Is there concern for recurrence or metastasis in a breast cancer patient with slightly elevated CA 15-3 levels?

Evaluation of Slightly Elevated CA 15-3 Levels in Breast Cancer Follow-up

The slightly elevated CA 15-3 levels of 39 U/mL in 08/2023 and 36 U/mL in 08/2024 in a patient with history of left mastectomy, axillary lymph node dissection, and radiation do not warrant significant concern for recurrence, as these values are only marginally above the normal threshold and have remained stable over time.

Understanding CA 15-3 in Breast Cancer Monitoring

CA 15-3 is a breast-associated mucin that can be used as a tumor marker in breast cancer follow-up. According to current guidelines:

• The American Society of Clinical Oncology (ASCO) does not recommend CA 15-3 for routine surveillance after primary breast cancer therapy 1.
• CA 15-3 has limited sensitivity for detecting early recurrence, with studies showing it detects only about 36% of relapses 2.
• Present data are insufficient to recommend CA 15-3 alone for monitoring response to treatment 1.

Interpretation of Current CA 15-3 Values

The patient's CA 15-3 values require contextual interpretation:

• The normal reference range for CA 15-3 is typically ≤30 U/mL 3.
• The patient's values (39 U/mL and 36 U/mL) are only slightly elevated.
• Importantly, the values have remained stable or even slightly decreased over a one-year period.
• The stability of these values is reassuring, as progressive disease typically shows increasing marker levels.

Clinical Significance of Mildly Elevated CA 15-3

Several factors suggest these values are not highly concerning:

• Studies indicate that two consecutive rising values are more concerning than stable, mildly elevated values 3.
• An increase of ≥20% in CA 15-3 may indicate disease progression (sensitivity 77%) 3, which is not seen in this case.
• Mild elevations of CA 15-3 can occur in non-malignant conditions including chronic hepatitis, liver cirrhosis, sarcoidosis, tuberculosis, and systemic lupus erythematosus 4.

Recommended Approach

Given the current evidence, the following approach is recommended:

1. Continue regular clinical follow-up as these values alone do not warrant aggressive investigation.

2. Consider additional evaluation only if:

   • CA 15-3 shows a significant increase (≥20%) in subsequent measurements
   • New symptoms develop (bone pain, persistent cough, neurological symptoms)
   • Abnormal findings appear on physical examination

3. If further evaluation is needed:

   • Diagnostic imaging should be guided by symptoms (mammography, breast ultrasound, chest/abdominal/pelvic CT, bone scan if bone pain is present) 3.
   • PET/CT may be considered if other imaging is inconclusive 3.

Important Caveats

• CA 15-3 has limited sensitivity for detecting locoregional recurrence or contralateral breast cancer 2.
• Serial measurements should ideally be performed in the same laboratory using the same technique 3.
• Normal or slightly elevated CA 15-3 levels do not completely exclude metastatic disease, especially in early recurrence 3.
• Changes in CA 15-3 levels rather than absolute values may be more meaningful for individual patients 3.

Conclusion

The stable, mildly elevated CA 15-3 values in this post-mastectomy patient do not suggest disease recurrence or progression. Continue routine follow-up without additional testing unless there are new symptoms or a significant increase in marker levels.