Serum HER‐2/neu and relative resistance to trastuzumab‐based therapy in patients with metastatic breast cancer

Abstract

BACKGROUND.Previous reports based on small patient numbers suggested that changes in serum HER‐2/neu levels may predict response or lack of response to trastuzumab‐based therapies in metastatic breast cancer (MBC). The objectives of this study were to pool data from 307 patients with MBC from 7 medical institutions to validate that the serum HER‐2/neu profile predicts patient resistance to trastuzumab and to establish a clinically relevant cutoff.METHODS.This was an international, multicenter, retrospective analysis of individual pooled data from 307 patients with MBC who were treated with first‐line trastuzumab‐based therapy. Serum was collected at baseline and 30 to 120 days after the initiation of trastuzumab therapy. A serum HER‐2/neu decrease ≥20% (receiver operating curve analysis) was defined as a significant HER‐2/neu change.RESULTS.Of the 307 patients with MBC, 191 patients (62%) had a significant decline (>20%) in serum HER‐2/neu and 116 patients (38%) did not. The objective response rate was 57% for patients who achieved this decline in serum HER‐2/neu (>20%) compared with 28% for patients who did not. Patients who achieved this decline in serum HER‐2/neu also had a significantly longer time to disease progression (320 days vs 180 days; P < .0001), longer duration of response (369 days vs 230 days; P = .008), and longer overall survival (898 days vs 593 days; P < .018).CONCLUSIONS.In this pooled analysis of 307 patients with MBC, individuals who did not achieve a significant decline (≥20%) in serum HER‐2/neu levels had decreased benefit from trastuzumab‐based therapy, and these patients should be considered for clinical trials evaluating additional HER‐2/neu‐targeted interventions. Cancer 2008. © 2008 American Cancer Society.

Plasma Membrane Proteomics and Its Application in Clinical Cancer Biomarker Discovery

“…An elevated serum HER-2/neu level as measured after 2 months of chemotherapy treatment was significantly associated with reduced long term clinical benefit. Serum HER-2/neu was also found to predict response to trastuzumab-based therapies as individuals who did not achieve a significant decline in serum HER-2/neu levels had decreased benefit from trastuzumab-based therapy (169). Many of these findings need confirmation in other independent cohorts; however, overall, they seem promising.…”

Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial

“…In metastatic breast cancer, no clear relationship was found between baseline sHER2 levels and tumor response to trastuzumab-based treatment in a recently published metaanalysis [33], while other groups have suggested a role of sHER2 determination [21,34] so that no definitive conclusions can be drawn [26]. There is limited information regarding sHER2 to predict benefit from trastuzumab treatment in primary breast cancer.…”

“…Receiver operating characteristic (ROC) curve analysis was performed to determine an optimal sHER2 decline during NT corresponding to pCR. A decrease of sHER2 levels of more than 20 percent during NT was regarded as significant in the following analysis (sensitivity 75%, specificity 55%) [21].…”

Resistance to HER2-targeted therapy: mechanisms of trastuzumab resistance and possible strategies to overcome unresponsiveness to treatment

“…In a pooled analysis of 307 patients with metastatic breast cancer, individuals who did not achieve a significant decline (20%) in serum HER2/neu levels were seen to benefit less from trastuzumab-based therapy with or without chemotherapy. A reduction of 20% or more in the serum concentration of the HER2 extracellular domain was associated with increased progression-free and overall survival as compared with patients in whom a less strong reduction was observed (Serum HER2/neu and relative resistance to trastuzumab-based therapy in patients with metastatic breast cancer) [5]. In addition, based on an in vitro study using HER2-overexpressing breast tumor cells, Zabrecky et al, suggested that an extracellular domain can link to antibodies (e.g.…”