Beyond the Scan: What Imaging Cannot Tell Us
A patient completes surgery for breast cancer. Their imaging looks clear. Their oncologist is cautiously optimistic. But somewhere in their bloodstream, microscopic tumour cells may still be circulating: invisible to radiology, yet capable of driving future metastasis. This is the clinical reality of Minimal Cellular Residual Disease (MCRD), and it is one of the most pressing unsolved challenges in breast cancer management.
This study explores a powerful approach to detecting MCRD in breast cancer patients by measuring PD-L1 expression on Circulating Tumor Cells (CTCs) as a dynamic, real-time biomarker of immune evasion and metastatic risk.
Why PD-L1 on CTCs Matters
PD-L1 is well established as an immune checkpoint marker in tissue biopsies, its expression informing immunotherapy eligibility and predicting treatment response. But tissue-based PD-L1 assessment captures only a static snapshot of tumour biology at a single point in time.
CTCs, by contrast, are dynamic, shed continuously by the tumour into the bloodstream and reflective of the tumour’s real-time biological state.
When CTCs overexpress PD-L1, the implications are profound.
PD-L1-positive CTCs can deactivate immune T cells in circulation, effectively shielding themselves from immune elimination and enabling the cascade of micro-metastasis to proceed unchecked. Measuring PD-L1 expression on CTCs therefore offers a window into the tumour’s immune evasion strategy that tissue biopsy simply cannot provide.
Our Study: 1,294 Breast Cancer Patients
In a retrospective analysis of 1,294 breast cancer patients spanning early to late-stage disease, peripheral blood samples were analysed for CTC presence, CTC clusters, and PD-L1 expression using the CDSCO-approved OncoDiscover platform: processing just 1.5 mL of blood per patient. CTCs were confirmed using a rigorous four-marker protocol (EpCAM+ve, CK18+ve, DAPI+ve, CD45-ve) and PD-L1 expression was quantified using linear fluorescence intensity gradients on an automated Zeiss Microscope.
What We Found
The findings paint a clinically significant picture:
- 73.20% of patients (n=978) showed ≥1 CTCs at baseline; confirming the high prevalence of MCRD in breast cancer even when imaging appears clear
- Of those with detectable CTCs, a striking 87.69% (n=406/463) showed PD-L1 expression; revealing the majority of breast cancer CTCs are actively engaging in immune evasion
- The 41-50 age group showed the highest CTC burden (21.61%), while the 51–60 age group showed the highest rates of CTC clusters (29.08%) and PD-L1-positive CTCs (42.91%)
- 2.71% of patients showed CTC clusters: a finding associated with particularly aggressive metastatic potential
- Mean CTC count including clusters was 3.90, with mean PD-L1-positive CTCs at 3.40
The computational model demonstrated strong correlation between blood-based CTC outcomes and normal probability scores, validating its predictive utility.
Why This Matters
The high prevalence of PD-L1-positive CTCs across this cohort, even in patients without radiographic evidence of disease makes a compelling case for routine CTC-PD-L1 profiling in breast cancer management. Patients harbouring MCRD despite clear imaging represent a high-risk group that current surveillance strategies may be missing entirely.
Identifying these patients earlier and understanding the immune evasion mechanisms their tumour cells are employing, opens new opportunities for therapy escalation, immunotherapy selection, and more informed longitudinal monitoring. This is precision oncology working at its most clinically meaningful level.
Published at the ASCO Annual Meeting 2025 | DOI: 10.1200/JCO.2025.43.16_suppl.e15036
Presented by Sreeja Jayant, MS | Actorius Innovations and Research | Publication Only: Developmental Therapeutics — Molecularly Targeted Agents and Tumor Biology
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