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Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age

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 interpr...

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Autores principales: Johnston, Simon J., Syed, Binafsha M., Parks, Ruth M., Monteiro, Cíntia J., Caruso, Joseph A., Green, Andrew R., Ellis, Ian O., Hunt, Kelly K., Karakas, Cansu, Keyomarsi, Khandan, Cheung, Kwok-Leung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140020/
https://www.ncbi.nlm.nih.gov/pubmed/32197318
http://dx.doi.org/10.3390/cancers12030712
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author Johnston, Simon J.
Syed, Binafsha M.
Parks, Ruth M.
Monteiro, Cíntia J.
Caruso, Joseph A.
Green, Andrew R.
Ellis, Ian O.
Hunt, Kelly K.
Karakas, Cansu
Keyomarsi, Khandan
Cheung, Kwok-Leung
author_facet Johnston, Simon J.
Syed, Binafsha M.
Parks, Ruth M.
Monteiro, Cíntia J.
Caruso, Joseph A.
Green, Andrew R.
Ellis, Ian O.
Hunt, Kelly K.
Karakas, Cansu
Keyomarsi, Khandan
Cheung, Kwok-Leung
author_sort Johnston, Simon J.
collection PubMed
description 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.
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spelling pubmed-71400202020-04-13 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, Cíntia J. Caruso, Joseph A. Green, Andrew R. Ellis, Ian O. Hunt, Kelly K. Karakas, Cansu Keyomarsi, Khandan Cheung, Kwok-Leung Cancers (Basel) Article 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. MDPI 2020-03-18 /pmc/articles/PMC7140020/ /pubmed/32197318 http://dx.doi.org/10.3390/cancers12030712 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Johnston, Simon J.
Syed, Binafsha M.
Parks, Ruth M.
Monteiro, Cíntia J.
Caruso, Joseph A.
Green, Andrew R.
Ellis, Ian O.
Hunt, Kelly K.
Karakas, Cansu
Keyomarsi, Khandan
Cheung, Kwok-Leung
Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title_full Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title_fullStr Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title_full_unstemmed Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title_short Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age
title_sort cytoplasmic cyclin e is an independent marker of aggressive tumor biology and breast cancer-specific mortality in women over 70 years of age
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140020/
https://www.ncbi.nlm.nih.gov/pubmed/32197318
http://dx.doi.org/10.3390/cancers12030712
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