Cytoplasmic cyclin E is an independent marker of aggressive tumor biology and breast cancer-specific mortality in women over 70 years of age

Johnston, Simon J; Syed, Binafsha M; Parks, Ruth M; Monteiro, C�ntia J; Caruso, Joseph A; Green, Andrew R; Ellis, Ian O; Hunt, Kelly K; Karakas, Cansu; Keyomarsi, Khandan; Cheung, Kwok Leung

Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox’s proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93–20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients.

Citation

Johnston, S. J., Syed, B. M., Parks, R. M., Monteiro, C. J., Caruso, J. A., Green, A. R., Ellis, I. O., Hunt, K. K., Karakas, C., Keyomarsi, K., & Cheung, K. L. (2020). Cytoplasmic cyclin E is an independent marker of aggressive tumor biology and breast cancer-specific mortality in women over 70 years of age. Cancers, 12(3), Article 712. https://doi.org/10.3390/cancers12030712

• Journal Article Type: Article
• Acceptance Date: Mar 15, 2020
• Online Publication Date: Mar 18, 2020
• Publication Date: Mar 18, 2020
• Deposit Date: Mar 19, 2020
• Publicly Available Date: Mar 19, 2020
• Journal: Cancers
• Electronic ISSN: 2072-6694
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Issue: 3
• Article Number: 712
• DOI: https://doi.org/10.3390/cancers12030712
• Keywords: breast cancer; cyclin E; older patients; biomarker; tumor biology; prognosis; survival
• Public URL: https://nottingham-repository.worktribe.com/output/4168781
• Publisher URL: https://www.mdpi.com/2072-6694/12/3/712