A simple ctDNA blood test may soon revolutionize how we detect breast cancer recurrence — catching minimal residual disease (MRD) years before scans or symptoms appear. In this exclusive interview and slide companion from her MOASC presentation, UCLA oncologist Dr. Marla D. Lipsyc-Sharf shares powerful real-world data showing how ctDNA MRD surveillance in breast cancer is already changing management in over 80% of positive cases.
Watch the full video above as Dr. Lipsyc-Sharf answers the biggest questions oncologists and patients are asking about circulating tumor DNA testing today.
“Patients at high risk of recurrence years after diagnosis can have detectable ctDNA from months to up to three years — sometimes even longer — prior to metastatic recurrence.” — Dr. Marla D. Lipsyc-Sharf, MD
Why Current Breast Cancer Surveillance Falls Short
Standard guidelines still wait for symptoms before ordering imaging. Routine scans in the adjuvant setting are not recommended due to low yield, cost, radiation, and anxiety. Dr. Lipsyc-Sharf’s data shows many recurrences are caught too late.
What Is ctDNA and How Does It Detect MRD?
Cancer cells shed tiny fragments of DNA into the blood. Ultrasensitive assays like Signatera can detect these tumor-specific signals long before radiographic recurrence.
Key findings from the UCLA cohort:
- 100% of patients with detectable ctDNA eventually developed distant recurrence.
- Median lead time: 1.39 years (up to 4.24 years).
- Median overall survival from first positive ctDNA: 3.08 years.
“My hope is that we will see evidence of improved breast cancer outcomes or quality of life within the next five years, so ctDNA can become part of standard care.” — Dr. Marla D. Lipsyc-Sharf, MD
Real-World Impact: ctDNA Is Already Changing Practice
National Signatera data (N=7,984 adjuvant breast cancer patients):
- Management changed in >80% of positive ctDNA cases (earlier imaging, therapy switches, trials).
- Median time from positive ctDNA to distant recurrence: 13.3 months.
- Excellent negative predictive value across all subtypes: <2% recurrence risk in next 3–6 months if ctDNA-negative.
Subtype Differences Matter in ctDNA MRD Surveillance
Performance varies significantly by breast cancer subtype:
| Breast Cancer Subtype | Lead Time Advantage | ctDNA Levels | Key Clinical Note |
|---|---|---|---|
| ER+/HER2– | Longest (often years) | Lower | Needs ultrasensitive assay |
| Triple-Negative | Shorter | Higher | Faster intervention window |
| HER2+ | Intermediate | Higher | Strong negative predictive value |
Serial testing significantly boosts accuracy, especially years after diagnosis.
Can Treating ctDNA-Positive MRD Improve Outcomes?
Several practice-changing trials are now testing exactly that:
Highlighted Interventional Trials
- DARE Trial (NCT04567420) – Palbociclib + fulvestrant vs endocrine therapy in ctDNA+ HR+/HER2– patients.
- TRAK-ER (NCT04985266) – Palbociclib + fulvestrant randomization.
- MIRI Trial (TRIO B-14) – Dr. Lipsyc-Sharf’s IIT (NCT07191717): imlunestrant + abemaciclib in ctDNA+ patients (primary endpoint: ctDNA clearance).
- ZEST (NCT04915755) – Niraparib vs placebo in molecular relapse.
- Others: TREAT ctDNA, PREDICT-RD, ASPRIA, LEADER, CATE.
Full trial tables from the presentation are embedded below.
Precision Approach: Matching ctDNA Findings to Targeted Therapies
~50% of ctDNA-positive patients have actionable alterations (PIK3CA, ESR1, BRCA, etc.). The proposed algorithm includes PI3K/AKT inhibitors, oral SERDs, PARP inhibitors, or HER2 TKIs when appropriate.
Summary: The Future of ctDNA MRD Surveillance in Breast Cancer
- No standard test currently exists for distant recurrence surveillance.
- ctDNA is strongly prognostic and already drives real-world decisions.
- Subtype-specific strengths create opportunities for personalized strategies.
- Multiple trials will determine if early intervention on MRD improves survival and quality of life.
- The next 5 years could bring ctDNA into guidelines.
Call to Action Oncologists: Discuss ctDNA testing and trial enrollment with high-risk patients. Patients:
Watch the complete video interview with Dr. Marla Lipsyc-Sharf.
Related Content
References
Pusztai L et al. ASCO 2025: Circulating tumor (ct)DNA monitoring of ER+/HER2- high-risk breast cancer during adjuvant endocrine therapy (DARE trial update)
Lipsyc-Sharf M et al. J Clin Oncol 2022: Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor-Positive, HER2-Negative Breast Cancer
Lipsyc-Sharf M et al. ASCO 2025: Impact of circulating tumor DNA (ctDNA) surveillance on clinical care for patients with stage I-III breast cancer
Lipsyc-Sharf M et al. SABCS 2024: Actionable genomic alterations in ctDNA-positive early breast cancer (real-world data) (Poster PS9-01; full abstract available on SABCS platform)
Turner NC et al. Ann Oncol 2023: Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease
