Predictive value of HER-2 and Topoisomerase IIα in response to primary doxorubicin in breast cancer

Arriola, Edurne; Moreno, Abelardo; Varela, Mar; Serra, J.; Falo, Catalina; Benito, E.; Escobedo, A.

doi:10.1016/j.ejca.2006.06.013

Cited by 22 publications

(27 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The few neoadjuvant studies conducted to-date with single agent doxorubicin or docetaxel reported a very similar activity [23][24][25]. In our trial, ER negative status was a strong but unspecific predictor of sensitivy to either docetaxel and doxorubicine.…”

Section: Discussionsupporting

confidence: 53%

“…The correlation between TOP2A gene status/topo2a protein expression and response to anthracyclines has been addressed by a legion of studies [23,26,30,[35][36][37][38][39][40][41][42][43][44][45][46][47] and are currently a matter of considerable debate. Most studies were essentially retrospective, and included breast cancer patients treated with anthracycline combinations rather than single agent anthracycline and, therefore, the activity of the other drugs of the combination could obscure any existing relationship.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

“…[2][3][4] It has recently been proposed that the association of breast cancers harbouring HER2 amplification with response to anthracyclines [5][6][7] may be a direct result of the frequent coamplification of TOP2A, [8][9][10] which maps close to the HER2 gene. TOP2A is co-amplified with HER2 in approximately 40-50% of breast cancers, 11,12 and codes for topoisomerase IIa, a key protein involved in resolving topological problems such as DNA supercoiling, encountered during DNA transcription and replication. This enzyme is a known direct molecular target of anthracyclines.…”

mentioning

confidence: 99%

“…The genes within the SRAs on the amplicon 17q12 were correlated with gene expression data to identify additional putative oncogene candidates. Furthermore, given that the accuracy of CISH in defining HER2 and TOP2A amplifications remains contentious, 8,11 we tested whether CISH can reliably identify cases with TOP2A and HER2 co-amplification.…”

mentioning

confidence: 99%

Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines

Arriola

Marchiò

Tan

et al. 2008

Laboratory Investigation

Self Cite

138

150

View full text Add to dashboard Cite

HER2 and TOP2A are targets for the therapeutic agents trastuzumab and anthracyclines and are frequently amplified in breast cancers. The aims of this study were to provide a detailed molecular genetic analysis of the 17q12-q21 amplicon in breast cancers harbouring HER2/TOP2A co-amplification and to investigate additional recurrent co-amplifications in HER2/ TOP2A-co-amplified cancers. In total, 15 breast cancers with HER2 amplification, 10 of which also harboured TOP2A amplification, as defined by chromogenic in situ hybridisation, and 6 breast cancer cell lines known to be amplified for HER2 were subjected to high-resolution microarray-based comparative genomic hybridisation analysis. This revealed that the genomes of 12 cases were characterised by at least one localised region of clustered, relatively narrow peaks of amplification, with each cluster confined to a single chromosome arm (ie 'firestorm' pattern) and 3 cases displayed many narrow segments of duplication and deletion affecting the vast majority of chromosomes (ie 'sawtooth' pattern). The smallest region of amplification (SRA) on 17q12 in the whole series extended from 34.73 to 35.48 Mb, and encompassed HER2 but not TOP2A. In HER2/TOP2A-co-amplified samples, the SRA extended from 34.73 to 36.54 Mb, spanning a region of B1.8 Mb. Apart from HER2 and TOP2A, this region encompassed four additional genes whose expression levels as defined by quantitative real-time PCR are significantly higher in HER2/TOP2A-co-amplified vs HER2-amplified breast cancers: CASC3, CDC6, RARA and SMARCE1. Of the cell lines studied, SKBR3 and UACC812 showed HER2/TOP2A co-amplification. In conclusion, this is the first detailed genome-wide characterisation of HER2/TOP2A-amplified breast cancers; cell lines were identified that can be used to model these cancers in vitro. The 17q12 amplicon is complex and harbours multiple genes that may be associated with breast cancer development and progression, and potentially exploitable as therapeutic targets.

show abstract

“…By contrast, HER2 amplification and overexpression have been reported as predictive markers of the benefit of anthracycline treatment in the adjuvant setting (14). Because of its location in the identical amplicon on chromosome 17, the gene encoding topoisomerase Ⅱα (TOP2A) is frequently co-amplified with that of HER2 (24,25), which in turn leads to the overexpression of its protein product and possibly, to a greater sensitivity to anthracyclines (25)(26)(27). In 2011, Di Leo et al (14) performed a meta-analysis, in which they identified that HER2 amplification and TOP2A amplification and deletion may have certain value in the prediction of responsiveness to anthracycline-containing chemotherapy.…”

mentioning

confidence: 99%

Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIα

Nogi

Uchida

Kamio

et al. 2015

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. The present study retrospectively analyzed the utility of topoisomerase Ⅱα expression as a prognostic marker to predict the neoadjuvant chemotherapeutic response and survival among different breast cancer subtypes. The patients were subtyped and the expression of topoisomerase Ⅱα was determined using immunohistochemistry. All patients (n=147) received an anthracycline-containing regimen preoperatively, and 139 (95%) patients also received docetaxel. Of the 147 patients, 25 (17%) were triple-negative and 20 (17%) were human epidermal growth factor receptor 2 (HER2)-positive. Among these subtypes, a significantly higher a rate (P<0.0001) and higher incidence of topoisomerase Ⅱα expression (P=0.036) were observed compared with that in the hormone receptor-positive and HER2-negative breast cancer types. However, the expression of topoisomerase Ⅱα revealed no correlation with the treatment response or survival in any of the subtypes. Therefore, these results indicated that the favorable response to anthracycline-containing chemotherapy among triple-negative and HER2-positive breast cancer was independent of the expression of topoisomerase Ⅱα.

show abstract

Predictive value of HER-2 and Topoisomerase IIα in response to primary doxorubicin in breast cancer

Cited by 22 publications

References 30 publications

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer

Genomic analysis of the HER2/TOP2A amplicon in breast cancer and breast cancer cell lines

Triple-negative breast cancer exhibits a favorable response to neoadjuvant chemotherapy independent of the expression of topoisomerase IIα

Contact Info

Product

Resources

About