A Retrospective Exploratory Analysis for Serum Extracellular Vesicles Reveals APRIL (TNFSF13), CXCL13, and VEGF-A as Prognostic Biomarkers for Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Neoadjuvant chemotherapy (NAC) is widely used as a standard treatment for early-stage triple-negative breast cancer (TNBC). While patients who achieve pathologic complete response (pCR) have a highly favorable outcome, patients who do not achieve pCR have variable prognoses. It is important to identify patients who are most likely to have poor survival outcomes to identify candidates for more aggressive therapeutic approaches after NAC.

Genomic characteristics of triple negative apocrine carcinoma: a comparison to triple negative breast cancer.

Apocrine carcinoma is a rare breast cancer subtype. As such, the genomic characteristics of apocrine carcinoma with triple negative immunohistochemical results (TNAC), which has been treated as triple negative breast cancer (TNBC), have not been revealed. In this study, we evaluated the genomic characteristics of TNAC compared to TNBC with low Ki-67 (LK-TNBC).

Elevated Level of Nerve Growth Factor (NGF) in Serum-Derived Exosomes Predicts Poor Survival in Patients with Breast Cancer Undergoing Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) is a standard treatment strategy for patients with locally advanced breast cancer (LABC). However, there are no established predictors of chemosensitivity and survival in LABC patients who undergo NAC. Many studies have demonstrated that exosomes and cytokines are important players in intercellular communication between tumors and their environments, and are involved in chemotherapy resistance.

Cytokine profiling in serum-derived exosomes isolated by different methods.

Exosomes in blood play an important role in cell-to-cell signaling and are a novel source of biomarkers for the diagnosis and prognosis of diseases. Recently, evidence has accumulated that cytokines are released from encapsulated exosomes and are capable of eliciting biological effects upon contact with sensitive cells. However, there is currently limited information on exosome isolation methods for cytokine research.

Prognostication of a 13-immune-related-gene signature in patients with early triple-negative breast cancer.

Purpose: We investigated the expression profiles of immune genes in patients with triple-negative breast cancer (TNBC) to identify the prognostic value of immune genes and their clinical implications.

Methods: NanoString nCounter Analysis of 770 immune-related genes was used to measure immune gene expression in patients with TNBC who underwent curative surgery followed by adjuvant chemotherapy at Samsung Medical Center between 2000 and 2004. Statistical analyses were conducted to identify the associations between gene expression and distant recurrence-free survival (DRFS).

Molecular alterations and poziotinib efficacy, a pan-HER inhibitor, in human epidermal growth factor receptor 2 (HER2)-positive breast cancers: Combined exploratory biomarker analysis from a phase II clinical trial of poziotinib for refractory HER2-positive breast cancer patients.

We aimed to investigate the impact of genetic alterations on the efficacy of poziotinib in a phase II clinical trial of patients with heavily treated HER2-positive metastatic breast cancer (BC). We performed targeted ultra-deep sequencing with a customized cancer gene panel and RNA expression assay using BC specimens. Of 106 patients, biomarker data were available for 85.

Validation of the new AJCC eighth edition of the TNM classification for breast cancer with a single-center breast cancer cohort.

Purpose: The new eighth edition TNM classification by the AJCC for breast cancer (BC) incorporates biologic factors and gene expression prognostic panels, in addition to traditional anatomic factors. In this study, we evaluated the prognostic value of this new staging system compared to the previous AJCC 7th edition staging system.

Methods: We conducted a retrospective analysis of women with stage I, II, or III BC who underwent curative surgery with/without adjuvant systemic therapy at Samsung Medical Center between July 2004 and December 2008.

Circulating tumor DNA shows variable clonal response of breast cancer during neoadjuvant chemotherapy.

Circulating tumor DNA (ctDNA) correlates with tumor burden and provides early detection of treatment response and tumor genetic alterations in breast cancer (BC). In this study, we aimed to identify genetic alterations during the process of tumor clonal evolution and examine if ctDNA level well indicated clinical response to neoadjuvant chemotherapy (NAC) and BC recurrence. We performed targeted ultra-deep sequencing of plasma DNAs, matched germline DNAs and tumor DNAs from locally advanced BC patients.

