Predictive value of serum HER2 and CA 15-3 in patients with HER2 positive breast cancer and relapse of the disease: Preliminary study.

Background: Cancer antigen (CA) 15-3 is encoded by the MUC1 gene. It is overexpressed in breastcancer (BC) tissue, and released into the bloodstream. The 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 role of circulating HER2 and CA 15-3 as predictive markers of relapse of the disease and in monitoring therapy in patients with metastatic BC are not well defined. The aim of this study was to analyze, whether correlation exists between preoperative serum CA 15-3 and HER2, and relapse ofthe disease in patients who underwent surgery for tissue HER2 positive (HER2+) BC. Materials and Methods: Data regarding a series of 12 women (median age 57 years, range 35-62 years) withstage I (pT1, N0-1mi, M0) tissue HER2+ BC (Group 1) who developed locoregional or distant metastases during follow-up were reviewed. Controls were 14 women with age- and stage-matched tissue HER2+ BC (Group 2) who did not developed relapse of the disease. All patients underwent preoperative CA 15-3 and HER2 serum levels measurement, by a two-site sandwich immunoassay using direct chemiluminescent technology, and enzyme-linked immunosorbent assay (ELISA), respectively. A serum CA 15-3 and HER2 concentration of 30 U/mL and 15 ng/mL were defined as the upper limit of normal, respectively. A p-value<0.05 was considered statistically significant. Results: Overall, the mean preoperative CA 15-3 and HER2 levels were 26.0±10.8 U/mL and 18.5±9.3 ng/mL, respectively. CA 15-3 and HER2 were above the cut-off in 7 and 10 patients of Group 1, respectively. The sensitivity, specificity, positive predictive value (PPV), negative predictivevalue, and negative likelihood ratio weighted by prevalence were (CA15-3 vs.HER2) 0.78 vs. 0.77 (p=0.86), 0.70 vs. 0.85 (p=0.011), 0.58 vs. 0.83 (p<0.001), 0.85 vs. 0.78 (p=0.20), and 0.17 vs. 0.27 (p=0.08), respectively. A weak correlation between CA 15-3 and HER2 (R=0.46, p=0.05) was found. There was nosignificant relationship between age of the patients, CA 15-3 (R=-0.28, p=0.25) or HER2 (R=0.02, p=0.92). Conclusions: In patients with HER2+ stage I BC, baseline serum CA 15-3 and HER2 are independent of age. Both have low sensitivity in detecting primary tumor, but the specificity and PPV of HER2 were significantly higher than that of CA 15-3. These serum markers do not condition the therapeutic decision-making of patients, but are useful as prognostic factor in patients who will develop locoregional or distant metastases during follow-up. References: Lumachi F et al. Curr Med Chem 20: 596-604, 2013.