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Clinicopathological features and prognostic analysis of HER2 low and fibrotic focus in HER2-negative breast cancer

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Abstract

Objective

The aim of this study is to evaluate the clinicopathological features and prognostic significance of HER2 low, fibrotic focus (FF), and tumor-infiltrating lymphocytes (TILs) in patients with HER2-negative breast cancer.

Methods

We retrospectively reviewed the data of 293 patients with HER2-negative, stage I–II, invasive breast cancer of non-specific types. The HER2-negative cases were classified into HER2 low and HER2 0. Digital analysis of hematoxylin–eosin stained whole slide images was used to evaluate the FF expression. TILs were also evaluated using the Whole Slide Image. Furthermore, the association between HER2 low, FF, and TILs as well as their prognostic significance were analyzed.

Results

The study cohort included 178 cases (60.8%) with HER2 low and 115 cases (39.2%) with HER2 0. Older age, lower Nottingham histological grade (NHG), estrogen receptor (ER) positivity, progesterone receptor (PR) positivity, and hormone receptor (HR) positivity were all associated with HER2 low. FF was correlated with older age, intermediate and low NHG, vascular invasion, HR positivity, HER2 low status, high Ki67 expression, and low TILs. Univariate survival analysis showed that FF was significantly associated with shorter progression-free survival (PFS). Stratified analysis indicated that in the HR-negative and HR-positive groups, HER2 status and TILs did not affect PFS. DFS was longer in patients without FF compared to those with FF in the HR-positive (hazard ratio [HR] = 0.313) and HER2 low (HR = 0.272) groups. DFS was also significantly longer in patients without FF compared to those with FF in the HR-negative (HR = 0.069) and HER2 0 groups (HR = 0.129).

Conclusion

The results indicated that the HER2 low status and the TILs expression did not impact prognosis. However, patients with FF exhibited distinct biological characteristics and prognostic significance, particularly in the HR-negative and HER2 0 groups. This provides a rationale for accurate diagnosis and treatment of HER2-negative breast cancer.

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Data availability

The datasets used and analyzed in this study are available from the corresponding author upon reasonable request.

Abbreviations

IHC:

Immunohistochemistry

ISH:

In situ hybridization

FF:

Fibroblastic focus

TILs:

Tumor-infiltrating lymphocytes

NHG:

Nottingham histological grade

ER:

Estrogen receptor

PR:

Progesterone receptor

HR:

Hormone Receptor

HE:

Hematoxylin–eosin

ADC:

Antibody–drug conjugates

PFS:

Progression-free survival

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Author notes

  1. Meng Yue and Si Wu have contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang, 050011, Hebei, China

    Meng Yue, Si Wu, Chang Liu, Lijing Cai, Xinran Wang, Ying Jia, Dandan Han & Yueping Liu

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  1. Meng Yue
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  2. Si Wu
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  3. Chang Liu
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  4. Lijing Cai
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  8. Yueping Liu
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Contributions

MY and SW contributed toward conceptualization, methodology, investigation, data curation, and writing-original draft preparation; CL and LC contributed toward investigation, and data curation; XW contributed toward investigation, and data curation; YJ and DH contributed toward investigation; and YL contributed toward writing-reviewing and editing.

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Correspondence to Yueping Liu.

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Yue, M., Wu, S., Liu, C. et al. Clinicopathological features and prognostic analysis of HER2 low and fibrotic focus in HER2-negative breast cancer. Breast Cancer Res Treat 203, 373–381 (2024). https://doi.org/10.1007/s10549-023-07103-x

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  • DOI: https://doi.org/10.1007/s10549-023-07103-x

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