Prognostic Impact of Elevation of Cancer Antigen 15-3 (CA15-3) in Patients With Early Breast Cancer With Normal Serum CA15-3 Level

Jai Min Ryu ^# 1, Danbee Kang ^# 2 3, Juhee Cho ^2 3 4, Jeong Eon Lee ¹, Seok Won Kim ¹, Seok Jin Nam ¹, Se Kyung Lee ¹, Yeon Jin Kim ¹, Young-Hyuck Im ⁵, Jin Seok Ahn ⁵, Yeon Hee Park ⁵, Ji-Yeon Kim ⁵, Hyunjong Lee ⁶, Mira Kang ^7 8 9, Jong Han Yu ¹⁰

Affiliations expand

• PMID: 37051649
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• PMCID: PMC10139845
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• DOI: 10.4048/jbc.2023.26.e17

Free PMC article

Abstract

Purpose: Cancer antigen 15-3 (CA15-3) is a serum tumor marker for breast cancer (BC) extensively used in clinical practice. CA15-3 is non-invasive, easily available, and a cost-effective tumor marker for immediate diagnosis, monitoring and prediction of BC recurrence. We hypothesized that an elevation of CA15-3 may have prognostic impact in patients with early BC with normal serum CA15-3 level.

Methods: This was a retrospective cohort study, which included patients with BC who received curative surgery at a comprehensive single institution between 2000 and 2016. CA15-3 levels from 0 to 30 U/mL were considered normal, and patients who had CA15-3 > 30 U/mL, were excluded from the study.

Results: The mean age of study participants (n = 11,452) was 49.3 years. The proportion of participants with elevated CA15-3 ≥ 1 standard deviation (SD) compared with the previous examination during follow-up was 23.3% (n = 2,666). During the follow-up (median follow-up 5.8 years), 790 patients experienced recurrence. The fully-adjusted hazard ratio (HR) for recurrence comparing participants with stable CA15-3 level to subjects with elevated CA15-3 level was 1.76 (95% confidence interval [CI], 1.52-2.03). In addition, if the CA15-3 was elevated ≥ 1 SD, the risk was much higher (HR, 6.87; 95% CI, 5.81-8.11) than in patients without elevated CA15-3 ≥ 1 SD. In sensitivity analysis, the recurrence risk was consistently higher in participants with elevated CA15-3 levels than in participants without elevated CA15-3 levels. The association between elevated CA15-3 levels and incidence of recurrence was observed in all subtypes and the association was stronger in patients with N+ than in patients with N0 stage (p-value for interaction < 0.01).

Conclusion: The results of the present study demonstrated that elevation of CA15-3 in patients with early BC and initial normal serum CA15-3 levels has a prognostic impact.

Keywords: Breast Neoplasms; Prognosis; Survival.