Serum HER2 in combination with CA 15-3 as a parameter for prognosis in patients with early breast cancer

• It is the first analysis evaluating the prognostic value of serum HER2 with CA 15-3 in breast cancer.
• Sera of breast cancer patients were correlated with clinicopathological parameters and outcome.
• Serum HER2 and CA 15-3 are independent prognostic factors for a worse disease free survival.
• The combination of both could identify high-risk breast cancer patients.

AimHER2 in breast cancer tissue is a marker of high prognostic and predictive relevance. Soluble HER2, the extracellular domain of the HER2/neu receptor (HER2 ECD), which is shed into the blood, has been suggested to be a helpful tumor marker. We investigated the relationship between the concentrations of HER2 ECD, CEA and CA 15-3, the association of these markers with clinicopathological features and the impact of HER2 ECD alone and in combination with known prognostic factors on disease free survival (DFS) and cancer specific survival (CSS) in untreated early breast cancer patients.Patients and methodsHER2 ECD (ADVIA, Bayer), CEA (AxSYM, Abbott) and CA 15-3 (Elecsys, Roche) were measured at time of primary diagnosis in the pre-therapeutic (pre-operative) sera of 241 breast cancer patients and were correlated with clinicopathological parameters and outcome.ResultsHigher HER2 ECD levels were significantly correlated with postmenopausal status (p = 0.016) and tissue HER2-overexpression (p < 0.0001). Higher serum levels of CA 15-3 were associated with larger tumor size (p = 0.019), positive lymph nodes (p = 0.019), UICC stage III (p < 0.01), positive tissue HER2-overexpression (p < 0.05) and negative hormone receptor status (p = 0.016). In multivariate analysis, serum HER2 ECD levels, CA 15-3 levels, large tumor size and negative hormonal status were independent prognostic factors in DFS. Patients with both high levels of HER2 ECD (> 15 ng/mL) and high serum levels of CA 15-3 (> 24 U/mL) had the poorest prognosis with a DFS after 3 years of 50.0%. Patients without elevated serum levels had a better outcome with a DFS of 91.2%.ConclusionsIn our retrospective analysis, HER2 ECD and CA 15-3 were independent and better prognostic tools than HER2 in tissue. Prospective validation is necessary to confirm their usefulness in clinical practice.