Accuracy of serum HER2 and CA 15-3 together in early detection of breast cancer recurrence. A preliminary case-control study

Background: Breast cancer is the most common female cancer worldwide, and the 5-year recurrence rates range from 7% to 13%, according to the stage (I-III) of the disease. Because late detection of metastases can contribute to the failure of primary treatment, their early identification has a substantial impact on adequate therapy and prognosis. In this setting, several serum tumor markers (TM) and tissue-extracting prognostic factors have been tested. Unfortunately, none has shown such a sensitivity to be recommended as a routine test. Human epidermal growth factor receptor 2 (HER2) is a transmembrane glycoprotein with intracellular tyrosine kinase activity, that can also be measured in the blood. The monoclonal antibody of the cancer antigen (CA) 15-3 assay recognizes an epitope localized in a mucine glycoprotein encoded by the gene MUC1, and this protein is overexpressed in BC cells and shed into the bloodstream. The purpose of this study was to evaluate the usefulness of HER2 and CA 15-3 serum levels measurements in the early detection of cancer recurrence in women who underwent curative surgery for stage I-II BC invasive ductal carcinoma of the breast. Materials and Methods: Nineteen women (median age 62 years, range 38-74) who underwent curative surgery for stage I-II BC and developed distant metastases during follow-up (cases) were enrolled in the study. Controls were 21 age- and stage-matched patients at the time of surgery, in whom a recurrence was excluded by whole body 18F-FDG-PET/CT. All patients had undergone serum HER2 and CA 15-3 measurements using two-site sandwich immunoassay and direct chemiluminescent technology. The cut-off limit was 32 U/mL and 15 ng/mL for CA 15-3 and HER2, respectively. The chi-squared test was used to compare results. Results: The results (HER2 vs. CA 15-3) were the following: sensitivity 52.6% vs. 36.8% (p=0.022), specificity 81.0 vs. 76.2% (p=0.39), positive predictive value 71.4% (95% CI 45.3-88.3) vs. 58.3% (95% CI 31.9-80.7) (p=0.054), negative predictive value 65.4% (95% CI 46.2-80.6) vs. 57.1% (95% CI 39.1-73.5) (p=0.19), accuracy 67.5% vs. 57.5% (p=0.14). The prevalence was the same (47.5%). With the combination of CA 15-3 and HER2, the sensitivity, specificity and accuracy reached 63.1% (p=0.15), 85.7% (p=0.34), and 75.0% (p=0.21), respectively. Conclusions: In the early detection of distant metastases in patients with BC, the sensitivity of both serum HER2 and CA 15-3 was low. HER2 was more sensitive than CA 15-3 (52.6% vs. 36.8%, p=0.02), but the combination of HER2 and CA 15-3 did not improve significantly (p=NS) the results, and thus is not recommended.