Meaningful interpretation of serum HER2 ECD levels requires clear patient clinical background, and serves several functions in the efficient management of breast cancer patients

• Serum ECD and tissue HER2 levels are consistent in untreated tumor-bearing patients.
• The prognostic value of serum ECD was demonstrated using cut-off of 15.0 ng/ml.
• Patients with elevated ECD had shorter progression-free survival (PFS).
• Elevated ECD was an adverse predictor for PFS in response to anti-HER2 therapy.
• ≥ 20% decreased ECD was associated with longer PFS in the patients.

BackgroundThis study was initiated to evaluate the clinical significant of HER2 extracellular domain (ECD) in the real-time management of breast cancer patients.MethodsFive-hundred forty-six eligible breast cancer patients were divided according to their clinical background. The correlation between ECD, tissue HER2, and clinical outcome of the patients were analyzed.ResultsReceiver operating characteristic analysis revealed that ECD measured before receiving neoadjuvant therapy yielded the highest area under the curve (0.9185; P < 0.0001), indicating that ECD and tissue HER2 levels are consistent in untreated tumor-bearing patients. At cut-off of 15.0 ng/ml, the prognostic value of ECD was demonstrated using univariate (HR = 1.664, P < 0.0001) and multivariate (HR = 1.547, P = 0.011) Cox regression analysis. Kaplan-Meier survival curves revealed that patients with elevated ECD had shorter progression-free survival (PFS) (4.0 vs. 6.1 months, P < 0.0001). Elevated ECD was also an adverse predictor for PFS in response to anti-HER2 therapy (4.3 vs. 10.2 months, P = 0.0155). In contrast, ≥ 20%, decreased ECD was associated with longer PFS in patients who received anti-HER2 therapy (10.9 vs. 2.4 months, P = 0.0164) and overall (10.7 vs. 2.8 months, P = 0.0034).ConclusionsA patient's clinical history can help determine whether ECD could provide added value for breast cancer management.