Future oncology (London, England) · 2026
Personalized whole-genome-based ctDNA dynamics during neoadjuvant therapy across breast cancer subtypes: results from MONITOR-Breast.
СтатьяНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Foldi Julia, Hogan Gregory, Johansen Taber Katherine, LaBella Matthew, Sadler Britney, Patel Ravi, Balic Marija, Haslem Derrick, Mazo Canola Marcela, Peih-Ying Tsai Judy, Cusick Therese, Nathwani Niyati, Naito Yoichi, Funasaka Chikako, Wong Karlton, Ham Alexander, Acevedo Ashley, Battey C J, Gould Genevieve M, Muzzey Dale, Jasper Jeff
Аннотация
PURPOSE: Pathological complete response (pCR) after neoadjuvant therapy (NAT) strongly associates with reduced breast cancer relapse risk. Circulating tumor DNA (ctDNA) shows promise as a therapy-response biomarker, but prior studies had limited sampling and assay sensitivity. MONITOR-Breast characterized ctDNA dynamics across NAT at high temporal resolution using an ultrasensitive molecular residual disease (MRD) assay.
EXPERIMENTAL DESIGN: In this prospective observational study, 154 enrolled patients with breast cancer (all subtypes, Stages I-III) were tested at baseline, throughout NAT, and post-surgery using a whole genome sequencing-based MRD assay tracking up to 1,000 variants per patient.
RESULTS: Baseline ctDNA was detected in 93% of patients, with 20% detected in the ultrasensitive range (<100 parts per million). Post-NAT ctDNA positivity strongly associated with residual disease (RD) (odds ratio (OR)>20, p = 1 × 10-7) and post-operative positivity (OR =47, p = 1 × 10-6). All 56 patients with pCR and an evaluable sample had undetectable post-NAT ctDNA. Frequent testing revealed distinct patterns: 78% achieved rapid and/or sustained ctDNA clearance, while 22% exhibited persistent or intermittent positivity, and had significantly higher RD (OR =52, p = 3 × 10-9), and post-operative positivity (OR =25, p = 1 × 10-5).
CONCLUSIONS: Frequent, ultrasensitive ctDNA assessment provided comprehensive characterization of treatment response, revealing opportunities for de-escalation in early responders and escalation in those with persistent ctDNA.
EXPERIMENTAL DESIGN: In this prospective observational study, 154 enrolled patients with breast cancer (all subtypes, Stages I-III) were tested at baseline, throughout NAT, and post-surgery using a whole genome sequencing-based MRD assay tracking up to 1,000 variants per patient.
RESULTS: Baseline ctDNA was detected in 93% of patients, with 20% detected in the ultrasensitive range (<100 parts per million). Post-NAT ctDNA positivity strongly associated with residual disease (RD) (odds ratio (OR)>20, p = 1 × 10-7) and post-operative positivity (OR =47, p = 1 × 10-6). All 56 patients with pCR and an evaluable sample had undetectable post-NAT ctDNA. Frequent testing revealed distinct patterns: 78% achieved rapid and/or sustained ctDNA clearance, while 22% exhibited persistent or intermittent positivity, and had significantly higher RD (OR =52, p = 3 × 10-9), and post-operative positivity (OR =25, p = 1 × 10-5).
CONCLUSIONS: Frequent, ultrasensitive ctDNA assessment provided comprehensive characterization of treatment response, revealing opportunities for de-escalation in early responders and escalation in those with persistent ctDNA.