A triple-negative breast cancer surrogate subtype classification that correlates with gene expression subtypes

Yoo, Tae-Kyung; Kang, Jun; Lee, Awon; Chae, Byung Joo

doi:10.1007/s10549-021-06437-8

Cited by 7 publications

(5 citation statements)

References 52 publications

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“…IHC-MES was the second most common subtype, and numerically, it was associated with worse mDFS and mOS, which is consistent with the findings in the literature [ 13 , 14 , 15 ]. Unfortunately, the benefit of conventional adjuvant systemic treatment for this subtype is often poor, if any, given its specific molecular characteristics, which has motivated researchers to consider regimens mimicking sarcomatous disease [ 24 ].…”

Section: Discussionsupporting

confidence: 91%

“…Our study demonstrated a low percentage of unclassifiable (2.2%) and IHC-mixed (11.4%) compared to the other studies mentioned in Table 1 . In a study conducted by Yoo in 2022, the majority of patients with IHC-unclassifiable had presented with mesenchymal subtype on genomic classification [ 15 ]. Interestingly, Zhao et al, Leeha et al, and Hu et al did not report mixed subtypes by using their IHC panels [ 14 , 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemistry (IHC) is an established laboratory method for evaluating the presence of antigens that is widely used in breast cancer and is pivotal for tailoring systemic treatments (e.g., the human epidermal growth factor receptor 2—HER2) [ 10 ]. Moreover, IHC is significantly less expensive and laborious than gene expression and has been evaluated in several studies as a surrogate marker of established intrinsic genomic-based subtyping assays, as summarized in Table 1 [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. Although some studies have provided survival data amongst the subtypes, the effect of chemotherapy on the pathological complete response, and if it serves as surrogate biomarker of survival, has not been reported.…”

Section: Introductionmentioning

confidence: 99%

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Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

Paula,

Crocamo,

de Sousa

et al. 2024

IJMS

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The intrinsic subtype of triple-negative breast cancer (TNBC) is based on genomic evaluation. In this study, we report the survival and pathological complete response (pCR) rates of TNBC patients subtyped by IHC and treated with neoadjuvant chemotherapy (NACT). A retrospective cohort of 187 TNBC patients who received NACT between 2008 and 2017 was used, and IHC subtyping was performed on biopsy specimens before chemotherapy. The subtyping revealed predominantly basal-like tumors (IHC-BL, 61%), followed by basal-like immune-suppressed tumors (IHC-BLIS, 31%), mesenchymal tumors (12.5%), luminal androgen receptor tumors (IHC-LAR, 12%), and basal-like immune-activated tumors (IHC-BLIA, 10.9%). The pCR rate varied among subtypes, with IHC-BLIA showing the highest (30.0%) and IHC-LAR showing the lowest (4.5%). IHC-BLIS led in recurrence sites. Overall and disease-free survival analyses did not show significant differences among subtypes, although IHC-BLIA demonstrated a trend toward better survival, and IHC-mesenchymal, worse. Patients who achieved pCR exhibited significantly better disease-free survival and overall survival than non-responders. This study underscores the potential of IHC-based subtyping in TNBC management, highlighting distinct response patterns to neoadjuvant chemotherapy and potential implications for treatment strategies. Further research is warranted to validate these findings and explore tailored therapeutic approaches for specific TNBC subtypes.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

Paula,

Crocamo,

de Sousa

et al. 2024

IJMS

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“… 30 , 31 Potential treatments for the IM subtype include programmed cell death protein 1 (PD-1), programmed death ligand 1 (PD-L1), and other immune checkpoint inhibitors. 32 , 33 Expression of PD-L1 in tumor cells or its presence in the tumor microenvironment indicates high levels of tumor-infiltrating lymphocytes and positively correlates with the triple-negative status in breast cancer. 34 Anti-AR medication is a possible treatment option for the LAR subtype.…”

