Abstract
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.
Highlights
The prognosis for patients with primary breast cancer is a function of disease extent at presentation and tumor biology
We have previously shown that tumor biology in older (>70 years) versus younger primary breast cancer cohorts can be distinguished by immunohistochemistry (IHC) using a panel of biomarkers, including ER, PR, HER2, Ki67, Bcl2, BRCA1, BRCA2, E-Cadherin, EGFR, LKB1, MDM2, MDM4, MUC1, p53, VEGF and cytokeratin markers of luminal and basal disease [4]
The findings suggest that clinical outcomes of older women with primary breast cancer can be predicted from the biology of their tumor using c-cyclin E alone
Summary
The prognosis for patients with primary breast cancer is a function of disease extent at presentation and tumor biology. Time-dependent factors, including metastatic involvement of draining axillary lymph nodes (stage) and the size of the primary tumor, indicate disease extent, while the degree of differentiation (grade) is used as a surrogate for biological aggressiveness. These histopathology-assessed features are classically combined into the Nottingham Prognostic Index (NPI) [1]. Tumors in older patients have distinct biological characteristics that are linked to favorable outcome, such as a higher proportion and degree of hormone receptor (estrogen receptor (ER) and/or progesterone receptor (PR)) positivity, and low histological grade and Ki67 proliferative index [4,5]. Biomarkers that may influence treatment strategy require interpretation in the specific clinical and biological context of older women
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
