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Erschienen in: Breast Cancer Research and Treatment 2/2017

10.08.2017 | Preclinical study

HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma

verfasst von: Yanjun Hou, Hiroaki Nitta, Lai Wei, Peter M. Banks, Bryce Portier, Anil V. Parwani, Zaibo Li

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2017

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Abstract

Purpose

Anti-HER2 neoadjuvant chemotherapy has been widely used in HER2-positive breast cancer patients; however, pathologic complete response (pCR) is achieved in only 40–50% of patients. The aim of this study was to investigate the association of HER2 intratumoral heterogeneity (ITH) with response to anti-HER2 neoadjuvant chemotherapy.

Methods

Assessment of HER2 ITH was performed on whole tissue sections of pre-treatment samples from a cohort of 64 invasive breast carcinoma cases originally considered positive for HER2 and treated with anti-HER2 neoadjuvant chemotherapy. Both HER2 gene signal and protein expression were simultaneously evaluated by means of a single-slide dual assay, designated as a HER2 gene-protein assay (GPA). HER2 GPA was carried out as well on surgical resection tissues from 25 cases with incomplete therapeutic response.

Results

Nineteen of 64 cases (30%) showed HER2 ITH. Significantly more cases with HER2 ITH were found in the incomplete response group (56%, 14/25) than in the pCR group (13%, 5/39). Patients without ITH detectable by GPA had a 76% pCR outcome (34/45), as compared to 26% (5/19) for those with detectable ITH. Multivariate analysis demonstrated HER2 ITH, progesterone receptor positivity, and relatively low HER2/chromosome 17 centromere ratio to be significantly associated with incomplete response.

Conclusions

HER2 ITH analyses conducted with GPA method revealed that HER2 ITH is an independent factor predicting incomplete response to anti-HER2 neoadjuvant chemotherapy.
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Metadaten
Titel
HER2 intratumoral heterogeneity is independently associated with incomplete response to anti-HER2 neoadjuvant chemotherapy in HER2-positive breast carcinoma
verfasst von
Yanjun Hou
Hiroaki Nitta
Lai Wei
Peter M. Banks
Bryce Portier
Anil V. Parwani
Zaibo Li
Publikationsdatum
10.08.2017
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2017
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-017-4453-8

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