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Circulating tumour DNA dynamics during alternating chemotherapy and hormonal therapy in metastatic breast cancer: the ALERT study

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posted on 2024-05-02, 09:27 authored by Rebecca C Allsopp, Qi Guo, Karen Page, Shradha Bhagani, Anna Kasim, Philip Badman, Laura Kenny, Justin Stebbing, Jacqueline A Shaw

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 Biology

Version

  • VoR (Version of Record)

Published in

Breast Cancer Research and Treatment

Publisher

Springer Science and Business Media LLC

issn

0167-6806

eissn

1573-7217

Copyright date

2024

Available date

2024-05-02

Language

en

Deposited by

Dr Rebecca Allsopp

Deposit date

2024-04-29

Rights Retention Statement

  • No

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