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.