Breast Cancer: Targets and Therapy (Sep 2023)

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

  • Ünal Ç,
  • Özmen T,
  • İlgün AS,
  • Ordu Ç,
  • Özkurt E,
  • Ak N,
  • Alço G,
  • Erdoğan İyigün Z,
  • Kurt S,
  • Duymaz T,
  • Öztürk MA,
  • Elbüken Çelebi F,
  • Yararbaş K,
  • Soybir G,
  • Aktepe F,
  • Özmen V

Journal volume & issue
Vol. Volume 15
pp. 659 – 669

Abstract

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Çağlar Ünal,1 Tolga Özmen,2,3 Ahmet Serkan İlgün,4 Çetin Ordu,5 Enver Özkurt,6 Naziye Ak,7 Gül Alço,8 Zeynep Erdoğan İyigün,9 Sevgi Kurt,10 Tomris Duymaz,11 Mehmet Alper Öztürk,12 Filiz Elbüken Çelebi,13 Kanay Yararbaş,14 Gürsel Soybir,15 Fatma Aktepe,16 Vahit Özmen17 1Division of Medical Oncology, Department of Internal Medicine, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey; 2Division of Gastrointestinal and Oncologic Surgery, Harvard Medical School, Boston, MA, USA; 3Division of Gastrointestinal and Oncologic Surgery, Massachusetts General Hospital, Boston, MA, USA; 4Department of Surgery, Mater Dei Hospital, Msida, Malta; 5Division of Medical Oncology, Department of Internal Medicine, Gayrettepe Florence Nightingale Hospital, İstanbul, Turkey; 6Department of General Surgery, Istanbul Florence Nightingale Hospital, İstanbul, Turkey; 7Division of Medical Oncology, Department of Internal Medicine, Istanbul Florence Nightingale Hospital, İstanbul, Turkey; 8Department of Radiation Oncology, Gayrettepe Florence Nightingale Hospital, İstanbul, Turkey; 9Department of Physical Therapy and Rehabilitation, Göztepe Medical Park Hospital, İstanbul, Turkey; 10Department of Plastic Surgery, Istanbul Florence Nightingale Hospital, İstanbul, Turkey; 11Department of Physiotherapy and Rehabilitation, Faculty of Health Sciences, Istanbul Bilgi University, Istanbul, Turkey; 12Department of General Surgery, Biruni Hospital, İstanbul, Turkey; 13Department of Radiology, Yeditepe University Hospital, İstanbul, Turkey; 14Department of Medical Genetics, Demiroglu Bilim University, Istanbul, Turkey; 15Department of General Surgery, Memorial Şişli Hospital, İstanbul, Turkey; 16Department of Pathology, Memorial Şişli Hospital, İstanbul, Turkey; 17Department of General Surgery, Istanbul University Istanbul School of Medicine, İstanbul, TurkeyCorrespondence: Çağlar Ünal, Division of Medical Oncology, Department of Internal Medicine, Kartal Dr. Lütfi Kırdar City Hospital, İstanbul, Turkey, Email [email protected]: 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: breast cancer, MCM-2, Oncotype DX recurrence score, TAILORx risk categorization

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