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Subclassifying triple-negative breast cancers and its potential clinical utility

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Abstract

The molecular subtyping of triple-negative breast cancer (TNBC) is critical to guiding individualized patient treatment. In this study, we sought to characterize the clinicopathologic features of TNBC subtypes and to identify correlates of patient survival in an effort to provide a robust foundation for treatment planning. We additionally assessed PD-L1 expression in Chinese TNBC patients and evaluated the relationship between such expression and immunotherapeutic treatment outcomes. Based on analyses of histologic characteristics including apocrine differentiation, tumor-infiltrating lymphocytes, and metaplastic features, we selected immunohistochemical (IHC) markers including CD8, FOXC1, and AR for use in classifying TNBC cases. Associations between these subtypes and a range of clinicopathologic characteristics were evaluated. We classified a cohort of 93 TNBC patients into individuals with luminal androgen receptor (LAR), immunomodulatory (IM), basal-like immune-suppressed (BLIS), and mesenchymal (MES) tumor subtypes (23, 24, 39, and 7 cases, respectively). PD-L1 positivity was observed in 49.6% of cases and was more common in individuals with IM subtype disease. Mismatch repair deficiency (dMMR) was observed in just one patient. Significant differences in histologic grade, pT stage, lymphocyte distribution patterns, large scarring areas without cells in tumor of central (central scar), and PD-L1, P53, and Rb status were observed among these TNBC subtypes, whereas no such differences were observed with respect to age, invasion pattern, or pN stage. Rates of disease progression were higher at the 40–50 month follow-up time point, but there were no significant differences in recurrence-free survival or breast cancer-specific survival among these subtypes. IHC markers associated with clinicopathologic characteristics represent a powerful approach to TNBC molecular typing, providing a foundation for precision patient treatment. PD-L1 expression may represent a relevant factor in TNBC patient immunotherapeutic treatment planning, whereas dMMR is not likely to be of substantial value when evaluating immunotherapeutic efficacy in these patients.

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Funding

This study was supported by grants from the Shanxi Provincial Health Commission (2020065) and the Institute Research Foundation of Shanxi Cancer Hospital (0200189).

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Author notes

  1. Ke-Ming Yun and Yan-Feng Xi contributed equally to this work

Authors and Affiliations

  1. Department of Pathology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China

    Jing Lian, Hai-xia Ma, En-Wei Xu, Peng Bu & Yan-Feng Xi

  2. Institute of Forensic Medicine, Shanxi Medical University, Taiyuan, Shanxi Province, People’s Republic of China

    Ke-Ming Yun

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  1. Jing Lian
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  2. Hai-xia Ma
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Contributions

Jing Lian, Ke-MingYun, and Yan-Feng Xi identified cases of interest and designed the study. Jing Lian and Peng Bu carried out the studies. Jing Lian and Hai-Xia Ma collected data and performed the statistical analysis. Jing Lian and Li-Xia Wang produced the initial draft of the manuscript. Jing Lian, Ke-Ming Yun, and Yan-Feng Xi contributed to the revision of the manuscript. All authors participated in writing, editing, and reviewing the manuscript and gave final approval for publication. Jing Lian takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding authors

Correspondence to Ke-Ming Yun or Yan-Feng Xi.

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Ethics approval

Material and patient date used in this study were provided by the Shanxi Cancer Hospital. The study was approved by the institutional review board of the ethical committee at the Shanxi Cancer Hospital, according to the Declaration of Helsinki (Approval Number: 2019075).

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All authors have declared that no conflict of interest exists.

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Lian, J., Ma, Hx., Xu, EW. et al. Subclassifying triple-negative breast cancers and its potential clinical utility. Virchows Arch 481, 13–21 (2022). https://doi.org/10.1007/s00428-022-03329-0

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