Anglia Ruskin Research Online (ARRO)
Browse

Serial Postoperative Circulating Tumor DNA Assessment Has Strong Prognostic Value During Long-Term Follow-Up in Patients With Breast Cancer

Download (1.06 MB)
journal contribution
posted on 2024-06-24, 09:45 authored by Jacqueline A Shaw, Karen Page, Evie Wren, Elza C de Bruin, Ekaterina Kalashnikova, Robert Hastings, Rob McEwen, Eddie Zhang, Marc Wadsley, Emmanuel Acheampong, Derrick Renner, Kelly LT Gleason, Bana Ambasager, Daniel Stetson, Daniel Fernandez-Garcia, David Guttery, Rebecca C Allsopp, Angel Rodriguez, Bernhard Zimmermann, Himanshu Sethi, Alexey Aleshin, Minetta C Liu, Cathy Richards, Justin Stebbing, Simak Ali, Farah Rehman, Susan Cleator, Laura Kenny, Samreen Ahmed, Anne C Armstrong, R Charles Coombes

PURPOSE Here, we report the sensitivity of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay (Signatera) for detection of molecular relapse during long-term follow-up of patients with breast cancer. METHODS A total of 156 patients with primary breast cancer were monitored clinically for up to 12 years after surgery and adjuvant chemotherapy. Semiannual blood samples were prospectively collected, and analyzed retrospectively to detect residual disease by ultradeep sequencing using ctDNA assays, developed from primary tumor whole-exome sequencing data. RESULTS Personalized Signatera assays detected ctDNA ahead of clinical or radiologic relapse in 30 of the 34 patients who relapsed (patient-level sensitivity of 88.2%). Relapse was predicted with a lead interval of up to 38 months (median, 10.5 months; range, 0-38 months), and ctDNA positivity was associated with shorter relapse-free survival ( P < .0001) and overall survival ( P < .0001). All relapsing triple-negative patients (n = 7/23) had a ctDNA-positive test within a median of 8 months (range, 0-19 months), while the 16 nonrelapsed patients with triple-negative breast cancer remained ctDNA-negative during a median follow-up of 58 months (range, 8-99 months). The four patients who had negative tests before relapse all had hormone receptor–positive (HR+) disease and conversely, five of the 122 nonrelapsed patients (all HR+) had an occasional positive test. CONCLUSION Serial postoperative ctDNA assessment has strong prognostic value, provides a potential window for earlier therapeutic intervention, and may enable more effective monitoring than current clinical tests such as cancer antigen 15-3. Our study provides evidence that those with serially negative ctDNA tests have superior clinical outcomes, providing reassurance to patients with breast cancer. For select cases with HR+ disease, decisions about treatment management might require serial monitoring despite the ctDNA-positive result.

History

Refereed

  • Yes

Volume

8

Issue number

8

Page range

e2300456

Publication title

JCO Precision Oncology

ISSN

2473-4284

Publisher

American Society of Clinical Oncology (ASCO)

Location

United States

File version

  • Published version

Language

  • eng

Item sub-type

Research Support, Non-U.S. Gov't, Journal Article

Media of output

Print

Affiliated with

  • School of Life Sciences Outputs