Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay

Praly, Laurent; Fan, Cheng; Quackenbush, John; Mullins, Michael E.; Gauthier, Nicholas Paul; Nelson, Edward William; Mone, Mary C.; Hansen, Heidi; Buys, Saundra S.; Rasmussen, Karen; Orrico, Alejandra Ruiz; Dreher, Donna; Walters, Robin G.; Parker, Joel S.; Hu, Zhiyuan; He, Xiaping; Palazzo, Juan; Olopade, Olufunmilayo I.; Szabó, Anikó; Perou, Charles M.; Bernard, Philip S.

doi:10.1186/bcr1399

Cited by 181 publications

(139 citation statements)

References 33 publications

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“…On the contrary, the other group, defined by the opposite pattern of the two markers (high HER2 and low CK8 levels), presented very low or no expression levels of the ER. These data agree with the recently reported molecular classification of breast cancer [20]. Patients with negative or weakly positive ER status and higher expression levels of HER2 presented a worse outcome, in accordance with Perreard et al [20] who found ER-negative tumours more aggressive.…”

Section: Discussionsupporting

confidence: 82%

Molecular characterisation of breast cancer patients at high and low recurrence risk

Bonin

Brunetti²,

Benedetti

et al. 2008

Virchows Arch

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The ability to predict the recurrence risk in breast cancer patients is not available for the individual. It is commonly accepted that the different clinical course of tumours with identical histology and stage are the result of differences at the molecular level. This case study of 80 patients affected by breast cancer looked at the messenger ribonucleic acid expression level of 22 genes, by using quantitative reverse transcriptase-polymerase chain reaction. Our results showed that a panel of seven genes is associated to patients' survival. Moreover, the combination of two couples of genes is able to define short-and longliving cohorts of patients. In particular, our findings strongly demonstrate that retinoblastoma (RB) and cyclindependent kinase 2 (CDK2) on one side and cytokeratin 8 (CK8) and epidermal growth factor receptor 2 (HER2) on the other may affect the clinical course of the disease in 56% of patients. Groups characterised by low RB and high CDK2 as with low CK8 and high HER2 have a higher risk of recurrences and death in 5 years. The identification of these sub-groups of patients with higher risk of early relapse could have further involvement in the selection of the cases to submit to therapy against HER2 or CDK2 as a possible therapy target.

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Section: Discussionsupporting

confidence: 82%

Molecular characterisation of breast cancer patients at high and low recurrence risk

Bonin

Brunetti²,

Benedetti

et al. 2008

Virchows Arch

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“…Analysis of gene expression patterns has classified various tumors into distinct clinically and biologically significant subgroups (26)(27)(28)(29). Breast cancer has also been proved to be heterogeneous and is classified into several distinct groups based on the results of gene microarray analysis (10,13,27,(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Breast carcinomas expressing basal markers have poor clinical outcome regardless of estrogen receptor status

Shin

Lee²,

Lee³

et al. 2008

Oncol Rep

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Abstract.To evaluate the clinical significance of gene expression-based classification and define the characteristic features of the new basal-like subtype, invasive breast carcinomas were divided into ER, HER2, basal-like and null subtypes by immunohistochemical analysis. A total of 401 invasive breast carcinomas were submitted to tissue microarray and stained with ER, HER2, EGFR, c-KIT and cytokeratin (CK) 5/6. The basal-like tumors, defined as positive for one or more basal markers but negative for both ER and HER2, comprised 18.5%. They were larger (p=0.041), showed higher grade (p<0.001), and more frequently expressed p53 (p=0.003). Expression of the basal marker itself showed negative prognostic effect, particularly in node-positive group. Even ER-positive patients had far shorter disease-free survival (DFS) when the tumor coexpressed one or more basal marker (p<0.001). Discrimination of basal-like subtype or tumors positive for basal markers may be clinically significant also in the treatment and prognosis of breast carcinomas.

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“…Interestingly, MNAT1 retained significant prognostic value (p ϭ .0006) in the multivariate model, suggesting potential value in assessing prognosis over conventional proliferation markers; however, the value of MNAT1 expression requires independent confirmation. Expression levels of TOP2A and BUB1 closely reflect the proliferative activity of cells [18,29] and have been previously associated with recurrence in ER-positive/HER2-negative BC [30,31]. PCNA and POLQ are involved in genomic replication and DNA repair [32,33], and their overexpression has been correlated with poor clinical outcome in BC patients [34,35].…”

Section: Dna Repair Genes As Prognostic Factors In Breast Cancer Subtmentioning

confidence: 99%

DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

et al. 2013

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DNA repair pathways can enable tumor cells to survive DNA damage induced by chemotherapy and thus provide prognostic and/or predictive value. We evaluated Affymetrix gene expression profiles for 145 DNA repair genes in untreated breast cancer (BC) patients (n ϭ 684) and BC patients treated with regimens containing neoadjuvant taxane/anthracycline (n ϭ 294) or anthracycline (n ϭ 210). We independently assessed estrogen receptor (ER)-positive/HER2-negative, HER2-positive, and ER-negative/ HER2-negative subgroups for differential expression, bimodal distribution, and the prognostic and predictive value of DNA repair gene expression. Twenty-two genes were consistently overexpressed in ER-negative tumors, and five genes were overexpressed in ER-positive tumors, but no differences in expression were associated with HER2 status. In ER-positive/HER2-negative tumors, the expression of nine genes (BUB1, FANCI, MNAT1, PARP2, PCNA, POLQ, RPA3, TOP2A, and UBE2V2) was associated with poor prognosis, and the expression of one gene (ATM) was associated with good prognosis. Furthermore, the prognostic value of specific genes did not correlate with proliferation. A few genes were associated with chemotherapy response in BC subtypes and treatment-specific manner. In ER-negative/HER2-negative tumors, the MSH2, MSH6, and FAN1 (previously MTMR15) genes were associated with pathological complete response and residual invasive cancer in taxane/anthracycline-treated patients. Conversely, PMS2 expression was associated with residual invasive cancer in treatments using anthracycline as a single agent. In HER2-positive tumors, TOP2A was associated with patient response to anthracyclines but not to taxane/anthracycline regimens. In genes expressed in a bimodal fashion, RECQL4 was significantly associated with clinical outcome. In vitro studies showed that defects in RECQL4 impair homologous recombination, sensitizing BC cells to DNA-damaging agents. The Oncologist 2013;18:1063-1073 Implications for Practice: The identification of molecular mechanisms and biomarkers of sensitivity to chemotherapy in breast cancer is still controversial. In this context, the cellular DNA repair machinery is expected to play an important role in response to different types of chemotherapy. The differential expression of many DNA repair genes between ER-positive and ER-negative breast tumors could contribute to the different clinical behavior of these two breast cancer subtypes. We demonstrated that specific DNA repair genes are prognostic and predictive of chemotherapy response in a molecular subtype and treatment specific manner suggesting their contribution in the risk of tumor recurrence and response to chemotherapy. Such prognostic and predictive value warrant further exploration in clinical trials for optimizing treatment tailoring to improve patient outcome. Furthermore, defects of RECQL4 impair homologous recombination and sensitize breast cancer cells to DNA damaging agents, e.g., PARP inhibitors and platinum agents, which allows for selecting ...

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Classification and risk stratification of invasive breast carcinomas using a real-time quantitative RT-PCR assay

Cited by 181 publications

References 33 publications

Molecular characterisation of breast cancer patients at high and low recurrence risk

Molecular characterisation of breast cancer patients at high and low recurrence risk

Breast carcinomas expressing basal markers have poor clinical outcome regardless of estrogen receptor status

DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes

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