Section: Introductionmentioning

confidence: 99%

Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review

Natarajan

Raghavendran

et al. 2023

Technol Cancer Res Treat

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Breast cancer is the most common malignancy and the second most common cause of cancer-related mortality in women. Triple-negative breast cancers do not express estrogen receptors, progesterone receptors, or human epidermal growth factor receptor 2 and have a higher recurrence rate, greater metastatic potential, and lower overall survival rate than those of other breast cancers. Treatment of triple-negative breast cancer is challenging; molecular-targeted therapies are largely ineffective and there is no standard treatment. In this review, we evaluate current attempts to classify triple-negative breast cancers based on their molecular features. We also describe promising treatment methods with different advantages and discuss genetic biomarkers and other prediction tools. Accurate molecular classification of triple-negative breast cancers is critical for patient risk categorization, treatment decisions, and surveillance. This review offers new ideas for more effective treatment of triple-negative breast cancer and identifies novel targets for drug development.

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“…These subtypes were called the Vanderbilt TNBC subtypes, consisting of basal-like 1 and 2 (BL1, BL2), luminal androgen receptor (LAR), mesenchymal (M), mesenchymal stem-like (MSL), and immunomodulatory (IM). Since then, several research groups have further validated these subtypes and narrowed them down to four major types (BL1, BL2, LAR, M) ( Burstein et al, 2015 ; Lehmann et al, 2021 ; Wang et al, 2019 ; Yin et al, 2020 ; Yoo et al, 2022 ). Other follow-up studies also reported several new subclasses for TNBC classification ( Burstein et al, 2015 ; Ensenyat-Mendez et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Retrospective study of transcriptomic profiling identifies Thai triple-negative breast cancer patients who may benefit from immune checkpoint and PARP inhibitors

Suntiparpluacha,

Chanthercrob,

Sa-nguanraksa

et al. 2023

PeerJ

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Background Triple-negative breast cancer (TNBC) is a rare and aggressive breast cancer subtype. Unlike the estrogen receptor-positive subtype, whose recurrence risk can be predicted by gene expression-based signature, TNBC is more heterogeneous, with diverse drug sensitivity levels to standard regimens. This study explored the benefit of gene expression-based profiling for classifying the molecular subtypes of Thai TNBC patients. Methods The nCounter-based Breast 360 gene expression was used to classify Thai TNBC retrospective cohort subgroups. Their expression profiles were then compared against the previously established TNBC classification system. The differential characteristics of the tumor microenvironment and DNA damage repair signatures across subgroups were also explored. Results Thai TNBC cohort could be classified into four main subgroups, corresponding to the LAR, BL-2, and M subtypes based on Lehmann’s TNBC classification. The PAM50 gene set classified most samples as basal-like subtypes except for Group 1. Group 1 exhibited similar enrichment of the metabolic and hormone response pathways to the LAR subtype. Group 2 shared pathway activation with the BL-2 subtype. Group 3 showed an increase in the EMT pathway, similar to the M subtype. Group 4 showed no correlation with Lehmann’s TNBC. The tumor microenvironment (TME) analysis showed high TME cell abundance with increased expression of immune blockade genes in Group 2. Group 4 exhibited low TME cell abundance and reduced immune blockade gene expressions. We also observed distinct signatures of the DNA double-strand break repair genes in Group 1. Conclusions Our study reported unique characteristics between the four TNBC subgroups and showed the potential use of immune checkpoint and PARP inhibitors in subsets of Thai TNBC patients. Our findings warrant further clinical investigation to validate TNBC’s sensitivity to these regimens.

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A triple-negative breast cancer surrogate subtype classification that correlates with gene expression subtypes

Cited by 7 publications

References 52 publications

Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

Triple-Negative Breast Cancer Subclassified by Immunohistochemistry: Correlation with Clinical and Pathological Outcomes in Patients Receiving Neoadjuvant Chemotherapy

Molecular Classification, Treatment, and Genetic Biomarkers in Triple-Negative Breast Cancer: A Review

Retrospective study of transcriptomic profiling identifies Thai triple-negative breast cancer patients who may benefit from immune checkpoint and PARP inhibitors

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