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Breast Cancer Biomarkers: Utility in Clinical Practice.

ABSTRACT: Breast cancer is a heterogeneous disease. For the past decades, new technical tools have been developed for biomarkers at the DNA, RNA and protein levels to better understand the biology of breast cancer. This progress is essential to classify the disease into clinically relevant subtypes, which may lead to new therapeutic opportunities. Novel biomarker development is paramount to deliver personalized cancer therapies. Further, tumor evolution, being natural or under treatment pressure, should be monitored and "liquid biopsies" by detecting circulating tumor cells or circulating free tumor DNA in blood samples will become an important option. This paper reviews the new generation of biomarkers and the current evidence to demonstrate their analytical validity, clinical validity and clinical utility.

SUBMITTER: Le Du F

PROVIDER: S-EPMC3882751 | biostudies-other | 2013 Dec

REPOSITORIES: biostudies-other

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Breast Cancer Biomarkers: Utility in Clinical Practice.

Le Du Fanny F Ueno Naoto T NT Gonzalez-Angulo Ana M AM

Current breast cancer reports 20131201 4

Breast cancer is a heterogeneous disease. For the past decades, new technical tools have been developed for biomarkers at the DNA, RNA and protein levels to better understand the biology of breast cancer. This progress is essential to classify the disease into clinically relevant subtypes, which may lead to new therapeutic opportunities. Novel biomarker development is paramount to deliver personalized cancer therapies. Further, tumor evolution, being natural or under treatment pressure, should b ...[more]

PMID: 24416469

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Project description:Purpose: There is a quest for novel non-invasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA signatures using a cohort of Asian Chinese breast cancer patients, and to compare microRNA profiles between tumour and serum samples. Experimental design: MicroRNAs from paired breast cancer tumours, normal tissue and serum samples derived from 32 patients were comprehensively profiled using microarrays (1300 microRNAs against tumour and normal tissues) or LNA RT-PCR panels (742 microRNAs against serum samples). Serum samples from healthy individuals (n=22) were also employed as normal controls. Significant serum microRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n=82) and healthy controls (n=53). Results: The 20 most significant microRNAs differentially expressed in breast cancer tumours included miR-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Interestingly, 16 of the 20 most significant microRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these microRNAs exhibited areas under the curves of 0.944-0.946. Only seven microRNAs were overexpressed in both tumours and serum, suggesting that microRNAs may be released into the serum selectively. Conclusion: The clinical employment of microRNA signatures as a non-invasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. Blood samples were collected in Becton Dickinson (Franklin Lakes, NJ) Vacutainer SST tubes. Serum was harvested by centrifugation at 2200g after allowing blood to clot for 30mins. 32 patient samples and 22 samples from healthy controls were obtained for profiling. Sera samples were stored at -80oC.

Project description:Purpose: There is a quest for novel non-invasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA signatures using a cohort of Asian Chinese breast cancer patients, and to compare microRNA profiles between tumour and serum samples. Experimental design: MicroRNAs from paired breast cancer tumours, normal tissue and serum samples derived from 32 patients were comprehensively profiled using microarrays (1300 microRNAs against tumour and normal tissues) or LNA RT-PCR panels (742 microRNAs against serum samples). Serum samples from healthy individuals (n=22) were also employed as normal controls. Significant serum microRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n=82) and healthy controls (n=53). Results: The 20 most significant microRNAs differentially expressed in breast cancer tumours included miR-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Interestingly, 16 of the 20 most significant microRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these microRNAs exhibited areas under the curves of 0.944-0.946. Only seven microRNAs were overexpressed in both tumours and serum, suggesting that microRNAs may be released into the serum selectively. Conclusion: The clinical employment of microRNA signatures as a non-invasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. "_A" and "_B" are two tissue sections of the same sample; "_1" and "_2" represents 2 runs of the same sample; na = not available All tissue samples were histologically confirmed by a pathologist using hematoxylin and eosin staining of cryosectioned specimens. One tumour sample was rejected due to failure to detect any tumour cells. Except for two samples (with 30% and 40% tumour cells), all tumour tissues employed had a minimum of 60% tumour cells, as estimated microscopically. Overall, the breast cancer tumour samples had an average of 71% tumour cells. The criteria for adjacent normal tissue were absence of tumour cells and presence of epithelial cells. Hence, after histological confirmation, 31 breast cancer tumours and 23 matched normal tissues were employed for microRNA extraction and profiling using microarray.

Dataset Information

Breast Cancer Biomarkers: Utility in Clinical Practice.

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Breast Cancer Biomarkers: Utility in Clinical Practice.

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