Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2‐positive breast cancer receiving chemotherapy with or without trastuzumab: Results from North Central Cancer Treatment Group adjuvant trial N9831

Abstract

Purpose IncreasedsHER2 is an indicator of poor prognosisin HER2+ metastatic breast cancer. This study evaluated the levels of sHER2 during treatment and at time of recurrence in the adjuvant N9831 clinical trial. Patients and Methods Aims were to describe sHER2 levels during treatment and at time of recurrence in patients randomized to Arms A (standard chemotherapy), B (standard chemotherapy with sequential trastuzumab) and C (standard chemotherapy with concurrent trastuzumab). Baseline samples were available for 2318 patients. Serial samples were available from 105 patients and recurrence samples were available from 124 patients. Cutoff for this assay was 15ng/mL. Statistical methods included repeated measures linear models, Wilcoxon rank sum tests, and Cox regression models Results Differences between groups existed by age, menopausal status and hormone receptor status. Within Arms A, B and C, patients with baseline sHER2 ≥ 15ng/mL were found to have worse DFS than patients with baseline sHER2 <15ng/mL (A: HR=1.81, p=0.0014; B: HR=2.08, p=0.0015; C: HR=1.96, p =0.01). Among the 124 patients with disease recurrence, sHER2 levels increased from baseline to time of recurrence in Arm A and Arm B while it remained unchanged in Arm C. Patients with recurrence sHER2 levels ≥ 15ng/mL had shorter survival time following recurrence with 3-year OS of 51% compared to 77% for the <15ng/mL sHER2 group (HR=2.36; 95% CI: 1.19–4.70, p=0.01). Conclusions In early stage HER2-positive breast cancer, high baseline sHER2 level is a prognostic marker associated with shorter DFS and high sHER2 level at recurrence is predictive of shorter survival.

Reproductive risk factors and breast cancer subtypes: a review of the literature

“…Biomarkers could potentially be developed by extending work being conducted in patients with HER2+ breast cancer. For example, the cleaved extracellular domain of HER2, termed soluble HER2 (sHER2), can be detected in the blood of patients with metastatic HER2+ breast cancer and is a prognostic biomarker [54]. …”

Electrohydrodynamic‐Induced SERS Immunoassay for Extensive Multiplexed Biomarker Sensing

“…In addition to this, we also determined the approximate concentrations (Table S1, Supporting Information) of target protein biomarkers from each tested patient and healthy control samples based on the established calibration curves (Figure b). It was observed that the determined target concentrations for each of the relevant biomarkers (HER2‐breast cancer[16a] and MUC16‐ovarian cancer) from patients samples were within the clinically relevant range. [16a] However, the resulting variation in the detected target levels of HER2(+) and MUC16(+) patients could be attributed to the cancer stage and also inherent protein expression of HER2[16b] or MUC16 that could vary across individual patients.…”

“…In this study, simultaneous capture and multiplexed detection was performed on human epidermal growth factor receptor 2 (HER2); Mucin 1, cell surface associated (MUC1); epidermal growth factor receptor (EGFR); and Mucin 16, cell surface associated (MUC16), which are overexpressed in breast, lung, and ovarian cancer, respectively . Notably, HER2 is widely considered as an important biomarker for breast cancer therapy and believed to have close correlation with hormonal therapy and drug treatment . Similarly, MUC16 is potentially the only recommended tumor biomarker for the clinical diagnosis and management of ovarian cancer .…”

Current status of the prognostic molecular biomarkers in breast cancer: A systematic review

“…In the N9831 adjuvant breast cancer trials, early stage HER2-positivity was identified as a biomarker of clinical outcome and disease progression (54). Moreno-Aspitia et al (55) evaluated sHER2 levels at the time of relapse using a sample from the N9831 clinical trial and found that DFS was lower in patients with sHER2 levels >15 ng/ml, compared with patients with lower levels of sHER2 (HR=2.36; 95% CI=1.19-4.70; P=0.01). Therefore, in early stage HER2-positive breast cancer, sHER2 was found to be a suitable prognostic biomarker for relapse, and survival in relapsed patients.…”