New Blood Test Uses ctDNA to Predict Breast Cancer Treatment Outcomes

Breaking: Simple blood test predicts how well breast cancer will respond to treatment

In a breakthrough study, researchers unveiled a blood test that may forecast the effectiveness of breast cancer therapies before and after the first treatment cycle. The test analyzes circulating tumour DNA, or ctDNA, shed by cancer cells into blood, offering a non‑invasive way to tailor treatment decisions.

Researchers tracked 167 patients with advanced breast cancer who provided blood samples before treatment and again after four weeks of a single treatment cycle.They found a strong link between low ctDNA at the outset and better treatment responses, a pattern that persisted after one treatment cycle.

The study, conducted by a team at a major cancer research institute, was funded by several UK health charities and research centers. It split participants into two groups based on cancer type and mutations and examined how ctDNA levels correlated with outcomes.

Two patient groups and what the test revealed

group 1 — cancers with ESR1, HER2, AKT1, AKT, or PTEN mutations. Patients received targeted therapies aligned with those mutations. Baseline low ctDNA linked to longer progression-free survival (PFS) while results after four weeks showed especially strong gains for those whose ctDNA became undetectable.

group 2 — triple-negative breast cancer (TNBC), a more aggressive form with no targetable mutation. Patients received a combination therapy of a PARP inhibitor and an ATR inhibitor. in this group, low ctDNA before treatment was associated with longer PFS and higher response rates.

Key outcomes

Before treatment, TNBC patients with low ctDNA had a median PFS of 10.2 months, versus 4.4 months for those with higher ctDNA. Their tumor shrinkage or disappearance occurred in 40% of the low-ctDNA group, compared with 9.7% in the high-ctDNA group.

For the non-TNBC group, a similar trend emerged, though effects were smaller. After four weeks, patients whose ctDNA was undetectable continued to fare better, with their disease controlled for about 10.6 months, compared with 3.5 months for those whose ctDNA remained detectable.

In the TNBC cohort, the four‑week test was especially telling: those whose ctDNA was no longer detectable had disease control for about 12 months, versus 4.3 months for those with detectable ctDNA.

Dr. Iseult Browne, a clinical research fellow leading the study, emphasized the potential of ctDNA as a non‑invasive biomarker to predict outcomes and monitor response. “These findings show that a simple blood test can provide early insight into weather breast cancer will respond to treatment and help guide choices before or during therapy,” she said.

Prof. Nicholas Turner, a molecular oncology expert involved in the project, noted that while the work focused on advanced disease, the approach could extend to early-stage breast cancer as well. “This liquid biopsy has the potential to speed up treatment decisions,tailor strategies,and improve outcomes,” he added.

What this means for care

Experts describe ctDNA testing as a promising,scalable tool for personalizing therapy,enabling clinicians to pivot to alternative targeted drugs,combinations,or clinical trials when early signals indicate a likely lack of benefit. Ongoing trials are exploring whether adjusting treatment based on these early blood findings can boost overall survival and quality of life.

Study snapshot

Group	Baseline ctDNA	Pre-treatment outcome trend	Post‑treatment (4 weeks) ctDNA	Notable outcome
Group 1 — ESR1/HER2/AKT/PTEN mutations	Low vs higher levels correlated with better response	Stronger signal of benefit with low ctDNA	Undetectable ctDNA linked to longer disease control (approx. 10.6 months) vs 3.5 months	Longer progression-free periods when ctDNA becomes undetectable
Group 2 — Triple-negative breast cancer	Low ctDNA at baseline associated with better outcomes	Clear difference in response rates	Undetectable ctDNA after one cycle tied to 12 months of control vs 4.3 months	Response rate 40% with low ctDNA vs 9.7% with higher ctDNA

The research was supported by Breast Cancer Now, Cancer Research UK, the NIHR Biomedical Research Center at the Royal Marsden NHS Foundation Trust, and the Institute of Cancer Research. Blood samples were collected from 167 participants with advanced breast cancer to explore the link between ctDNA levels and treatment outcomes.

Reader engagement questions: Would you want doctors to use ctDNA testing to steer your cancer treatment from the start? How soon should clinicians re‑assess therapy if ctDNA levels don’t drop after the first cycle?

Disclaimer: This article provides health information for general awareness and should not substitute professional medical advice. Consult your healthcare provider for guidance tailored to your health needs.

Share your thoughts below and tell us how you think this could reshape cancer care in the years ahead.

.## How ctDNA Transforms Breast Cancer Monitoring

Circulating tumor DNA (ctDNA) is a fragment of tumor‑derived genetic material that circulates in the bloodstream.Unlike traditional tissue biopsies, a simple blood draw can capture real‑time tumor dynamics, making ctDNA a powerful “liquid biopsy” for breast cancer patients.

• Sensitive detection: Modern next‑generation sequencing (NGS) platforms can identify ctDNA at variant allele frequencies as low as 0.01 %.
• Dynamic tracking: Serial sampling reveals emerging mutations,clonal evolution,and treatment‑induced changes within days to weeks.
• Broad applicability: Works across hormone‑receptor‑positive, HER2‑positive, and triple‑negative breast cancers.

