What does an elevated Cancer Antigen 15-3 (CA 15-3) level indicate in a female adult patient with a history of breast cancer?

What Does an Elevated CA 15-3 Indicate?

An elevated CA 15-3 most commonly indicates advanced or metastatic breast cancer, with the degree of elevation correlating with disease stage and burden—particularly when levels exceed 50 kU/L, which mandates an immediate search for metastases before finalizing treatment. 1, 2

Clinical Significance by Context

In Newly Diagnosed Breast Cancer

• CA 15-3 correlates with disease stage: Higher levels are observed in advanced cancer compared to localized disease, though it has poor sensitivity (only 16-31%) for early-stage disease 1, 2, 3
• When CA 15-3 exceeds 50 kU/L at presentation: Immediately perform metastatic workup before deciding on any treatment plan, as this threshold strongly suggests disseminated disease 1, 2
• Prognostic value: Pretreatment CA 15-3 is a recognized prognostic factor (though not proven independent), with levels >30.4 U/mL associated with worse outcomes independent of tumor size and nodal status 1, 4

During Active Treatment

• Persistently elevated CA 15-3 despite treatment: Indicates treatment failure and very poor prognosis 1, 5
• Rising CA 15-3 during therapy: Signals disease progression and should prompt consideration of therapy change, particularly in patients without readily measurable disease on imaging 2, 5
• Correlation with treatment response: CA 15-3 levels correlate with disease response during metastatic treatment, making it useful for monitoring alongside clinical examination 1

In Metastatic Disease Detection

• CA 15-3 is elevated in 62-86% of patients with metastatic breast cancer, with sensitivity varying by hormone receptor status 6, 3, 7
• Hormone receptor-positive tumors: CA 15-3 is elevated in 69% of HR+/HER2- cases at metastatic relapse, compared to only 41% in triple-negative cases 6
• Bone metastases: CA 15-3 shows particular utility for detecting osseous metastases, with 82% sensitivity when combined with bone scintigraphy 7
• Lead time: CA 15-3 can detect metastases 5-6 months before clinical symptoms appear 2, 3

Critical Limitations and Pitfalls

When NOT to Use CA 15-3

• Never use for screening or diagnosis: CA 15-3 has insufficient sensitivity (31% at presentation) and should not be ordered for these purposes 1, 2
• Do not use for routine surveillance after curative treatment: Despite early detection capability, this does not improve overall survival or quality of life 1, 2, 5
• Poor sensitivity for locoregional recurrence: CA 15-3 is unreliable for detecting local recurrence 1, 5

Essential Technical Requirements

• All measurements must be performed in the same laboratory using the same assay technique, as results vary significantly between methods 1, 2, 5
• Never use CA 15-3 as the sole criterion for treatment decisions: Always correlate with clinical examination and imaging findings 2, 5
• Do not routinely combine with other tumor markers: CA 15-3 remains the reference standard; adding multiple markers increases cost without improving decision-making 1, 2, 5

Appropriate Clinical Use

Monitoring Metastatic Disease

• Use CA 15-3 in conjunction with imaging, history, and physical examination to monitor treatment response in established metastatic breast cancer 2, 5
• In patients without measurable disease on imaging: Rising CA 15-3 can indicate treatment failure and prompt therapy change 2, 5
• Document baseline pretreatment CA 15-3 as the reference value for future comparison if metastatic recurrence is suspected 1, 5

Interpretation Thresholds

• Reference range: ≤30 U/mL (though some protocols use 25 U/mL or 36.7 U/mL depending on assay) 3, 7, 8
• High-risk threshold: >50 kU/L mandates immediate metastatic workup 1, 2
• Prognostic threshold: >30.4 U/mL associated with worse outcomes 4