Persistence of AKT1 low quiescent cancer cells after neoadjuvant chemotherapy in triple negative breast cancer patients.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11579-11579
Author(s):  
Sheheryar Kairas Kabraji ◽  
Xavier Sole ◽  
Ying Huang ◽  
Clyde Bango ◽  
Michaela Bowden ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Immunofluorescence Microscopy ◽  
Chemotherapy Resistance ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Quantitative Immunofluorescence

11579 Background: The mechanisms that allow triple negative breast cancer (TNBC) tumors to survive neoadjuvant chemotherapy (NACT) are incompletely understood. Evidence suggests that proliferative heterogeneity may contribute to primary chemotherapy resistance in patients with localized triple negative breast cancer. However, the detailed characterization of a drug-resistant cancer cell state in residual TNBC tissue after NACT has remained elusive. AKT1lowquiescent cancer cells (QCCs) are a quiescent, epigenetically plastic, and chemotherapy resistant subpopulation initially identified in experimental cancer models. Here, we asked whether AKT1low QCCs actually exist in primary tumors from patients with TNBC and persist after treatment with NACT. Methods: We identified QCCs in primary and metastatic human breast tumors using automated, quantitative, immunofluorescence microscopy coupled with computational and statistical analysis. We obtained pre-treatment biopsy, post-treatment mastectomy, and metastatic specimens from a retrospective cohort of TNBC patients treated with neoadjuvant chemotherapy at Massachusetts General Hospital (n = 25). Using automated quantitative immunofluorescence microscopy, QCCs were identified as AKTlow / H3K9me2low / HES1high cancer cells using prespecified immunofluorescence intensity thresholds. QCCs were represented as 2D and 3D digital tumor maps and QCC percentage (QCC-P) and QCC cluster index (QCC-CI) were determined for each sample. Results: We found that QCCs exist as non-random and heterogeneously distributed clusters within primary tumors. In addition, these QCC clusters are enriched after treatment with multi-agent, multi-cycle, neoadjuvant chemotherapy in both residual primary tumors as well as nodal and distant metastases in patients with triple negative breast cancer. Conclusions: Together, these data qualify QCCs as a non-genetic mechanism of chemotherapy resistance in triple negative breast cancer patients that warrants further study.

scholarly journals Abundance of Regulatory T Cell (Treg) as a Predictive Biomarker for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3038 ◽  
Author(s):  
Masanori Oshi ◽  
Mariko Asaoka ◽  
Yoshihisa Tokumaru ◽  
Fernando A. Angarita ◽  
Li Yan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cell ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Tumor Infiltrating Lymphocytes ◽  
Predictive Biomarker ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Cancer Aggressiveness

Regulatory CD4+ T cell (Treg), a subset of tumor-infiltrating lymphocytes (TILs), are known to suppress anticancer immunity but its clinical relevance in human breast cancer remains unclear. In this study, we estimated the relative abundance of Tregs in breast cancer of multiple patient cohorts by using the xCell algorithm on bulk tumor gene expression data. In total, 5177 breast cancer patients from five independent cohorts (TCGA-BRCA, GSE96058, GSE25066, GSE20194, and GSE110590) were analyzed. Treg abundance was not associated with cancer aggressiveness, patient survival, or immune activity markers, but it was lower in metastatic tumors when compared to matched primary tumors. Treg was associated with a high mutation rate of TP53 genes and copy number mutations as well as with increased tumor infiltration of M2 macrophages and decreased infiltration of T helper type 1 (Th1) cells. Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) was significantly associated with low Treg abundance in triple negative breast cancer (TNBC) but not in ER-positive/Her2-negative subtype. High Treg abundance was significantly associated with high tumor expression of multiple immune checkpoint inhibitor genes. In conclusion, Treg abundance may have potential as a predictive biomarker of pCR after NAC in TNBC.

scholarly journals DNAJC28 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of DnaJ (Hsp40) homolog, subfamily C, member 28, encoded by DNAJC28 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, DNAJC28 expression was correlated with overall survival in patients with breast cancer. DNAJC28 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals VPS52 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Free Survival ◽  
Significant Gene ◽  
Vacuolar Protein

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of vacuolar protein sorting 52, encoded by VPS52 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, VPS52 expression was correlated with recurrence-free survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. VPS52 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals MAP4K2 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Mitogen Activated Protein Kinase ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Mitogen Activated Protein ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of mitogen-activated protein kinase kinase kinase kinase 2, encoded by MAP4K2 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, MAP4K2 expression was correlated with distant metastasis-free survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. MAP4K2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals PAX5 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of paired box 5, encoded by PAX5 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, PAX5 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. PAX5 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals BACH2 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Leucine Zipper ◽  
Triple Negative ◽  
Breast Cancer Patients ◽  
Basic Leucine Zipper ◽  
Primary Tumors ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of BTB and CNC homology 1, basic leucine zipper transcription factor 2, encoded by BACH2 when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, BACH2 expression was correlated with overall survival in patients with breast cancer. BACH2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals GBP5 expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Significant Gene ◽  
Inflammasome Component ◽  
Guanylate Binding Protein

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival at time of analysis: dead or alive. The inflammasome component and guanylate-binding protein GBP5 emerged as among the most significant differences, transcriptome-wide, when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, GBP5 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. GBP5 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

scholarly journals PD-L2 (PDCD1LG2) expression associates with survival in triple negative breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Microarray Data ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Breast Cancer Patients ◽  
Primary Tumors ◽  
Programmed Cell Death 1 ◽  
Significant Gene

We mined published microarray data (1) to understand the most significant gene expression differences in the tumors of triple negative breast cancer patients based on survival following treatment: dead or alive. We observed significant transcriptome-wide differential expression of programmed cell death 1 ligand 2, encoded by PDCD1LG2, also known as PD-L2, when comparing the primary tumors of triple negative breast cancer patients dead or alive. Importantly, PD-L2 expression was significantly correlated with overall survival in basal subtype breast cancer, a molecular subtype sharing significant overlap with triple negative breast cancer. PD-L2 may be of relevance as a biomarker or as a molecule of interest in understanding the etiology or progression of triple negative breast cancer.

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