Characteristics of HER2-negative breast cancers with FISH-equivocal status according to 2018 ASCO/CAP guideline

Hui Kong,Xiaoyan Zhou,Anqi Li,Qianming Bai,Wentao Yang

doi:10.1186/s13000-021-01187-z

Abstract

BackgroundAccording to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. However, whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated.Methods195 HER2 FISH-equivocal breast cancer samples were collected from 2014 to 2018. The molecular subtype was identified according to 2013 St Gallen consensus, and HER2 status was also re-determined following 2018 ASCO/CAP guideline. All samples were classified into 4 groups according to the average HER2 copy number (4.0–4.4, 4.5–4.9, 5.0–5.4, 5.5–5.9 signals/cell). The relationship between HER2 copy number and clinicopathological parameters was analyzed.Results183 (93.8%) of 195 FISH-equivocal cases were classified as luminal-like subtype, while the other 12 (6.2%) were undetermined. Following 2018 ASCO/CAP guideline, all FISH-equivocal cases were recategorized as HER2 negative. Therefore, 31(15.9%) cases were luminal A-like, 152 (77.9%) were luminal B-like (HER2 negative) and 12 (6.2%) were triple negative. The average HER2 copy number showed a positive correlation with chromosome 17 polysomy, but had no significant association with other clinicopathological parameters as well as prognosis. 17 (8.7%) patients were treated with trastuzumab, but showed no difference in prognosis with those who didn’t receive targeted therapy.ConclusionsIn this study, all HER2 FISH-equivocal breast cancers were recategorized as HER2 negative according to 2018 ASCO/CAP guideline. Most of these patients were luminal B-like (HER2 negative). The average HER2 copy number had no significant association with clinicopathological parameters, as well as prognosis.

Highlights

According to 2018 ASCO/CAP guideline, Human epidermal growth factor receptor 2 (HER2) FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+
The results suggested that the average HER2 copy number showed positive correlation with the presence of chromosome 17
According to the updated guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+

Summary

Introduction

According to 2018 ASCO/CAP guideline, HER2 FISH-equivocal breast cancers will be categorized as HER2 negative except those with IHC 3+. Whether or not HER2 FISH-equivocal breast cancers was a heterogeneous group has not been well illustrated. Human epidermal growth factor receptor 2 (HER2) is involved in the regulations of several key cellular signal pathways in breast cancers, including proliferation, migration, and adhesion [2]. HER2-targeted drugs, such as Trastuzumab, which inhibit downstream signaling of these pathways, are effective for HER2 positive breast cancer patients. HER2 amplification status is mainly determined by immunohistochemistry (IHC) assays for protein overexpression and fluorescence in situ (2022) 17:5 hybridization (FISH) for gene amplification. IHC assays are the first adopted method, HER2 FISH is required when the IHC result is equivocal

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