Analysis of Circulating Tumor DNA (ctDNA) in Early-Stage Breast Cancer: A Report on Clinical Outcomes and Sustainable Development Goals

A real-world analysis utilizing the Flatiron Health Research Database establishes a significant correlation between positive circulating tumor DNA (ctDNA) and adverse clinical outcomes in patients with early-stage breast cancer. The findings, presented at the 2025 American Society of Clinical Oncology Annual Meeting, highlight the potential of ctDNA testing to advance Sustainable Development Goal 3 (Good Health and Well-being) by refining risk stratification and personalizing treatment, thereby contributing to the reduction of premature mortality from non-communicable diseases.

Study Design and Methodology

This retrospective, real-world cohort study was conducted to assess ctDNA testing trends and their association with clinical outcomes. The research aligns with SDG 17 (Partnerships for the Goals) by leveraging a large-scale, deidentified electronic health record–derived database from approximately 800 cancer care sites across the United States.

Cohort and Eligibility

• Patient Population: The study included patients diagnosed with stage I to III early-stage breast cancer on or after January 1, 2018.
• Inclusion Criteria:
  1. Documented hormone receptor and HER2 status.
  2. Record of at least one commercial ctDNA test in the early-stage setting.
  3. Age 18 years or older at diagnosis.
• Data Analysis: Unadjusted Kaplan-Meier methods were used to estimate Recurrence-Free Survival (RFS) and Overall Survival (OS). Multivariable Cox proportional hazards models were employed to assess the association between ctDNA positivity and RFS, adjusting for key demographic and clinical variables to support SDG 10 (Reduced Inequalities) by accounting for factors like age, race, and insurance status.

Key Findings and Impact on Health Outcomes (SDG 3)

The analysis of 4,639 patients revealed that 19.9% (921 patients) had at least one positive ctDNA test. These results are pivotal for achieving the targets of SDG 3, particularly in improving health outcomes and reducing mortality.

Overall Survival (OS) and Recurrence-Free Survival (RFS)

• Overall Survival: Patients with a positive ctDNA result demonstrated a 5-year OS probability of 85%, compared to 98% in ctDNA-negative patients. This stark difference underscores the prognostic value of ctDNA status.
• Recurrence-Free Survival: RFS was significantly lower in the ctDNA-positive cohort across all breast cancer subtypes. At the 3-year mark, adjusted hazard ratios (HR) indicated a substantially higher risk of recurrence for ctDNA-positive patients:
  • Hormone receptor–positive/HER2-negative: HR 10.7
  • Hormone receptor–negative/HER2-negative: HR 10.7
  • Hormone receptor–positive/HER2-positive: HR 11.8
  • Hormone receptor–negative/HER2-positive: HR 8.94

Testing Trends and Technological Adoption (SDG 9)

The study documents the increasing integration of scientific innovation into clinical practice, a core component of SDG 9 (Industry, Innovation, and Infrastructure).

• The adoption of ctDNA testing rose from 1.6% of eligible patients in 2020 to 4.25% in 2023.
• The median time from diagnosis to the first ctDNA test decreased from 35 months to 8 months for patients diagnosed since 2022, indicating more rapid integration of this technology.

Clinical Implications and Future Directions

The findings strongly suggest that ctDNA status is a powerful independent predictor of recurrence and survival in early-stage breast cancer. Integrating ctDNA testing into standard clinical practice can directly support the achievement of global health goals.

Opportunities for Clinical Integration

1. Refined Risk Stratification: Use ctDNA status to more accurately identify patients at high risk of recurrence, moving beyond traditional staging.
2. Personalized Treatment: Inform decisions regarding the escalation or de-escalation of therapy, ensuring patients who need intensified treatment receive it, which is central to the mission of SDG 3.

Study Limitations and Considerations for Equitable Access (SDG 10)

While promising, the study has limitations that must be addressed to ensure its benefits are realized equitably, in line with SDG 10 (Reduced Inequalities).

