Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns

Q: How were patients grouped based on HER2 FISH results?

Patients were divided into three groups using HER2/CEP17 ratios and HER2 copy numbers, along with HER2 immunohistochemistry scores (2/3+). Group A used HER2/CEP17<2.0 with copy number ≥6.0; group B used HER2/CEP17≥2.0 with copy number ≥4.0 and <6.0; group C used HER2/CEP17≥2.0 with copy number ≥6.0.

Q: Which group had the lowest pathological complete response (pCR) rate?

Group B had the lowest pCR rate at 5.0%. Group A had 33.3% and group C had 44.4%.

Q: What is the main conclusion about anti-HER2 NACT benefit?

Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 did not benefit to the same extent from current anti-HER2 therapies as patients with other FISH patterns.

Sep 23, 2026

Uploaded by Stanley

Study investigates how different HER2 fluorescence in situ hybridisation (FISH) patterns influence responses to anti-HER2 neoadjuvant chemotherapy (NACT) in HER2-positive invasive breast cancer. A cohort of 527 patients treated with anti-HER2 NACT from 2015–2022 was stratified into three FISH groups using HER2/CEP17 ratios and HER2 copy number thresholds. Clinicopathological features and pathological complete response (pCR) rates were compared. Results show the lowest pCR in group B, while group A and group C achieved substantially higher pCR rates. Multivariate analysis links the HER2 FISH pattern to pCR outcome, suggesting group B benefits less from current anti-HER2 therapy.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Introduction

What is already known on this topic

What this study adds

How this study might affect research, practice or policy

Original research Response to anti-HER2 neoadjuvant chemotherapy in HER2-positive invasive breast cancers with different HER2 FISH patterns Hong Lv , 1,2,3 Qian-Ming Bai,1,2,3 Ming Li, 1,2,3 Meng-Yuan Cai,1,2,3 Shu-Ling Zhou,1,2,3 Yin Liu,4 Zhong-Hua Wang,5 Ruo-Hong Shui , 1,2,3 Hong-Fen Lu,1,2,3 Xiao-Li Xu , 1,2,3 Bao-Hua Yu , 1,2,3 Xiao-Yu Tu,1,2,3 Rui Bi , 1,2,3 Yu-Fan Cheng,1,2,3 Xiao-Yan Zhou , 1,2,3 Zhi-Min Shao,4 Wen-Tao Yang1,2,3 ► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1136/jcp-2023-209069](10.1136/jcp-2023-209069)) . 1Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China 3Institute of Pathology, Fudan University, Shanghai, China 4Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China 5Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China Correspondence to Dr Wen-Tao Yang, Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 20032, China; [yangwt2000@163.com](yangwt2000@163.com) HL and Q-MB contributed equally. Received 15 July 2023 Accepted 24 January 2024 © Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. To cite: Lv H, Bai Q-M, Li M, et al. J Clin Pathol Epub ahead of print: [please include Day Month Year] . doi:10 . 1136/jcp-2023- 209069 ABSTRACT Aims Human epidermal growth factor receptor 2 (HER2)-positive patients with breast cancer may have different HER2/CEP17 ratios and HER2 copy numbers, with inconsistent responses to anti-HER2 neoadjuvant chemotherapy (NACT) . Our study aimed to explore the relationship between different HER2 fluorescence in situ hybridisation (FISH) patterns in HER2-positive patients with breast cancer and responses to anti-HER2 NACT. Methods 527 patients with HER2-positive invasive breast cancer who received anti-HER2 NACT from 2015 to 2022 were included and divided into three groups by FISH results, namely group A: HER2/CEP17<2 .0 and HER2 copy numbers ≥6 .0, HER2 immunohistochemistry 2/3+; group B: HER2/CEP17≥2 .0 and HER2 copy numbers ≥4 .0 and <6 .0; group C: HER2/ CEP17≥2 .0 and HER2 copy numbers ≥6 .0. We compared clinicopathological characteristics and pathological complete response (pCR) rates of different groups. Results According to HER2 FISH results, 12 patients (2 . 3%, 12/527) were in group A, 40 (7 .6%, 40/527) were in group B and 475 (90 . 1%, 475/527) were in group C. The pCR rate was the lowest in group B (5 .0%), while the pCR rates in group A and group C were 33. 3% and 44.4%, respectively (p (group A vs. B) =0.021, p (group C vs. B) < 0.001) . Both univariate and multivariate analyses revealed that HER2 FISH pattern was correlated with pCR rate (p (group C vs. B) < 0.001, p (group C vs. B) = 0.025) . Conclusions Patients with HER2/CEP17≥2 .0 and HER2 copy numbers ≥4 .0 and <6 .0 do not benefit to the same extent from current anti-HER2 therapies as FISH-positive patients with other patterns. INTRODUCTION Human epidermal growth factor receptor 2 (HER2) is one of the biomarkers routinely tested in invasive breast cancer. HER2-positive breast cancer patients account for 15%–20% of all breast cancer cases.1 HER2 positivity is associated with a highly aggressive clinical course in breast cancer. Moreover, HER2-positive status is an important predictive marker of response to anti-HER2 targeted therapy.2 Adjuvant chemotherapy plus anti-HER2 targeted treatment may prolong disease-free survival (DFS) and improve the prognosis of HER2-positive patients.3 WHAT IS ALREADY KNOWN ON THIS TOPIC | ⇒ The response of HER2-positive patients to trastuzumab was positively related to the average HER2 copy number. Moreover, patients with

FAQs

How were patients grouped based on HER2 FISH results?

Patients were divided into three groups using HER2/CEP17 ratios and HER2 copy numbers, along with HER2 immunohistochemistry scores (2/3+). Group A used HER2/CEP17<2.0 with copy number ≥6.0; group B used HER2/CEP17≥2.0 with copy number ≥4.0 and <6.0; group C used HER2/CEP17≥2.0 with copy number ≥6.0.

Which group had the lowest pathological complete response (pCR) rate?

Group B had the lowest pCR rate at 5.0%. Group A had 33.3% and group C had 44.4%.

What is the main conclusion about anti-HER2 NACT benefit?

Patients with HER2/CEP17≥2.0 and HER2 copy numbers ≥4.0 and <6.0 did not benefit to the same extent from current anti-HER2 therapies as patients with other FISH patterns.

Sep 23, 2026

Uploaded by Stanley