Immune signature of metastatic breast cancer: Identifying predictive markers of immunotherapy response.

In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens.

Clinical implications of genomic profiles in metastatic breast cancer with a focus on TP53 and PIK3CA, the most frequently mutated genes.

Breast cancer (BC) has been genetically profiled through large-scale genome analyses. However, the role and clinical implications of genetic alterations in metastatic BC (MBC) have not been evaluated. Therefore, we conducted whole-exome sequencing (WES) and RNA-Seq of 37 MBC samples and targeted deep sequencing of another 29 MBCs.

The effect of androgen receptor expression on clinical characterization of metastatic breast cancer.

In breast cancer (BC), androgen receptor (AR) expression is related to estrogen receptor (ER) and/or progesterone receptor (PgR) expression. AR expression is an indicator of good prognosis in breast cancer regardless of hormone receptor (HR) status. In this study, we evaluated the effect of AR-related gene expression on clinical characterization of metastatic BC.

Association between Mutation and Expression of as a Potential Prognostic Marker of Triple-Negative Breast Cancer.

Purpose: , the most frequently mutated gene in breast cancer, is more frequently altered in HER2-enriched and basal-like breast cancer. However, no studies have clarified the role of status as a prognostic and predictive marker of triple-negative breast cancer (TNBC).

Materials And Methods: We performed p53 immunohistochemistry (IHC), nCounter mRNA expression assay, and DNA sequencing to determine the relationship between alteration and clinical outcomes of TNBC patients.

Statins affect ETS1-overexpressing triple-negative breast cancer cells by restoring DUSP4 deficiency.

We investigated the molecular mechanisms underlying statin-induced growth suppression of triple-negative breast cancer (TNBC) that overexpress the transcription factor ets proto-oncogene 1(ets-1) and downregulate dual specific protein phosphatase 4(dusp4) expression. We examined the gene expression of BC cell lines using the nCounter expression assay, MTT viability assay, cell proliferation assay and Western blot to evaluate the effects of simvastatin. Finally, we performed cell viability testing in TNBC cell line-transfected DUSP4.

The relationship between nuclear factor (NF)-κB family gene expression and prognosis in triple-negative breast cancer (TNBC) patients receiving adjuvant doxorubicin treatment.

We investigated gene expression profiles of the NF-κB pathway in patients with triple-negative breast cancer (TNBC) receiving adjuvant chemotherapy to determine the prognostic value of NF-κB pathway genes according to chemotherapeutic regimen. We used the nCounter expression assay to measure expression of 11 genes (NFKB1, NFKB2, RELA, RELB, REL, TP53, FOXC1, TBP, SP1, STAT3 and IRF1 genes) belonging to the NF-κB pathway using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Of the 203 patients, 116 were treated with a chemotherapeutic regimen containing doxorubicin.

Gene Expression Profiling of Breast Cancer Brain Metastasis.

The biology of breast cancer brain metastasis (BCBM) is poorly understood. We aimed to explore genes that are implicated in the process of brain metastasis of primary breast cancer (BC). NanoString nCounter Analysis covering 252 target genes was used for comparison of gene expression levels between 20 primary BCs that relapsed to brain and 41 BCBM samples.

Prognostic value of ERBB4 expression in patients with triple negative breast cancer.

Background: Triple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis. Epidermal growth factor receptor (EGFR) overexpression in TNBC indicates poor prognosis. However, there is no previous study of the relationship between expression of the entire human epidermal growth factor receptor (HER) family genes and patient prognosis in TNBC.

Mutational profiling of brain metastasis from breast cancer: matched pair analysis of targeted sequencing between brain metastasis and primary breast cancer.

Although breast cancer is the second most common cause of brain metastasis with a notable increase of incidence, genes that mediate breast cancer brain metastasis (BCBM) are not fully understood. To study the molecular nature of brain metastasis, we performed gene expression profiling of brain metastasis and matched primary breast cancer (BC). We used the Ion AmpliSeq Cancer Panel v2 covering 2,855 mutations from 50 cancer genes to analyze 18 primary BC and 42 BCBM including 15 matched pairs.

