Detection of serum HER2 in patients treated with neratinib or trastuzumab: analysis of the I-SPY Trial

TL;DR

This study examines serum HER2 levels in breast cancer patients treated with HER2-targeting drugs to explore its potential as a biomarker for treatment response.

Contribution

The study evaluates serum HER2 as a potential biomarker for HER2-targeted therapies in both HER2-positive and HER2-negative/low tumors.

Findings

26% of HER2-negative patients and 56% of HER2-positive patients had elevated serum HER2 levels.

Serum HER2 levels declined with neoadjuvant therapy, but this decline was not predictive of pathologic complete response.

Serum HER2 was detected in both HER2 tissue-positive and tissue-negative tumors.

Abstract

Drugs targeting human epidermal growth factor receptor 2 (HER2) have fundamentally changed the way breast cancer is treated. Measurement of HER2 expression has become increasingly important with the approval of therapies targeting a HER2-low population. Furthermore, predictive biomarkers for HER2 response would aid the clinical use of these drugs, and a blood-based assay of HER2 could provide important information for therapeutic options for patients.

To evaluate serum HER2 (sHER2) as a potential biomarker for breast cancer response, we examined the serum samples from patients treated with neratinib or trastuzumab combined with paclitaxel obtained from the I-SPY2 neoadjuvant trial. This trial included both HER2-positive and HER2-negative/low tumors.

Of the patients with HER2-negative tumors, 26% had elevated sHER2, while 56% of the HER2-positive patients had elevated sHER2. The sHER2 levels declined with neoadjuvant therapy, and most patients had a clinical response to therapy. However, the sHER2 decline was not predictive of pathologic complete response.

sHER2 was detected in patients with HER2 tissue-positive and tissue-negative tumors. Further study will be needed to determine whether sHER2 is associated with patients with tumors that are HER2-low or ultralow and whether changes in sHER2 over time could predict response to HER2-targeted drugs.

clinicaltrails.gov, identifier NCT01042379.

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