Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer - A Retrospective Multicenter Cohort Study

Q: What was the study’s main goal when comparing HER2 (3+) with HER2 (2+)/ISH+ early-stage breast cancer?

The study evaluated neoadjuvant therapeutic response, long-term outcomes, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ early-stage breast cancer patients.

Q: How did pathologic complete response (pCR) differ between the HER2 (3+) and HER2 (2+)/ISH+ groups?

In cohort 1, HER2 (3+) had a higher pCR rate (38.9%) than HER2 (2+)/ISH+ (18.1%), with a statistically significant difference.

Q: Did adding trastuzumab or trastuzumab plus pertuzumab improve outcomes in both HER2 categories?

These targeted regimens improved pCR rates and disease-free survival in HER2 (3+) breast cancer, but the improvement was not observed in HER2 (2+)/ISH+ breast cancer.

Sep 21, 2026

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Objective evaluation of neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity in HER2-positive early-stage breast cancer stratified by immunohistochemistry HER2 (3+) versus HER2 (2+)/in situ hybridization (ISH+) categories. Two retrospective multicenter cohorts were analyzed, including patients receiving neoadjuvant therapy and surgery. HER2 (3+) showed higher pathologic complete response, while disease-free survival was broadly comparable, with targeted regimen benefit varying by subtype.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Background

Methods

Cohort 1 (C1)

Cohort 2 (C2)

Results

Pathologic complete response and survival

Intrinsic subtype and HER2E enrichment

Conclusions

Implications for Practice

Introduction

Comparison of the Response to Neoadjuvant Therapy Between Immunohistochemistry HER2 (3+) and HER2 (2+)/ISH+ Early-Stage Breast Cancer: A Retrospective Multicenter Cohort Study Dechuang Jiao1,†, Guangyu Li1,†, Hao Dai1,†, Jia Wang1, Jiao Zhang1, Yangyang Hou1, Xuhui Guo1, Yajie Zhao1, Xilong Gong1, Zhenzhen Liu*, 1, 1Department of Breast Disease, Henan Breast Cancer Centre, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, People’s Republic of China * Corresponding author: Zhenzhen Liu, Department of Breast Disease, Henan Breast Cancer Centre, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou 450008, People’s Republic of China. Email: [zlyyliuzhenzhen0800@zzu.edu.cn](zlyyliuzhenzhen0800@zzu.edu.cn) †These authors contributed equally to this work. Abstract Background: According to the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) criteria, both immunohistochemical HER2 (3+) and HER2 (2+)/in situ hybridization (ISH) amplified [HER2 (2+)/ISH+] breast cancers (BCs) fall under the HER2-positive BC category. However, there is a lack of studies exploring the difference of neoadjuvant therapeutic response between patients with HER2 (3+) and HER2 (2+)/ISH+ early BC. We aimed to evaluate the neoadjuvant therapeutic response, long-term outcome, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ BC. Methods: We examined 2 distinct cohorts. Cohort 1 (C1) encompassed 2648 patients with HER2-positive early BC diagnoses, and they received neoadjuvant therapy (NT) and surgery between January 1, 2009 and December 31, 2022, from the Shanghai Jiao Tong University Breast Cancer Data Base. Cohort 2 (C2) comprised 135 patients with early-stage HER2-positive BC who underwent NT and surgery at Henan Cancer Hospital from January 1, 2021, to December 31, 2022. These patients had available genomic and transcriptomic data at their disposal. C1 and C2 were further categorized into 2 patient cohorts as follows: (1) patients with IHC HER2 (3+) early BC [HER2 (3+) group],(2) patients with HER2 (2+)/ISH+ early BC [HER2 (2+)/ISH+ group] . Among those excluded from the analysis were patients < 18 years or >80 years of age. Clinicopathological parameters, long-term outcomes, and intrinsic subtypes were analyzed. Results: In the C1 population, 83.7% had HER2 (3+) BC, while 16.3% had HER2 (2+)/ISH+ BC. Patients with HER2 (3+) had a significantly higher pathological complete response (PCR) rate (38 .9%) than patients with HER2 (2+)/ISH+ (18 . 1%; P < .001), but the disease-free survival (DFS) was comparable after a median follow-up of 29 months ( P = . 556) . The addition of trastuzumab or trastuzumab plus pertuzumab toneoadjuvant chemotherapy (NAC) improved PCR rates and DFS in HER2 (3+) BC but not in HER2 (2+)/ISH+ BC. In the C2 population, 97.75% HER2 (3+) and 52. 17% HER2 (2+)/ISH+ were HER2 enriched (HER2E) subtype ( P < .001) . HER2E showed increased PCR rates compared to non-HER2E ( P = .004) . Conclusions: Compared to HER2 (3+) BC, the limited effectiveness of neoadjuvant trastuzumab and pertuzumab therapy for HER2 (2+)/ISH+ BC is due to subtype heterogeneity. Reassessment of targeted therapy efficacy in patients with HER2 (2+)/ISH+ BC is essential. Key words: HER2; neoadjuvant therapy; breast cancer; immunohistochemistry. Implications for Practice This cohort investigation provides compelling evidence of a significant difference in the response to neoadjuvant therapy between patients with HER2 (3+) and HER2 (2+)/ISH+ . Patients with HER2 (2+)/ISH+ encounter challenges in deriving benefit from neoadjuvant targeted therapy, potentially due to intrinsic subtype differences. Based on our findings, we recommend considering HER2 protein expression when making neoadjuvant targeted treatment recommendations for patients with early-stage HER2-positive breast cancer. Reevaluation of the value of target

FAQs

What was the study’s main goal when comparing HER2 (3+) with HER2 (2+)/ISH+ early-stage breast cancer?

The study evaluated neoadjuvant therapeutic response, long-term outcomes, and intrinsic subtype heterogeneity between HER2 (3+) and HER2 (2+)/ISH+ early-stage breast cancer patients.

How did pathologic complete response (pCR) differ between the HER2 (3+) and HER2 (2+)/ISH+ groups?

In cohort 1, HER2 (3+) had a higher pCR rate (38.9%) than HER2 (2+)/ISH+ (18.1%), with a statistically significant difference.

Did adding trastuzumab or trastuzumab plus pertuzumab improve outcomes in both HER2 categories?

These targeted regimens improved pCR rates and disease-free survival in HER2 (3+) breast cancer, but the improvement was not observed in HER2 (2+)/ISH+ breast cancer.

Sep 21, 2026

Upload by Noah