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Breast Cancer Research and Treatment

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01-04-2020 | Fluorescence in Situ Hybridization | Preclinical Study

Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma

Authors: Aidan C. Li, Jing Zhao, Chao Zhao, Zhongliang Ma, Ramon Hartage, Yunxiang Zhang, Xiaoxian Li, Anil V. Parwani

Published in: Breast Cancer Research and Treatment | Issue 2/2020

Abstract

Purpose

Patients with HER2-positive breast cancer commonly receive anti-HER2 neoadjuvant chemotherapy and pathologic complete response (pCR) can be achieved in up to half of the patients. HER2 protein expression detected by immunohistochemistry (IHC) can be quantified using digital imaging analysis (DIA) as a value of membranous connectivity. We aimed to investigate the association HER2 IHC DIA quantitative results with response to anti-HER2 neoadjuvant chemotherapy.

Methods

Digitized HER2 IHC whole slide images were analyzed using Visiopharm HER2-CONNECT to obtain quantitative HER2 membranous connectivity from a cohort of 153 HER2+ invasive breast carcinoma cases treated with anti-HER2 neoadjuvant chemotherapy (NAC). HER2 connectivity and other factors including age, histologic grade, ER, PR, and HER2 fluorescence in situ hybridization (FISH) were analyzed for association with the response to anti-HER2 NAC.

Results

Eighty-three cases (54.2%) had pCR, while 70 (45.8%) showed residual tumor. Younger age, negative ER/PR, higher HER2 DIA connectivity, higher HER2 FISH ratio and copy number were significantly associated with pCR in univariate analysis. Multivariate analysis demonstrated only age, HER2 DIA connectivity, PR negativity, and HER2 copy number was significantly associated with pCR, whereas HER2 DIA connectivity had the strongest association.

Conclusions

HER2 IHC DIA connectivity is the most important factor predicting pCR to anti-HER2 neoadjuvant chemotherapy in patients with HER2-positive breast cancer.

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Title: Quantitative digital imaging analysis of HER2 immunohistochemistry predicts the response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma
Authors: Aidan C. Li
Jing Zhao
Chao Zhao
Zhongliang Ma
Ramon Hartage
Yunxiang Zhang
Xiaoxian Li
Anil V. Parwani
Publication date: 01-04-2020
Publisher: Springer US
Keywords: Fluorescence in Situ Hybridization
Breast Cancer
Breast Cancer
Trastuzumab
Cytostatic Therapy
Published in: Breast Cancer Research and Treatment / Issue 2/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05546-0

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