• Selection Bias: Findings may reflect trends among early adopters and may not be generalizable. Broader implementation requires careful monitoring to prevent disparities in access.
• Data Gaps: The clinical rationale for ordering tests was not captured, and the short follow-up period limited the ability to perform adjusted OS analyses.
• Future Research: Longer follow-up and prospective validation in clinical trials are necessary to confirm the prognostic value of ctDNA and ensure its application benefits all patient populations.

Reference

Fidyk E, Ward PJ, Estevez M, et al. Real-world (rw) ctDNA testing trends and associated outcomes in patients (pts) with early stage breast cancer (EBC). J Clin Oncol. 2025;43(suppl 16):555. doi:10.1200/jco.2025.43.16_suppl.555

Analysis of Sustainable Development Goals (SDGs) in the Article

SDGs Addressed or Connected to the Issues Highlighted

• SDG 3: Good Health and Well-being: The article’s primary focus is on improving health outcomes for patients with early-stage breast cancer. It discusses a new diagnostic method (ctDNA testing) to predict survival rates and recurrence risk, which is central to ensuring healthy lives and promoting well-being.
• SDG 9: Industry, Innovation, and Infrastructure: The article highlights scientific research and technological innovation within the healthcare sector. The study itself, using a large real-world database, and the increasing adoption of ctDNA testing technology in clinical practice are direct examples of enhancing scientific research and upgrading technological capabilities.

Specific Targets Identified

1. SDG 3: Good Health and Well-being

   • Target 3.4: “By 2030, reduce by one-third premature mortality from non-communicable diseases through prevention and treatment and promote mental health and well-being.”
     
     Explanation: Breast cancer is a non-communicable disease. The research discussed aims to improve treatment outcomes by identifying high-risk patients who could benefit from “escalated therapies.” This directly contributes to reducing premature mortality. The study’s focus on “overall survival (OS)” and “recurrence-free survival (RFS)” aligns perfectly with this target.
   • Target 3.d: “Strengthen the capacity of all countries, in particular developing countries, for early warning, risk reduction and management of national and global health risks.”
     
     Explanation: The article describes how ctDNA testing can be used to “refine risk stratification.” This technology serves as an advanced tool for early warning of cancer recurrence, enabling better management of health risks for patients.

2. SDG 9: Industry, Innovation, and Infrastructure

   • Target 9.5: “Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries…including…encouraging innovation.”
     
     Explanation: The study is a form of scientific research presented at a major clinical oncology meeting. It evaluates the clinical integration of an innovative technology (ctDNA testing). The article notes that “Trends over time indicated increased adoption of ctDNA testing in clinical practice,” which demonstrates the upgrading of technological capabilities in oncology care.

Indicators Mentioned or Implied

1. For SDG Target 3.4

   • Indicator 3.4.1: “Mortality rate attributed to…cancer…”
     
     Explanation: The article provides specific data related to cancer survival, which is the inverse of mortality. It states, “Patients with a ctDNA-positive result had a 5-year OS probability of 85%…compared with 98% in ctDNA-negative patients.” It also provides 3-year Recurrence-Free Survival (RFS) probabilities for different subgroups, which is a measure of treatment effectiveness and disease management.

2. For SDG Target 3.d

   • Implied Indicator: Adoption rate of advanced diagnostic technologies for risk management.
     
     Explanation: The article explicitly measures the uptake of ctDNA testing, stating it rose “from 1.6% of eligible patients in 2020 to 4.25% in 2023.” This serves as a direct indicator of the strengthening capacity for health risk management through new technology.

3. For SDG Target 9.5

   • Implied Indicator: Outputs of scientific research and integration of new technologies.
     
     Explanation: The study itself, published and presented at a scientific conference (“J Clin Oncol. 2025;43(suppl 16):555″), is an output of scientific research. Furthermore, the rising prevalence of ctDNA testing (“Testing prevalence was highest in the hormone receptor–negative/HER2-negative subgroup (4.9%)”) indicates the successful integration of this innovation into clinical practice.

Summary Table of Findings

Source: oncnursingnews.com