Deep learning and manual assessment show that the absolute mitotic count does not contain prognostic information in triple negative breast cancer

Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.

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Multiplexed imaging analysis of the tumor-immune microenvironment reveals predictors of outcome in triple-negative breast cancer

Communications Biology ◽

10.1038/s42003-021-02361-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Aalok Patwa ◽

Rikiya Yamashita ◽

Jin Long ◽

Tyler Risom ◽

Michael Angelo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ion Beam ◽

Breast Cancer Subtype ◽

Tissue Imaging ◽

Immune Microenvironment ◽

Prognostic Information ◽

Tumor Immune Microenvironment ◽

Prior Literature

AbstractTriple-negative breast cancer, the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification and treatment management. Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion beam imaging that produces interpretable results, and is generalizable to other cancer types.

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Gancochlearols E − I, meroterpenoids from Ganoderma cochlear against COX-2 and triple negative breast cancer cells and the absolute configuration assignment of ganomycin K

Bioorganic Chemistry ◽

10.1016/j.bioorg.2021.104706 ◽

2021 ◽

Vol 109 ◽

pp. 104706

Author(s):

Yan-Peng Li ◽

Xiao-Ting Jiang ◽

Fu-Ying Qin ◽

Hao-Xing Zhang ◽

Yong-Xian Cheng

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Triple Negative Breast Cancer ◽

Absolute Configuration ◽

Breast Cancer Cells ◽

Triple Negative ◽

Configuration Assignment ◽

Cox 2 ◽

The Absolute

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Predicting Relapse in Patients With Triple Negative Breast Cancer (TNBC) Using a Deep-Learning Approach

Frontiers in Physiology ◽

10.3389/fphys.2020.511071 ◽

2020 ◽

Vol 11 ◽

Author(s):

Guangyuan Yu ◽

Xuefei Li ◽

Ting-Fang He ◽

Tina Gruosso ◽

Dongmei Zuo ◽

...

Keyword(s):

Breast Cancer ◽

Deep Learning ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Learning Approach

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Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer

10.21203/rs.3.rs-132431/v1 ◽

2021 ◽

Author(s):

Aalok Patwa ◽

Rikiya Yamashita ◽

Jin Long ◽

Leeat Keren ◽

Michael R. Angelo ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ion Beam ◽

Breast Cancer Subtype ◽

Beta Catenin ◽

Computational Pipeline ◽

Immune Microenvironment ◽

Prognostic Information ◽

Tumor Immune Microenvironment

Abstract Triple-negative breast cancer (TNBC), the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification, treatment management, and immunotherapies. Prior literature has shown that interrogation of the tumor-immune microenvironment (TIME) may be a promising approach for the discovery of novel biomarkers that can fill these gaps. Recent developments in high-dimensional tissue imaging technology, such as multiplexed ion beam imaging (MIBI), provide spatial context to protein expression in the TIME, opening doors for in-depth characterization of cellular processes. We developed a computational pipeline for the robust examination of the TIME using MIBI. We discover that profiling the functional proteins involved in cell-to-cell interactions in the TIME predicts recurrence and overall survival in TNBC. The interactions between CD45RO and Beta Catenin and CD45RO and HLA-DR were the most relevant for patient stratification. We demonstrated the clinical relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying their interactions to recurrence and survival. Multivariate analysis revealed that our methods provide additional prognostic information compared to clinical variables. Our novel computational pipeline produces interpretable results, and is generalizable to other cancer types.

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Ki67 Index Changes and Tumor-Infiltrating Lymphocyte Levels Impact the Prognosis of Triple-Negative Breast Cancer Patients With Residual Disease After Neoadjuvant Chemotherapy

Frontiers in Oncology ◽

10.3389/fonc.2021.668610 ◽

2021 ◽

Vol 11 ◽

Author(s):

Yihua Wang ◽

Beige Zong ◽

Yu Yu ◽

Yu Wang ◽

Zhenrong Tang ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Residual Disease ◽

Prognostic Significance ◽

Ki67 Index ◽

Breast Cancer Patients ◽

Prognostic Information ◽

Index Changes

PurposeThe aim of this study was to assess the prognostic influence of Ki67 index changes in patients with primary triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy (NAC), and to evaluate whether the combination of Ki67 index changes and residual disease (RD) tumor-infiltrating lymphocytes (TILs) provides additional prognostic information for this group.Materials and MethodsData from 109 patients with primary TNBC and RD after NAC were analyzed retrospectively. Ki67 changes and RD TIL levels were investigated for associations with recurrence-free survival (RFS) and overall survival (OS) using Kaplan–Meier and Cox analyses.ResultsKi67 index decreased after NAC in 53 patients (48.6%) and high RD TIL levels (≥30%) were observed in 54 patients (49.5%). In multivariate Cox analyses, no Ki67 decrease status and low RD TIL levels were significantly associated with reduced RFS (hazard ratio (HR): 2.038, 95% confidence interval (CI): 1.135–3.658, P = 0.017; HR: 2.493, 95% CI: 1.335–4.653, P = 0.004), and OS (HR: 2.187, 95% CI: 1.173–4.077, P = 0.014; HR: 2.499, 95% CI: 1.285–4.858, P = 0.007), respectively. Notably, low RD TIL levels were significantly associated with reduced RFS (HR: 3.567, 95% CI: 1.475–8.624, P = 0.005) and reduced OS (HR: 3.873, 95% CI: 1.512–9.918, P = 0.005) in only the no Ki67 decrease group. The differences in 3-year RFS and OS between patients with no Ki67 decrease and low or high RD TIL levels were 24.4% vs 79.1% (P = 0.0001) and 33.1% vs 87.5% (P = 0.0001), respectively.ConclusionKi67 index changes and RD TIL levels were associated with the prognosis of patients with primary TNBC with RD after NAC. RD TIL levels had greater prognostic significance in the no Ki67 decrease group.

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