Clinical utility of RT-PCR in assessing HER 2 gene expression versus traditional IHC and FISH in breast cancer patients

Multigene expression assays are prognostic for recurrence in hormone-receptor positive 2 (HER-2) negative breast cancer, and, in some cases, predictive of benefit from chemotherapy or extended endocrine therapy. The results of these assays may be used to guide treatment recommendations for early HER-2 negative breast cancer. We review the results of trials establishing the clinical utility of several commercially available gene expression assays.

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Gene expression profiling of breast cancer patients treated with docetaxel, doxorubicin, and cyclophosphamide within the GEPARTRIO trial: HER-2, but not topoisomerase II alpha and microtubule-associated protein tau, is highly predictive of tumor response

The Breast ◽

10.1016/j.breast.2006.06.008 ◽

2007 ◽

Vol 16 (1) ◽

pp. 86-93 ◽

Cited By ~ 47

Author(s):

A. Rody ◽

T. Karn ◽

R. Gätje ◽

A. Ahr ◽

C. Solbach ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Expression Profiling ◽

Topoisomerase Ii ◽

Tumor Response ◽

Breast Cancer Patients ◽

Topoisomerase Ii Alpha ◽

Protein Tau ◽

Her 2

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Expression and Prognostic Characteristics of m6 A RNA Methylation Regulators in Breast Cancer

Frontiers in Genetics ◽

10.3389/fgene.2020.604597 ◽

2020 ◽

Vol 11 ◽

Author(s):

Bo Zhang ◽

Yanlin Gu ◽

Guoqin Jiang

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

High Expression ◽

Cancer Gene ◽

Breast Cancer Patients ◽

Rna Methylation ◽

Kaplan Meier ◽

Her 2 ◽

Kaplan Meier Plotter

PurposeN6-methyladenosine (m6A) is the most prevalent modification in mRNA methylation which has a wide effect on biological functions. This study aims to figure out the efficacy of m6A RNA methylation regulator-based biomarkers with prognostic significance in breast cancer.Patients and MethodsThe 23 RNA methylation regulators were firstly analyzed through ONCOMINE, then relative RNA-seq transcriptome and clinical data of 1,096 breast cancer samples and 112 normal tissue samples were acquired from The Cancer Gene Atlas (TCGA) database. The expressive distinction was also showed by the Gene Expression Omnibus (GEO) database. The gene expression data of m6A RNA regulators in human tissues were acquired from the Genotype-Tissue Expression (GTEx) database. The R v3.5.1 and other online tools such as STRING, bc-GeneExminer v4.5, Kaplan-Meier Plotter were applied for bioinformatics analysis.ResultsResults from ONCOMINE, TCGA, and GEO databases showed distinctive expression and clinical correlations of m6A RNA methylation regulators in breast cancer patients. The high expression of YTHDF3, ZC3H13, LRPPRC, and METTL16 indicated poor survival rate in patients with breast cancer, while high expression of RBM15B pointed to a better survival rate. Both univariate and multivariate Cox regression analyses revealed that age and risk scores were related to overall survival (OS). Univariate analysis also delineated that stage, tumor (T) status, lymph node (N) status, and metastasis (M) status were associated with OS. From another perspective, Kaplan-Meier Plotter platform showed that the relatively high expression of YTHDF3 and LRPPRC and the relatively low expression of RBM15B, ZC3H13, and METTL16 in breast cancer patients had worse Relapse-Free Survival (RFS). Breast Cancer Gene-Expression Miner v4.5 showed that LRPPRC level was negatively associated with ER and PR expression, while METTL16, RBM15B, ZC3H13 level was positively linked with ER and PR expression. In HER-2 (+) breast cancer patients, the expression of LRPPRC, METTL16, RBM15B, and ZC3H13 were all lower than the HER-2 (−) group.ConclusionThe significant difference in expression levels and prognostic value of m6A RNA methylation regulators were analyzed and validated in this study. This signature revealed the potential therapeutic value of m6A RNA methylation regulators in breast cancer.

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Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20033 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20033-20033

Author(s):

N. Fersis ◽

V. Deckwart ◽

A. Leitz ◽

M. Weber ◽

J. Rom ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Breast Carcinoma ◽

Tumor Cell ◽

Cancer Patients ◽

Tumor Cells ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Her 2

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.

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Expression of Heterochromatin Protein 1 in the Primary Tumor of Breast Cancer Patients in the Presence or Absence of Occult Metastatic Cells in the Bone Marrow

The International Journal of Biological Markers ◽

10.1177/172460080802300404 ◽

2008 ◽

Vol 23 (4) ◽

pp. 219-224 ◽

Cited By ~ 1

Author(s):

A.P.S. Abreu ◽

C. Milani ◽

M.L.H. Katayama ◽

E.M. Barbosa ◽

L. Gomes da Fonseca ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Bone Marrow ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Heterochromatin Protein 1 ◽

Heterochromatin Protein ◽

Heterochromatin Formation ◽

Metastatic Cells

Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family (HP1Hsα, HP1Hsβ and HP1Hsγ), which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1Hsα, HP1Hsβ and HP1Hsγ was determined by real-time RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow.

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