Cell cycle traverse rate predicts long-term outcomes in a multi-institutional cohort of patients with triple-negative breast cancer

• Published in: BJC reports 2024-11, Vol.2 (1), p.87-10, Article 87
• Main Authors: Bhattarai, Shristi, Rupji, Manali, Chao, Hsueh-ping, Xu, Qi, Saini, Geetanjali, Rida, Padmashree, Aleskandarany, Mohammed A., Green, Andrew R., Ellis, Ian O., Janssen, Emiel A., Jonsdottir, Kristin, Rakha, Emad, Kowalski, Jeanne, Aneja, Ritu
• Format: Article
• Language: English
• Subjects: Biomedical and Life Sciences; Biomedicine; Cancer Research; Oncology
• ISSN: 2731-9377; 2731-9377
• DOI: 10.1038/s44276-024-00097-z

Background Ki67 index (KI) and mitotic index (MI) are proliferation markers with established prognostic value in breast carcinomas. While KI is evaluated immunohistochemically and reported as a percentage, MI is determined visually and reflects total mitotic cells in 10 high-power fields. Our objective was to integrate KI and MI into a novel metric; the cell cycle traverse rate (CCTR). Given the lack of prognostic and predictive biomarkers in TNBC, we sought to assess the potential of CCTR as a risk-stratification tool for chemotherapy-treated TNBC patients from two independent cohorts: the Nottingham group ( n  = 124) and the Norway group ( n  = 71). Methods We evaluated the ability of CCTR to predict survival after adjuvant chemotherapy for TNBC patients ( n  = 195) in two independent cohorts. Using immunohistochemistry and RNA sequencing, we determined the differences in immunohistochemical biomarkers, gene ontologies, molecular pathways and immune cell fractions based on CCTR. Results TNBC shows a significantly lower median CCTR compared to luminal A ( p