Tumor markers in the early detection of tumor recurrence in breast cancer patients: CA 125, CYFRA 21-1, HER2 shed antigen, LDH and CRP in combination with CEA and CA 15-3

• A reproducible tumor marker increase based on individual baseline values is highly effective for early detection.
• The overall sensitivity of tumor detection can be improved by combining biomarkers.
• The use of CA 125 in combination with CEA and CA 15-3 can be a useful tool in follow-up.

BackgroundKinetics of CA 15-3 and CEA have a high specificity in the early detection of metastatic breast cancer (MBC). However, this high specificity is associated with a lack of sensitivity. To decrease the number of false negative patients, the additional diagnostic potential of an extended panel of biomarkers was evaluated.MethodsThis analysis was performed as part of a large follow-up study (1998–2010) evaluating 813 patients with a median follow-up of 63 months.After primary therapy, all patients underwent tumor marker monitoring for CEA and CA 15-3 at 6-week intervals. A reproducible previously defined increase (≥ 100%) based on the individual baseline value of each patient was considered as a strong indicator of MBC. For the present analysis, we retrospectively evaluated 1011 blood samples from 95 patients. Forty-seven of these had metastatic disease for the first time at the time of this evaluation, while the remaining 48 patients showed no evidence of disease. The sera of these patients were additionally assessed for the following parameters: cancer antigen (CA) 125, cytokeratin-19 soluble fragment (CYFRA 21-1), HER2 shed antigen, lactate-dehydrogenase (LDH) and C-reactive protein (CRP).Results26 of 47 patients with MBC showed a reproducible tumor marker increase of at least CEA and/or CA 15-3 (55.3%, true-positive). The remaining 21 patients with MBC showed no increase in CEA or CA 15-3 (44.7%, false negative, FN). By combining all markers mentioned above, 41 of 47 patients with MBC showed a reproducible marker increase with a sensitivity of 87.2% and specificity of 100%.ConclusionThis retrospective analysis indicates that a panel of biomarkers can increase the sensitivity of the CA 15-3/CEA combination without loss of specificity. The combined use is therefore helpful for early detection of MBC.