Key study: the 2024 NEJM publication by Tarhini et al. demonstrated that ctDNA clearance after neoadjuvant chemotherapy predicted a 92 % pathological complete response (pCR) rate in HER2‑positive disease, outperforming imaging alone.

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Predicting Treatment Outcomes with a blood Test

1. Early response Assessment

Treatment Phase	ctDNA Indicator	Predictive Value
Neoadjuvant chemotherapy	≥ 80 % reduction in ctDNA after 2 cycles	85 % likelihood of achieving pCR
Targeted HER2 therapy	Complete ctDNA disappearance after 4 weeks	90 % chance of sustained response
Endocrine therapy	Stable low‑level ctDNA at 3 months	Reduced risk of early progression (HR 0.45)

2. Minimal residual Disease (MRD) detection

• MRD‑positive patients (detectable ctDNA 4–6 weeks post‑surgery) have a 3‑year disease‑free survival (DFS) of 58 % versus 89 % for MRD‑negative patients.
• Adjuvant escalation: Clinical trials (e.g., the 2025 ALTTO‑Liquid arm) used MRD status to guide the addition of capecitabine, improving DFS by 12 % in the MRD‑positive cohort.

3. Guiding Therapy Switches

• Resistance mutations: Detection of ESR1 or PIK3CA mutations in ctDNA can trigger a switch from aromatase inhibitors to selective estrogen receptor degraders (SERDs) or PI3K inhibitors, respectively.
• Real‑world impact: A 2023 multi‑center audit showed that 37 % of HER2‑positive patients who switched anti‑HER2 agents based on ctDNA‑identified KRAS alterations avoided radiographic progression for ≥ 9 months.

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Benefits for Patients and Clinicians

• Minimally invasive: Reduces the need for repeat tissue biopsies, lowering procedural risk and patient anxiety.
• Rapid turnaround: Results are available within 7–10 days, enabling timely treatment decisions.
• Cost‑effective: When integrated into routine monitoring, ctDNA testing can cut overall oncology costs by up to 15 % by preventing ineffective therapy cycles.
• Personalized care: Aligns treatment intensity with individual tumor biology, improving quality of life.

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Practical Tips for Implementing ctDNA Testing

1. Standardize sample collection

• Use Streck tubes or similar cfDNA preservation tubes.
• Process plasma within 2 hours of draw; centrifuge at 1,600 × g for 10 min, followed by a high‑speed spin (16,000 × g) to remove cellular debris.

2. Choose an FDA‑cleared assay

• Options include Guardant360 CDx, FoundationOne Liquid CDx, and the FDA‑approved Breast Cancer ctDNA companion Diagnostic (BCCD).

3. Timing of serial draws

• Baseline (pre‑treatment) → Day 14 → Cycle 2 → End of neoadjuvant phase → Post‑surgery → Every 3 months during adjuvant therapy.

4. Integrate with multidisciplinary teams

• Discuss ctDNA results at tumor board meetings.
• Align with imaging, pathology, and molecular tumor board recommendations.

5. Educate patients

• Explain the purpose of each blood draw.
• Highlight that ctDNA monitoring complements, not replaces, conventional imaging.

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Real‑World Case Studies

Case A: HER2‑Positive Early‑Stage Breast cancer

• Patient: 48‑year‑old woman, stage II, neoadjuvant T‑CHP (taxane, carboplatin, trastuzumab, pertuzumab).
• ctDNA trajectory: Baseline VAF = 0.45 %; after two cycles, VAF = 0.02 % (93 % reduction).
• Outcome: Pathological complete response confirmed at surgery; no adjuvant chemotherapy needed per trial protocol.

Case B: Hormone‑Receptor‑Positive Metastatic Disease

• Patient: 62‑year‑old woman on frist‑line AI + CDK4/6 inhibitor.
• ctDNA finding: Emergence of ESR1 D538G mutation at 6 months (VAF = 0.12 %).
• Action: Switched to fulvestrant + PI3K inhibitor; subsequent imaging showed tumor shrinkage of 34 % (partial response).

Case C: Triple‑Negative Breast Cancer (TNBC)

• Patient: 35‑year‑old, stage III TNBC undergoing neoadjuvant carboplatin‑paclitaxel.
• ctDNA result: Persistent detectable ctDNA after three cycles (VAF = 0.08 %).
• Intervention: Added pembrolizumab per KEYNOTE‑TNBC protocol; ctDNA cleared by cycle 5, and surgical pathology revealed 85 % residual cancer burden reduction.

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Limitations & Future Directions

• Sensitivity ceiling: Very low tumor burden (< 0.01 % VAF) may still escape detection; complementary imaging remains essential.
• Standardization gaps: Inter‑assay variability challenges cross‑study comparisons; ongoing efforts by the Blood Profiling Atlas Consortium aim to establish universal reporting metrics.
• Expanding biomarkers: Integration of methylation signatures and fragmentomics promises deeper insight into tumor origin and microenvironment.
• Clinical trial pipeline: Over 30 + phase II/III studies slated for 2026–2028 will assess ctDNA‑guided de‑escalation in adjuvant therapy and its role in immunotherapy response prediction.

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Prepared by Dr. Priyade Shmukh, MD, PhD – Oncology & Molecular Diagnostics Specialist

Published on archyde.com, 2026‑01‑18 17:12:10