Evaluation of the clinical characteristics and potentially prognostic factors in HER2-positive breast cancer

Sep 30, 2026

Retrospective cohort analysis used SEER Plus Database data from January 2000 to December 2019 to evaluate HER2 and hormone receptor (ER/PR) status in breast cancer. HER2-positive breast cancer, although responsive to HER2-targeted therapies, shows variable benefit across patients. The study compared demographic, clinicopathological characteristics, survival outcomes, and differential genes and mutations between HR+ and HR− within HER2+ cases using Pearson’s chi-squared test and transcriptome RNA-seq from TCGA and UCSC Xena. HR+ /HER2+ patients showed lower breast cancer-specific death risk and higher overall survival. Mast cells were enriched in the HR+ /HER2+ group, while plasma cells increased in the HR− /HER2+ group, suggesting HR status and gene alterations may yield prognostic and predictive value for treatment stratification.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

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Introduction

Background on breast cancer heterogeneity and molecular subtypes

HER2 as a therapeutic target and variability in treatment response

Rationale for assessing HR status and prognostic factors in HER2+ disease

Amino Acids (2026) 58:4 [https://doi.org/10.1007/s00726-025-03494-x](https://doi.org/10.1007/s00726-025-03494-x) RESEARCH Evaluation of the clinical characteristics and potentially prognostic factors in HER2-positive breast cancer Liang Shi1 · Pei-Wen Xi2 · Zhi Li3 · Jing Wu4 · Xu Zhang1 · Lei Zhang5 Received: 21 April 2025 / Accepted: 28 November 2025 © The Author(s) 2025 Abstract From January 2000 to December 2019, the SEER Plus Database collecting human epidermal growth factor receptor 2 (HER2) and hormone receptor (HR; including estrogen receptor [ER] and progesterone receptor [PR]) status for breast cancer (BC) cases. HER2-positive (HER2+) BC is an aggressive type, and HER2-targeted therapies have significantly improved the therapeutic outcome of patients. However, not every HER2+ BC patient achieves optimal benefits from current HER2-targeted therapies. Here, we conducted a detailed analysis to compare the demographic and clinic-pathological characteristics, survival, differential genes and mutations between HR+ and HR– in HER2+ BC patients. In this retrospective cohort study, Joint HR and HER2 status distributions by more than ten specific clinic-pathological characteristics were evaluated by using Pearson’s chi-squared (χ2) test. The transciptome RNA-seqencing (RNA-seq) expression data together with detailed clinic-pathological information of HER2+ BC were from The Cancer Genome Atlas (TCGA) and UCSC Xena. 30,482 (71.02%) patients were identified as HR+ /HER2+ BC and 12,440 (28.98%) patients were identified as HR−/ HER2+ BC. HR+ /HER2+ BC patients were more likely to be younger than 50-year-old, white and infiltrating lobular carcinoma history than patients with HR−/HER2+ . Patients with HR+ /HER2+ BC had lower risks of breast cancer-specific death and higher overall survival rates. Mast cells were enriched in the HR+ /HER2+ BC group, while plasma cells were more abundant in the HR–/HER2+ BC group.In conclusion, HER2+ BC patients benefit differently from current HER2-directed therapies, maybe partly due to the HR status and gene mutations, and they may provide potentially prognostic and predictive value and new treatment strategies for clinicians. Keywords HR status · HER2 positive · Breast cancer · Clinical characteristics · Prognostic factors | Liang Shi, Pei-Wen Xi and Zhi Li have contributed equally to this | | --- | | Handling editor: V. Bolshakov. | 􀀍 Liang Shi [shiliang@njmu.edu.cn](shiliang@njmu.edu.cn) 􀀍 Lei Zhang [njsfyzl@163.com](njsfyzl@163.com) Pei-Wen Xi[xipeiwen@njmu.edu.cn](xipeiwen@njmu.edu.cn)[ ](xipeiwen@njmu.edu.cn)Zhi Li [drlz2018@njmu.edu.cn](drlz2018@njmu.edu.cn) Jing Wu [wuj_425@163.com](wuj_425@163.com)[ ](wuj_425@163.com)Xu Zhang [zhangxu2017@njmu.edu.cn](zhangxu2017@njmu.edu.cn) work. 1 Breast Disease Center, The First Affiliated Hospital With Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China 2 Health Management Center, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China 3 Department of Breast and Thyroid Surgery, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, China 4 Department of Pathology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China 5 Department of Gynaecology, Women’s Hospital of Nanjing Medical University (Nanjing Women and Children’s Healthcare Hospital), 123 Tianfei Xiang, Mochou Road, Nanjing 210004, China 1 3 Introduction Breast cancer (BC) has become the common prevalent cancer globally and one of the leading causes of cancer-related deaths in women (Sung et al. 2021) . It is acknowledged that BC is a heterogeneous disorder with different molecular subtypes and unique biological characteristics (Eroleset al. 2012) . Besides, there are diverse clinical treatmentsand outcomes specific to different molecular subtypes in BC patients. According to the 13th St. Gallen International Breast Cancer Conference, the molecul

FAQs

What question does the study address in HER2-positive breast cancer?

It assesses how clinical characteristics and potentially prognostic factors differ between HR+ and HR− groups within HER2-positive breast cancer patients.

Which databases and data sources were used for the analysis?

SEER Plus Database was used for HR and HER2 status across 2000–2019 cases, while transcriptome RNA-seq expression data came from TCGA and UCSC Xena.

What survival and immune-cell pattern differences were reported between HR+ /HER2+ and HR−/HER2+ patients?

HR+ /HER2+ patients had lower risk of breast cancer-specific death and higher overall survival; mast cells were enriched in HR+ /HER2+ while plasma cells were more abundant in HR−/HER2+.

Sep 30, 2026

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