Molecular Profiling for Breast Cancer: A Comprehensive Review

Kittaneh, Muaiad; Montero, Alberto J.; Glück, Stefan

doi:10.4137/bic.s9455

Cited by 174 publications

(155 citation statements)

References 60 publications

(81 reference statements)

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“…While such approaches encompass up to thousands of analytes, it is relevant that analysis of !100 genes in PCR-based tests are informative. Examples include the recently FDA approved 70 gene MammaPrint assay test that functions as a specific and crucial aspect of metastatic and recurrent potential for breast cancer (Kittaneh et al 2013) as well as FibroSure (FibroTest) Hanley & McNeil (1982). b Binomial exact.…”

Section: Discussionmentioning

confidence: 99%

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

103

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A critical requirement in neuroendocrine tumor (NET) management is a sensitive, specific and reproducible blood biomarker test. We evaluated a PCR-based 51 transcript signature (NETest) and compared it to chromogranin A (CgA), pancreastatin (PST) and neurokinin A (NKA). The multigene signature was evaluated in two groups: i) a validation set of 40 NETs and controls and ii) a prospectively collected group of NETs (nZ41, 61% small intestinal, 50% metastatic, 44% currently treated and 41 age-sex matched controls). Samples were analyzed by a two-step PCR (51 marker genes) protocol and ELISAs for CgA, PST and NKA. Sensitivity comparisons included c 2 , non-parametric measurements, ROC curves and predictive feature importance (PFAI) analyses. NETest identified 38 of 41 NETs. Performance metrics were: sensitivity 92.8%, specificity 92.8%, positive predictive value 92.8% and negative predictive value 92.8%. Single analyte ELISA metrics were: CgA 76, 59, 65, and 71%; PST 63, 56, 59, and 61% and NKA 39, 93, 84, and 60%. The AUCs (ROC analysis) were: NETest: 0.96G0.025, CgA: 0.67G0.06, PST 0.56G0.06, NKA: 0.66G0.06. NETest significantly outperformed single analyte tests (area differences: 0.284-0.403, Z-statistic 4.85-5.9, P!0.0001). PFAI analysis determined NETest had most value (69%) in diagnosis (CgA (13%), PST (9%), and NKA (9%)). Test data were consistent with the validation set (NETest O95% sensitivity and specificity, AUC Z0.98 vs single analytes: 59-67% sensitivity, AUCs: 0.58-0.63). The NETest is significantly more sensitive and efficient (O93%) than single analyte assays (CgA, PST or NKA) in NET diagnosis. Blood-based multigene analytic measurement will facilitate early detection of disease recurrence and can predict therapeutic efficacy.

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Section: Discussionmentioning

confidence: 99%

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Modlin

Drozdov

Alaimo

et al. 2014

Endocrine-Related Cancer

103

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“…Expression profiling studies have allowed the categorization of breast carcinomas into different subtypes including luminal, HER2, and basallike (Kittaneh et al 2013;Rivenbark et al 2013). The luminal tumors harbor the expression of estrogen receptor (ER) and progesterone receptor (PR) and are responsive to antihormonal treatment.…”

Section: Introductionmentioning

confidence: 99%

Characterization of type III TGF‐β receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer

