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Clinicopathological differences and survival benefit in ER+/PR+/HER2+ vs ER+/PR−/HER2+ breast cancer subtypes

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Abstract

Introduction

Breast cancer subtypes based on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression have significant implications for prognosis. HER2-positive tumors historically demonstrated poorer survival, but anti-HER2 targeted therapy improved outcomes. However, hormone receptor (HR)-positive patients may experience reduced benefit due to HER2-HR signaling crosstalk.

Methods

Data from two databases, the Shanghai Jiao Tong University Breast Cancer Data Base (SJTUBCDB) and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database, were analyzed. Propensity score adjustments were used to balance patient characteristics between ER+/PR+/HER2+ and ER+/PR−/HER2+ subtypes. Kaplan–Meier survival curves estimated disease-free survival (DFS), breast cancer-specific survival (BCSS), overall survival (OS) for these subtypes in the SJTUBCDB, while subgroup analyses using multivariable models were performed based on menstruation, pN stage, HER2-targeted therapy, and endocrinotherapy.

Results

The ER+/PR+/HER2+ group showed significantly better DFS and BCSS than the ER+/PR−/HER2+ group, particularly in postmenopausal and pN0 stage patients. Survival outcomes were similar after anti-HER2 therapy or endocrine aromatase inhibitor (AI) therapy in both groups. However, among patients receiving selective estrogen receptor modulator (SERM) treatment, those in the ER+/PR−/HER2+ group had a significantly worse prognosis compared to ER+/PR+/HER2+ patients.

Conclusions

HER2-positive breast cancers with different HR statuses exhibit distinct clinicopathological features and survival outcomes. Patients in the ER+/PR+/HER2+ group generally experience better survival, particularly in postmenopausal and pN0 stage patients. Treatment strategies should consider HR status and specific modalities for better personalized management.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

SJTUBCDB:

Shanghai Jiao Tong University Breast Cancer Data Base

SEER:

Surveillance, Epidemiology, and End Results

IPTW:

Inverse probability of treatment weighting

HR:

Hormone receptor

ER:

Estrogen-receptor

PR:

Progesterone receptor

HER2:

Human epidermal growth factor receptor-2

FISH:

Fluorescence in situ hybridization

SISH:

Silver in situ hybridization

IDC:

Invasive ductal carcinoma

ILC:

Invasive lobular carcinoma

BCSS:

Breast cancer-specific survival

OS:

Overall survival

DFS:

Disease-free survival

SEER:

Surveillance Epidemiology and End Results

HRs:

Hazard ratios

CI:

Confidence interval

SERM:

Selective estrogen receptor modulator

AI:

Aromatase inhibitor

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Funding

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Author information

Author notes

  1. Wu Ding and Dengfeng Ye contributed equally to this work and should be considered as co-first authors.

Authors and Affiliations

  1. Department of Oncological Surgery, Shaoxing Second Hospital, Shaoxing, 312000, China

    Wu Ding, Dengfeng Ye, Haifeng Chen & Zhian Li

  2. Department of Early Childhood Education, Shaoxing Vocational and Technical College, Shaoxing, China

    Yingli Lin

  3. Department of Clinical Medicine, Shaoxing University School of Medicine, Shaoxing, China

    Wu Ding

  4. Department of Surgery, Shaoxing Second Hospital, Shaoxing, 312000, China

    Chuanjian Tu

Authors
  1. Wu Ding
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  2. Dengfeng Ye
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  3. Haifeng Chen
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  4. Yingli Lin
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  5. Zhian Li
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  6. Chuanjian Tu
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Contributions

Conception and design: WD, DY, HC, CT. Administrative support: YL, ZL. Collection and assembly of data: WD, YL, ZL. Data analysis and interpretation: WD, DY, HC. Manuscript writing: all authors. Final approval of manuscript: All authors.

Corresponding authors

Correspondence to Zhian Li or Chuanjian Tu.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Our study was approved by the independent ethics committee/institutional review board at Shaoxing Second Hospital Ethical Committee. The data from the SEER datasets are publicly available and therefore do not require informed patient consent.

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Ding, W., Ye, D., Chen, H. et al. Clinicopathological differences and survival benefit in ER+/PR+/HER2+ vs ER+/PR−/HER2+ breast cancer subtypes. Breast Cancer 31, 295–304 (2024). https://doi.org/10.1007/s12282-023-01538-2

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  • DOI: https://doi.org/10.1007/s12282-023-01538-2

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