Predictive significance of HER2 intratumoral heterogeneity, determined by simultaneous gene and protein analysis, for resistance to trastuzumab-based treatments for HER2-positive breast cancer

2021 ◽  
Author(s):  
Rie Horii ◽  
Hiroaki Nitta ◽  
Masanori Nojima ◽  
Reo Maruyama ◽  
Takayuki Ueno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Analysis ◽  
Intratumoral Heterogeneity ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer

Quantification of intratumoral heterogeneity of HER2 status in breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 1036-1036
Author(s):  
Rie Horii ◽  
Masaaki Matsuura ◽  
Hiro Nitta ◽  
Yoshinori Ito ◽  
Shinji Ohno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Cells ◽  
Intratumoral Heterogeneity ◽  
Gene Copy ◽  
Her2 Status ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Protein Status ◽  
Positive Breast Cancer

1036 Background: Intratumoral heterogeneity (ITH) occurs as a consequence of epigenetic aberrations in tumor cells with genetic diversity. HER2 ITH can be classified into genetic (a mixture of tumor cells with and without HER2 gene amplification) and epigenetic ITH (a mixture of HER2 gene-amplified tumor cells with and without HER2 protein overexpression). However, the both effects of genetic and epigenetic ITH on HER2-targeted therapy have not been clearly demonstrated. In order to implement ITH as a referenced factor for treatment selection, the ITH quantification is necessary. Gene-protein assay (GPA), in which immunohistochemistry and dual in situ hybridization are simultaneously performed on a single slide, allows bright-field analyses of both gene and protein status. We aimed to quantify HER2 ITH by the combination of gene and protein status and clarify its clinical significance. Methods: Fifty three patients with HER2-positive breast cancer, who underwent neoadjuvant trastuzumab with chemotherapy, were examined. Five representative microscopic images were captured from a GPA slide of a pre-therapeutic biopsy material. All evaluable tumor cells in the images were scored according to the HER2 status determined by the combination of gene copy number and protein expression (Table). We investigated the relationship between the HER2 scores and pathological complete response (pCR) to the neoadjuvant treatment by the logistic analysis. Results: The average of HER2 scores, indicating the degree of the HER2 status, varied from 2.21 to 5.98. It was significantly related to pCR (Estimate: 1.21, Std. error: 0.46, RR: 3.34, P=0.009, 95%CI: 1.35-8.25). The standard deviation of HER2 scores, indicating the degree of the HER2 ITH, varied from 0.13 to 1.37. It was significantly related to pCR (Estimate: -2.09, Std. error: 0.83, RR: 0.12, P=0.012, 95%CI: 0.02-0.63). Conclusions: HER2 ITH, quantified by GPA, is a predictive factor for the therapeutic effect to trastuzumab-based treatment in HER2-positive breast cancer. [Table: see text]

Review of treatment strategies for HER2 positive breast cancer and their implementation in a major Swiss hospital

2020 ◽  
Author(s):  
F Geissler ◽  
M Vetter ◽  
A Schoetzau ◽  
C Montavon ◽  
C Kurzeder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Strategies ◽  
Her2 Positive ◽  
Her2 Positive Breast Cancer ◽  
Positive Breast Cancer
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