Analytical requirements and standardization of CA 15-3.

The CA 15-3 assay could play, probably in combination with cytokeratin markers, a role in the detection of early recurrence and in monitoring therapy in metastatic breast cancer patients. The CA 15-3 assay is, however, not useful for early detection of breast cancer and has no prognostic significance. The analyte is not clearly defined and a primary reference material cannot be synthesized. A reference measurement procedure is not available and many commercial assays use the original Centocor IRMA as such. The comparability of different CA 15-3 assays is not sufficient according to the results of EQAS. The general recommendations of analytical requirements for tumour marker determinations specified by the working group "Quality Control and Standardization" (Hamburger Symposia on Tumour Markers) includes intra-assay and inter-assay precision, drift, carry-over, dilution effect and high-dose hook effect. From a medical point of view reference limits should be established. Specificity/sensitivity profiles should preferentially be represented by ROCcurves. Confounding factors should be analyzed. To improve the clinical value of CA 15-3, the following needs for improvement have been identified: > Standardization of response criteria during treatment; > Definition of significant increase at recurrence; > Investigation of the biological variance during follow-up; > Definition of the analyte; > Preparation of reference material; > Development of an accepted reference method; > Integration of different international activities and > Optimizing decision-making criteria and clinical application.