Introduction The proteolytic breakdown product corresponding to the extracellular domain (ECD) of the HER-2/neu oncoprotein p185 is found in the circulation of healthy individuals and patients having cancers of epithelial origin. For the current evaluation we sought to determine the analytical performance as well as the clinical utility of the newly developed ADVIA Centaur® HER-2/neu assay (Bayer HealthCare LLC, Diagnostics Division, Tarrytown, NY, USA) in monitoring patients with metastatic breast cancer during the course of disease and treatment and to compare the obtained results with those of CA 15–3. Methods The analytical performance (including precision, normal range, interfering substances, minimum detectable concentration, dilution recovery, spiking recovery and high-dose hook effect) were determined. HER-2/neu and CA 15–3 values were measured in retrospective samples obtained from 59 patients with metastatic breast cancer undergoing treatment over a 6–12 month period. Serial changes in serum HER-2/neu and CA 15–3 were correlated with changes in clinical status on a visit-to-visit basis. For each pair of serial measurements, changes of equal to or greater than, or less than 15% for HER-2/neu and 21% for CA 15–3 were considered to indicate progression or lack of progression, respectively. Results The ADVIA Centaur HER-2/neu assay demonstrated within-run imprecision and total imprecision ranging from 3.0–5.6% and from 3.2–5.7%, respectively. The upper limit of normal was 15.2 ng/mL (90% CI: 14.2–17.0 ng/mL). No significant interference (<5%) was seen with bilirubins, hemoglobin, triglycerides and cholesterol or therapeutic drugs commonly present in the sera of breast cancer patients. The minimum detectable concentration (analytical sensitivity) was found to be 0.5 ng/mL. The patient population in the clinical study included breast cancer patients who responded to therapy (stable, partial or complete response) or had disease progression. HER-2/neu levels showed a concordance of 78.1% (82/105 restaging time points) with the clinical course of disease, whereas CA 15–3 levels showed a concordance of 76.2% (80/105 restaging time points). The concordance with clinical status increased to 85.7% (90/105 restaging time points) when both results were used in combination as a series test. Conclusions The ADVIA Centaur HER-2/neu assay provides excellent analytical performance for serial testing of serum HER-2/neu levels. The clinical data demonstrate the usefulness of serum HER-2/neu in monitoring metastatic breast cancer patients during treatment. Furthermore, the results indicate that serum HER-2/neu and CA 15–3 may be useful in identifying disease progression or therapeutic response in different subgroups of women with metastatic breast cancer.
Clinical benefit of treatment after trastuzumab emtansine for HER2-positive metastatic breast cancer: a real-world multi-centre cohort study in Japan (WJOG12519B)
