CA 15-3 and CEA: Not So Novel, But Useful Breast Cancer Tumor Markers
By William B. Ershler, MD, Editor
Abstract & Commentary
Synopsis: In a retrospective analysis of 740 patients with stage I-III breast cancer, preoperative serum levels of CA 15-3 and CEA were both shown to relate to important clinical outcomes, including disease-free and overall survival.
Source: Park B-W, et al. Preoperative CA 15-3 and CEA serum levels as predictor for breast cancer outcomes. Ann Oncol. 2008;19:675-681.
There remains uncertainty on the overall value of circulating tumor markers in the management of breast cancer. To address this, Park and colleagues from Yonsei University Medical College in Seoul, South Korea examined the association between certain tumor markers [cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA)] and clinicopathological parameters and patient outcomes in breast cancer. For this, a total of 740 patients with stages I-III breast cancer had preoperative CA 15-3 and CEA concentrations measured. Elevated preoperative levels of CA 15-3 and CEA were identified in 92 (12.4%) and 79 (10.7%) patients, respectively.
Outcomes, including disease-free and overall survival were examined by univariate and multivariate analyses, and other prognostic factors, including patient age, tumor size, nodal status and the presence or absence of hormone receptors were included.
As expected, young age (<35 years), larger tumor size (> 2cm), axillary node metastases and negative estrogen receptor expression were all negative prognostic factors. Additionally, elevated preoperative level of CA 15-3 and CEA were additional independent negative prognostic factors when examined by Cox multivariate analysis.
Tumor size (>5 cm), node metastases (³ 4), and advanced stage (³ III) were associated with higher preoperative levels. Elevated CA 15-3 and CEA levels were associated with poor disease-free survival (DFS, P = 0.0014, P = 0.0001, respectively) and overall survival (OS, P = 0.018, P = 0.015) even when matched for stage. Patients with normal levels of both CA 15-3 and CEA exhibited better DFS and OS. By multivariate analysis, age (< 35 years), tumor size (> 2 cm), node metastases, estrogen receptor expression, and elevated CA 15-3 and CEA preoperative values were independent prognostic factors for DFS. Additionally, if the results of both tumor markers were combined (ie, 0, 1 or 2 elevated) the prognostic value was significantly enhanced. Patients with both markers in the normal range had significantly better disease-free and overall survival, when compared to those with either 1 or both markers elevated.
Commentary
High preoperative CA 15-3 and CEA levels may reflect tumor burden and are associated with advanced disease and poor outcome. Measuring preoperative levels of CA 15-3 and CEA can be helpful for predicting outcomes and for risk-stratifying in clinical trials.
These days, novel adjuncts to the traditional prognostic factors (age, nodal status, hormone receptors, etc.) have gained popularity. These include HER2 expression status, multigene assay,1 and gene expression profiling.2,3 As valuable as these techniques have become, they rely on tissue which is oftentimes not readily accessible. The current report highlights the potential importance of selected serum markers in breast cancer management. CA 15-3 and CEA, which are of virtually no value in screening, due to both low sensitivity and specificity, can be very useful in predicting important clinical outcomes for those known to have the disease. It appears from this retrospective approach that preoperative levels can be useable indicators of overall tumor burden. It remains to be shown how reliable and useful these measures are once complex treatment programs are undertaken.
References
1. Paik S, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. NEJM. 2004;351(27):2817-2826.
2. van de Vijver MJ, et al. A gene-expression signature as a predictor of survival in breast cancer. NEJM. 2002;347(25):1999-2009.
3. van't Veer LJ, et al. Gene expression profiling predicts clinical outcome of breast cancer. Nature. 2002;415(6871):530-536.
In a retrospective analysis of 740 patients with stage I-III breast cancer, preoperative serum levels of CA 15-3 and CEA were both shown to relate to important clinical outcomes, including disease-free and overall survival.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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