul Bilgi University, Istanbul, Turkey.
¹² Department of General Surgery, Biruni Hospital, İstanbul, Turkey.
¹³ Department of Radiology, Yeditepe University Hospital, İstanbul, Turkey.
¹⁴ Department of Medical Genetics, Demiroglu Bilim University, Istanbul, Turkey.
¹⁵ Department of General Surgery, Memorial Şişli Hospital, İstanbul, Turkey.
¹⁶ Department of Pathology, Memorial Şişli Hospital, İstanbul, Turkey.
¹⁷ Department of General Surgery, Istanbul University Istanbul School of Medicine, İstanbul, Turkey.

Abstract

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.

Keywords: MCM-2; Oncotype DX recurrence score; TAILORx risk categorization; breast cancer.

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.