Affiliation:
1. University of Leicester
2. Imperial College London
3. Anglia Ruskin University
Abstract
Abstract
Purpose
Although changes in circulating tumour DNA (ctDNA) in breast cancer are well described, the kinetics of their fluctuations has not been described over short timescales. We investigated ctDNA dynamics during alternating cycles of chemotherapy and hormonal treatment in pre-treated patients with estrogen receptor positive metastatic breast cancer.
Methods
Patients received alternating, 9-week cycles of eribulin and aromatase inhibitors (AIs). The clinical primary endpoint, progression free survival (PFS) was monitored at 3, 6 and 9 months; secondary endpoints clinical benefit rate (CBR), safety and tolerability profiles were also assessed. Importantly, ctDNA fluctuations were monitored using the Oncomine™ Breast cfDNA assay to test whether biomarkers may change rapidly between chemotherapy and aromatase inhibitor (AI) treatment in the setting of advanced breast cancer, potentially reflecting disease dynamics.
Results
The median PFS was 202 days (95% CI: 135-undefined) and 235 days (95% CI: 235-undefined) at 6 and 9 months respectively, with a 50% CBR at both 6 and 9 months. Dynamic changes in ctDNA were observed in short timescales between chemotherapy and AI treatment and support the clinical benefit (CB) seen in individual patients and critically, appear informative of acquired resistance in real-time.
Conclusion
Changes in ctDNA can occur rapidly and reflect changes in patients’ clinical tumour responses (NCT02681523).
Publisher
Research Square Platform LLC