Molecular Stratification of Triple-Negative Breast Cancers

Perou, Charles M.

doi:10.1634/theoncologist.2010-s5-39

Cited by 283 publications

(279 citation statements)

References 26 publications

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“…Triple-negative breast cancers (TNBCs, lacking expression of ER, PR and HER2) are a group with only chemotherapy options (Perou, 2011). Hence, these biological markers (ER, PR, and HER2) can be applied to prediction of clinical response to medical treatment and prognosis.…”

Section: 8057 Ultrasound Utility For Predicting the Biological Behavmentioning

confidence: 99%

Ultrasound Utility for Predicting Biological Behavior of Invasive Ductal Breast Cancers

Zhang

Liu²,

Jiang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Asian Pac J Cancer Prev, 15 (19), 8057-8062 IntroductionDetermination of the molecular status of invasive breast cancer is useful as a prognostic and predictive factor, and it has become standard practice in the management of breast cancer because estrogen receptor (ER) and human epidermal growth factor receptor2 (HER2) positivity predict response to endocrine therapy or targeted therapy with monoclonal antibodies directed against HER2 (Bauer et al., 2007;Doreen et al., 2011). If it is possible to predict molecular status on the basis of imaging characteristics, it could assist in both pretreatment planning and prognosis, as well as add to our understanding of the biologic behavior of this disease.Breast ultrasound has gained widespread acceptance as an adjunct to mammography in diagnosis of evaluating clinical or radiological suspected abnormalities (Gordon et al., 1995;Rizzatto et al., 2001). Stavros et al. reported that it has high sensitivity (98.4%) and negative predictive (99.5%) value for diagnosing breast cancers (Stavros et al., 1995). Ultrasound (US), with its merits of safety and low cost, is becoming a preferred method for both physicians and patients. Hence, more attention is needed toward US imaging to determine whether certain type of tumor biologic factors can be predicted from imaging appearances.A few studies have looked into correlation between

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Section: 8057 Ultrasound Utility For Predicting the Biological Behavmentioning

confidence: 99%

Ultrasound Utility for Predicting Biological Behavior of Invasive Ductal Breast Cancers

Zhang

Liu²,

Jiang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…[12][13][14][15] Furthermore, TNBCs are themselves a heterogeneous group within which the claudinlow subtype is associated with worst prognosis. 16 Compared to the overall prevalence of breast cancer, a limited number of reports have indicated exosomes and/or microvesicles to be of relevance in breast cancer. [17][18][19] The focus, however, has typically been on HER2-overexpressing cells and their exosomes.…”

Section: Introductionmentioning

confidence: 99%

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

O’Brien

Rani

Corcoran

et al. 2013

European Journal of Cancer

203

161

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Background: Triple-negative breast cancer (TNBC) accounts for 15-20% of breast cancers but is responsible for a disproportionate number of deaths. We investigated the relevance, in TNBC, of nano-sized exosomes expelled from cells. Specifically, we compared effects of exosomes derived from the claudin-low TNBC cell line Hs578T and its more invasive Hs578Ts(i) 8 variant, as well as exosomes from TNBC patient sera compared to normal sera. Methods: Exosomes were isolated from conditioned media (CM) of Hs578T and Hs578Ts(i) 8 cells and from sera by filtration and ultracentrifugation. Successful isolation was confirmed by transmission electron microscopy and immunoblotting. Subsequent analysis, of secondary/ recipient cells in response to exosomes, included proliferation; motility/migration; invasion; anoikis assays and endothelial tubule formation assays. Results: Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes significantly increased the proliferation, migration and invasion capacity of all three recipient cell lines evaluated i.e. SKBR3, MDA-MB-231 and HCC1954. Exosomes from Hs578Ts(i) 8 cells also conferred increased invasiveness to parent Hs578T cells. Hs578Ts(i) 8 -exosomes increased sensitivity of SKBR3, MDA-MB-231 and HCC1954 to anoikis when compared to the effects of Hs578T-exosomes reflecting the fact that Hs578Ts(i) 8 cells are themselves innately more sensitive to anoikis. In relation to vasculogenesis and subsequent angiogenesis, Hs578Ts(i) 8 -exosomes versus Hs578T-exosomes stimulated significantly more endothelial tubules formation. Finally, our 0959-8049/$ -see front matter Ó

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“…TNBC is clinically defined by the absence of oestrogen receptor (ER) and progesterone receptor expression, and neither overexpression nor amplification of human epidermal growth factor receptor 2 (HER2) 1,2 . TNBC represents B15-20% of all newly diagnosed breast cancer cases and is generally associated with high risk of disease recurrence and shorter overall survival compared with non-TNBC 3 .…”

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confidence: 99%

Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

et al. 2015

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Epigenetic alterations in the cancer methylome are common in breast cancer and provide novel options for tumour stratification. Here, we perform whole-genome methylation capture sequencing on small amounts of DNA isolated from formalin-fixed, paraffin-embedded tissue from triple-negative breast cancer (TNBC) and matched normal samples. We identify differentially methylated regions (DMRs) enriched with promoters associated with transcription factor binding sites and DNA hypersensitive sites. Importantly, we stratify TNBCs into three distinct methylation clusters associated with better or worse prognosis and identify 17 DMRs that show a strong association with overall survival, including DMRs located in the Wilms tumour 1 (WT1) gene, bi-directional-promoter and antisense WT1-AS. Our data reveal that coordinated hypermethylation can occur in oestrogen receptor-negative disease, and that characterizing the epigenetic framework provides a potential signature to stratify TNBCs. Together, our findings demonstrate the feasibility of profiling the cancer methylome with limited archival tissue to identify regulatory regions associated with cancer.

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Molecular Stratification of Triple-Negative Breast Cancers

Cited by 283 publications

References 26 publications

Ultrasound Utility for Predicting Biological Behavior of Invasive Ductal Breast Cancers

Ultrasound Utility for Predicting Biological Behavior of Invasive Ductal Breast Cancers

Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells

Methylome sequencing in triple-negative breast cancer reveals distinct methylation clusters with prognostic value

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