Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Dual-Strategy ctDNA MRD Assessment Improves Detection Sensitivity Across Diverse Early Breast Cancer Cohorts (145329)

Darshana Patil 1 , Vineet Datta 1 , Dadasaheb Akolkar 1 , Rajan Datar 1 , Stefan Schuster 2 , Joachim Fluhrer 3 4 , Carol Haddad 5
  1. Datar Cancer Genetics, Nasik, MH, India
  2. Datar Cancer Genetics , Europe GmbH
  3. Genostics Australia PtyLtd, Avalon Beach, NSW, Australia
  4. Clinical Research, Genostics Australia, Sydney, NSW, Australia
  5. Private Practice, DrHaddad, Sydney, NSW, Australia

Background 
Detecting ctDNA-based MRD in early BC faces challenges like tumor diversity, clonal changes, and limits of current methods. Each approach, tumor-informed (TI) and tumor-agnostic (TA), has specific vulnerabilities that reduce the single-strategy-sensitivity. We evaluated a combined TI/TA platform that could improve MRD detection across a broader breast cancer cohort.

Methods
We analyzed 132 MRD assessments (median age 53, range 31-87) in patients with breast cancer after curative therapy. A combinatorial approach of TI ddPCR and TA NGS ctDNA methods, with CHIP filtering to improve analytical robustness. Detection by either approach rendered the sample MRD-positive. A sub-cohort of 74 patients with contemporaneous imaging data was analyzed for MRD–imaging concordance.

Results
Out of 132 assessments, 63 (47.7%) were MRD-positive, of which, 46.0% were detected by TI alone, 23.8% by TA alone, and 30.2% by both. Reliance on a single strategy would have missed 69.8% (44/63) of MRD-positive cases, demonstrating improved detection with the combined approach.

In sub-cohort with available clinicopathological data, MRD-positivity was observed across histological types: IDC (47.4%), ILC (41.7%); and receptor types: HR+/HER2− (46.8%), TNBC (47.1%), and HER2+ (40.0%).

In imaging subgroup (n=74), 94.6% (70/74) were imaging-negative at ctDNA assessment. MRD was detected in 31.1% (23/74) overall, including 27.1% (19/70) of imaging-negative patients, indicating occult molecular disease. All imaging-positive cases (4/4) were MRD-positive, with no discordance. At follow-up (median 113.5 days), MRD persisted in 23 patients; among those with imaging-confirmed recurrence (n=4), median lead time from MRD detection to radiologic progression was 9.75 months.

Conclusions
The hybrid TI/TA ctDNA MRD platform significantly outperforms either method; it identifies molecular residual disease across different biological types beyond conventional imaging. The complementary strengths of TI and TA approaches augments the sensitivity of MRD detection. These results support the use of hybrid MRD testing in post-treatment monitoring, early risk assessment, and MRD-guided clinical trials.