Pang

Virani

Kidwell

et al. 2014

Journal of Cell Communication and Signaling

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Invasive breast carcinomas are heterogeneous and exhibit distinct molecular features and biological behavior. Understanding the underlying molecular events that promote breast cancer progression is necessary to improve treatment and prognostication. TGF-β receptor III (TBR3) is a member of the TGF-β signaling pathway, with functions in cell proliferation and migration in malignancies, including breast cancer. Recent studies propose that TBR3 may function as a tumor suppressor and that its loss may correlate with disease progression. However, there are limited data on the expression of TBR3 in breast cancer in relationship to tumor type, hormonal receptor status and HER-2/neu, and patient outcome. In this study, we investigated the expression of TBR3 in a cohort of 205 primary invasive breast carcinomas in tissue microarrays (TMAs), with comprehensive clinical, pathological and follow-up information. Sections were stained for TBR3 and evaluated for intensity of reactivity based on a 4-tiered scoring system (1 to 4; TBR3 low=scores 1-2; TBR3 high=scores 3-4). Of the 205 invasive carcinomas, 123 were luminal type (95 type A, 28 type B), 8 were HER-2 type, and 62 were triple negative (TN). TBR3 was high in 112 (55 %) and low in 93 (45 %) cases. Low TBR3 was associated with higher histological grade and worse disease free and overall survival, all features of biologically aggressive breast carcinomas. TBR3 was significantly associated with the subtype of breast cancer, as low TBR3 was detected in 95 % of TN compared to 22 % of luminal tumors ( p<0.0001). We discovered a significant association between low TBR3 protein expression, TN breast cancer phenotype, and disease progression. These data suggest that TBR3 loss might be linked to the development of TN breast cancers and pave the way to investigating whether restoring TBR3 function may be a therapeutic strategy against TN breast carcinomas.

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“…Inhibition of apoptosis by survivin is a predictor of poor prognosis and shorter survival in patients suffering from various carcinomas [13] . In this review, we analysed the literature data regarding the correlation of survivin isoforms with clinicopathological characteristics of breast cancer and their prognostic significance in order to explore the inclusion of survivin isoforms -besides wild-type survivin-as prognostic biomarkers in emerging multiparameter technologies examining tissue RNA expression (analogous to Oncotype, Mammaprint, PAM50 [14,15] or their clinical use in target-oriented therapies.…”

Section: Topic Highlightmentioning

confidence: 99%

“…In the future, it would be very intriguing to explore the inclusion of the other survivin isoforms as prognostic biomarkers in such emerging multiparameter technologies examining tissue expression (analogous to Oncotype, Mammaprint, PAM50 etc. [14][15] since it has been proved that they possess potential importance in apoptosis and proliferation of breast cancer cells, especially when compared to wild-type full-length survivin.…”

Section: Genomic Expression Assays and Survivinmentioning

confidence: 99%

Association of survivin splice variants with prognosis and treatment of breast cancer

Pavlidou

Kroupis

Dimas

2014

WJCO

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The purpose of this study was the overview of current knowledge regarding the use of survivin and its isoforms in prognosis and treatment of breast cancer. An advanced search of Medline was performed using the following search strategy: "(survivin isoforms) OR (survivin transcript variants) AND (breast cancer) AND (neoplasm OR tumor OR cancer OR carcinoma)". Relevant studies were retrieved and processed thoroughly in order to analyze the related data. Besides wild-type survivin full-length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients, while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Survivin gene; Isoforms; Therapy; Prognosis; Breast cancer Core tip: Besides wild type survivin full length transcript, another six splice variants have been identified. Overexpression of survivin and its isoforms leads to shorter overall and disease-free survival; the transcript variants are positively correlated with apoptosis and could assist prognosis prediction. It has been proved through numerous studies that inhibiting survivin isoforms might become a promising target of drug therapy of carcinomas. Use of small molecule YM155 could offer new therapy for triple negative breast cancer patients while, chemotherapy with 5-fluorouracil + epirubicin + cyclophosphamide and Tax-Epi could be guided by survivin splice variants measurements. Survivin transcript variants could become prognostic biomarkers and could provide information about clinical management of patients suffering from breast cancer.Pavlidou A, Kroupis C, Dimas K. Association of survivin splice variants with prognosis and treatment of breast cancer. World J

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Molecular Profiling for Breast Cancer: A Comprehensive Review

Cited by 174 publications

References 60 publications

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

A multianalyte PCR blood test outperforms single analyte ELISAs (chromogranin A, pancreastatin, neurokinin A) for neuroendocrine tumor detection

Characterization of type III TGF‐β receptor expression in invasive breast carcinomas: a potential new marker and target for triple negative breast cancer

Association of survivin splice variants with prognosis and treatment of breast cancer

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