Recently, serum tumor marker CYFRA 21-1 has shown a high sensitivity and specificity in patients with breast carcinoma as well as an important usefulness in monitoring for recurrence, evaluating the efficacy of the treatment in advanced disease, and acting as an independent prognostic factor.1
Based on these results we tested the sensitivity of CYFRA 21-1 in patients with metastatic breast carcinoma in our institution, before using it as a marker of recurrence in early stages or in the evaluation of the therapeutic effect in advanced disease.
PATIENTS AND METHODS
Between October 2000 and June 2001, serum samples from 40 consecutive patients with confirmed metastatic breast carcinoma were obtained. We simultaneously measured the titers of CYFRA 21-1, carcinoembryonic antigen (CEA), and CA 15.3. The mean patient age was 60.4 years. Most patients had a single metastatic location —25 out of 40, or 62.5%— and the organ most frequently involved was bone in 19 patients (47.5%), followed by the lung in 24% of patients. The cutoff value of CYFRA 21-1 was 3.0 ng/mL, and the recommended cutoff values of CEA and CA 15.3 were 5.0 ng/mL and 51 U/mL, respectively.
A total of 23 patients had CYFRA 21-1 levels higher than the cutoff value. Sensitivity was 57.5%, with titers ranging from 0.10 to 310.6 ng/mL (median, 3.87; mean, 23.96). The sensitivity of CEA and CA 15.3 reached 50% and 45%, respectively (Fig. 1). Considering only the values of CEA and CA 15.3, 26 patients (65%) were positive for at least one of these two markers, and, when CYFRA 21-1 was added, the rate of patients with at least one positive marker increased to 77.5%. In eight cases of negative CYFRA 21-1, the titers of CEA, CA 15.3, or both were positive. There were no statistically significant differences between the sensitivities of the markers.
Although numerous tumor markers for breast carcinoma have been tested, most have not been utilized in clinical practice, with the exception of CEA and CA 15.3. However, the guidelines of the American Society for Clinical Oncology for the use of tumor markers in breast carcinoma conclude that current data are insufficient to recommend either CA 15.3 or CEA for screening, diagnosis, staging, surveillance following primary treatment, or monitoring response to treatment.2 It is well known that breast carcinoma cells express cytokeratin 19 fragments,3 and that these fragments can be detected by CYFRA 21-1.4 Nakata et al. have recently reported a high sensitivity and specificity for CYFRA 21-1 in breast carcinoma as well as a strong value for CYFRA 21-1 as a prognostic factor.1 In our institution, before using CYFRA 21-1 as a routine marker in breast carcinoma, we have confirmed its sensitivity in metastatic disease, with results comparable to those obtained by Nakata et al.
Based on these data, we can conclude that CYFRA 21-1 is a sensitive tumor marker for breast carcinoma when compared with CEA or CA 15.3. In our institution the sensitivity in metastatic breast carcinoma was 57.5%, which is at least equivalent to that obtained in previously reported studies. Measurement of CYFRA 21-1 together with CEA and CA 15.3 may improve the usefulness of these two markers. These results have led us to study the role of CYFRA 21-1 as a predictor of relapse in early breast carcinoma after treatment, as well as its role in monitoring the efficacy of therapies in advanced disease.
1Nakata B, Ogawa Y, Ishikawa T, et al. Serum CYFRA 21-1 is one of the most reliable tumor markers for breast carcinoma. Cancer. 2000; 89: 1285-1290.
2Clinical practice guidelines for the use of tumor markers in breast and colorectal cancer. Adopted on May 17, 1996 by the American Society of Clinical Oncology. J Clin Oncol. 1996; 14: 2843-2877.
3Brotherick I, Robson CN, Browell DA, et al. Cytokeratin expression in breast cancer: phenotypic changes associated with disease progression. Cytometry. 1998; 32: 301-308.
4Pujol JL, Grenier J, Daures JP, Daver A, Pujol H, Michel FB. Serum fragments of cytokeratin subunit 19 measured by CYFRA 21-1 immunoradiometric assay as a marker of lung cancer. Cancer Res. 1993; 53: 61-66.