Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study
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 oestrogen 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).
Funding
Cancer Research UK to JAS and RCC (C14315/A23464)
History
Author affiliation
College of Life Sciences/Genetics & Genome BiologyVersion
- VoR (Version of Record)
Published in
Breast Cancer Research and TreatmentPublisher
Springer Science and Business Media LLCissn
0167-6806eissn
1573-7217Copyright date
2024Available date
2024-05-02Publisher DOI
Language
enPublisher version
Deposited by
Dr Rebecca AllsoppDeposit date
2024-04-29Rights Retention Statement
- No