What is the recommended course of action if Carcinoembryonic Antigen (CEA) and Cancer Antigen 27.29 (CA 27.29) levels are normal?

Normal CA 27.29 and CEA: Clinical Interpretation and Management

When both CA 27.29 and CEA are normal in breast cancer patients, these markers should not be used for routine surveillance after primary treatment, and normal values do not exclude the presence of metastatic disease. 1

Key Clinical Implications of Normal Markers

Limited Sensitivity in Early Disease

• Normal CA 27.29 and CEA levels do not rule out breast cancer recurrence or metastatic disease. 1
• CA 27.29 has only 57.7% sensitivity for detecting recurrence, meaning 42% of recurrences will be missed despite normal marker levels 1
• In non-metastatic breast cancer, CA 15-3 (similar to CA 27.29) has only 33% sensitivity, while CEA is elevated in just 50-60% of metastatic cases 2
• Low marker levels do not exclude metastases and cannot be used to determine stage of disease 1

Appropriate Use of These Markers

For Post-Primary Treatment Surveillance:

• Do not use CA 27.29 or CEA for routine surveillance after primary breast cancer therapy, even if previously elevated markers have normalized. 1
• The American Society of Clinical Oncology explicitly recommends against routine surveillance with these markers because there is no demonstrated impact on survival, quality of life, or cost-effectiveness 1
• Although CA 27.29 can detect recurrence an average of 5.3 months earlier than clinical symptoms, this lead time does not change treatment options or improve outcomes 1

For Metastatic Disease Monitoring:

• Normal markers should only be monitored in patients with confirmed metastatic breast cancer during active therapy, and always in combination with imaging and clinical examination—never as standalone tests. 3, 2
• In metastatic disease, CA 27.29 is elevated in only 81% of cases, meaning 19% will have normal levels despite active disease 1, 3
• CEA adds minimal value, providing only 2.1% additional sensitivity when combined with CA 15-3/CA 27.29 2

Clinical Decision Algorithm

If Markers Are Normal After Primary Treatment:

1. Discontinue routine marker monitoring 1
2. Rely on clinical examination and symptom-directed imaging for surveillance 1
3. Do not use normal marker values to provide false reassurance—clinical vigilance remains essential 1, 2

If Markers Are Normal During Metastatic Disease Treatment:

1. Continue monitoring markers every 1-3 months only if they were initially elevated 4, 3
2. Base treatment decisions on imaging and clinical assessment, not marker levels alone 3, 2
3. A rising marker (≥20% increase for CA 27.29 or two values above baseline for CEA) suggests treatment failure, but normal or stable markers do not confirm treatment success 4, 3

Critical Pitfalls to Avoid

Common Clinical Errors:

• Many clinicians incorrectly order these tests for post-surgical follow-up—this is not evidence-based and leads to overdiagnosis without survival benefit 2
• Never initiate or change therapy based on marker levels alone without radiographic or pathologic confirmation of disease 4
• Do not interpret markers during the first 4-6 weeks of new therapy, as spurious early rises can occur even with effective treatment 4, 3

False Reassurance:

• Normal markers provide a false sense of security given their poor sensitivity 1, 2
• Up to 43% of recurrences occur with normal CA 27.29 levels 1
• In early-stage disease, sensitivity drops to as low as 6.4% for CA 27.29 and 4.5% for CEA 5

Special Considerations

When Normal Markers May Be Misleading:

• Benign conditions (pulmonary fibrosis, liver disease, inflammatory bowel disease) can cause false elevations, but normal values in these conditions do not exclude cancer 4, 6, 7
• In one case series, patients with pulmonary fibrosis had persistently elevated CA 27.29 that normalized after lung transplantation, despite no cancer recurrence 6, 7

Prognostic Context:

• Pre-treatment marker levels correlate with stage but are not independent prognostic factors 2
• Normal post-treatment markers do not modify prognosis or treatment planning 1