Role of HER2 mutations in refractory metastatic breast cancers: targeted sequencing results in patients with refractory breast cancer.

In women with metastatic breast cancer (MBC), introduction of the anti-HER2 (human epidermal growth factor receptor-2) directed therapies including trastuzumab, pertuzumab, lapatinib, and/or trastuzumab-DM1 has markedly improved overall survival. However, not all cases of HER2-positive breast tumours derive similar benefit from HER2-directed therapy, and a significant number of patients experience disease progression because of primary or acquired resistance to anti-HER2-directed therapies. We integrated genomic and clinicopathological analyses in a cohort of patients with refractory breast cancer to anti-HER2 therapies to identify the molecular basis for clinical heterogeneity.

Molecular characterization of patients with pathologic complete response or early failure after neoadjuvant chemotherapy for locally advanced breast cancer using next generation sequencing and nCounter assay.

Neoadjuvant chemotherapy (NAC) has the added advantage of increasing breast conservation rates with equivalent survival outcomes compared with adjuvant chemotherapy. A subset of breast cancer patients who received NAC experienced early failure (EF) during the course of therapy or within a short period after curative breast surgery. In contrast, patients with pathological complete response (pCR) were reported to have markedly favorable outcomes.

A seven-gene signature can predict distant recurrence in patients with triple-negative breast cancers who receive adjuvant chemotherapy following surgery.

The aim of this study was to investigate candidate genes that might function as biomarkers to differentiate triple negative breast cancers (TNBCs) among patients, who received adjuvant chemotherapy after curative surgery. We tested whether the results of a NanoString expression assay that targeted 250 prospectively selected genes and used mRNA extracted from formalin-fixed, paraffin-embedded would predict distant recurrence in patients with TNBC. The levels of expression of seven genes were used in a prospectively defined algorithm to allocate each patient to a risk group (low or high).

Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway.

Primary TNBCs are treated as if they were a single disease entity, yet it is clear they do not behave as a single entity in response to current therapies. Recently, we reported that statins might have a potential benefit for TNBCs associated with ets-1 overexpression. The aim of this study is to investigate the role of PTEN loss in the effects of statin on TNBC cells.

ERK/MAPK pathways play critical roles in EGFR ligands-induced MMP1 expression.

Activation of epidermal growth factor receptor (EGFR)-induced signaling pathways has been correlated with tumor progression, invasion and metastasis in a variety of cancers including breast carcinoma, but the underlying mechanism is not well understood. Matrix metalloproteinases (MMPs) have been implicated in cancer invasion and metastasis for their extracellular matrix (ECM)-proteolytic activity. However, the correlation of EGFR pathway with MMP expression in breast cancer has not been established.

Matrix metalloproteinase-1 expression can be upregulated through mitogen-activated protein kinase pathway under the influence of human epidermal growth factor receptor 2 synergized with estrogen receptor.

In our previous work, Ets-1 upregulates human epidermal growth factor receptor 2 (HER2) induced matrix metalloproteinase 1 (MMP-1) expression. Based on the above knowledge and result, we hypothesized that estrogen receptor (ER) and its signaling pathway may affect MMP-1 expression under the influence of HER2. In addition, we investigated how the HER2 pathway cross-talk with the ER signaling pathway in genomic and nongenomic action of ER using reverse transcription-PCR, Western blot analysis, and ELISA assay.

Ets-1 upregulates HER2-induced MMP-1 expression in breast cancer cells.

The human epidermal growth factor receptor-2 (HER2) plays an important role in breast cancer. Enhanced Ets-1 activity has recently been shown to be associated with breast cancer pathogenesis. To test the role of Ets-1 in breast cancer cells in relation to the expression of HER2 and MMP-1, we transiently overexpressed Ets-1 and/or HER2 in MCF-7 breast cancer cells and comprehensively searched for genes related to HER2 and Ets-1 using cDNA microarray analysis.