Topoisomerase IIα Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in <i>HER-2/neu</i>–Amplified Breast Cancer: Scandinavian Breast Group Trial 9401

Tanner, Minna; Isola, Jorma; Wıklund, Tom; Erikstein, Bjørn; Kellokumpu‐Lehtinen, Pirkko; Malmström, Per; Wilking, Nils; Nilsson, Jonas; Bergh, Jonas

doi:10.1200/jco.2005.02.9264

Cited by 224 publications

(137 citation statements)

References 23 publications

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“…Another recent report also showed that such post-treatment changes do exist but, as in our study, seem to be rare (Pierga et al, 2007). Whether specific molecular abnormalities can facilitate or impede response to therapy is a crucial issue in oncology (Tanner et al, 2006). However, exquisite chemosensitivity linked with specific allelic losses in tumours has not been reported yet.…”

Section: Discussionsupporting

confidence: 76%

Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

et al. 2007

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In advanced breast cancers, TP53 mutation is highly predictive of complete response to high-dose epirubicin/cyclophosphamide chemotherapy. In these tumours with an altered control of genomic stability, accumulation of chemotherapy-induced genetic alterations may contribute to cell death and account for complete response. To explore the effects of chemotherapy on stability of the tumour genome, allelic profiles were obtained from microdissected tumour samples before and after chemotherapy in 29 unresponsive breast cancers (9 with TP53 mutation). Ninety-four per cent allelic profiles remained unchanged after treatment. Interestingly, 11 profiles (6%) showed important changes after treatment; allelic imbalances significantly increased (four cases) or decreased (seven cases) after chemotherapy in three distinct experiments, two of which using laser microdissected tumour cells. These genetic changes were not linked to the TP53 status, but one tumour showed complete disappearance of TP53-mutated cells in the residual tumour after treatment. Altogether, these observations carry important implications for the clonal evolution of breast cancers treated with DNA-damaging agents, as they point both to the importance of tumour heterogeneity and chemotherapydriven selection of subclones.

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Section: Discussionsupporting

confidence: 76%

Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

et al. 2007

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“…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%

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

Martín

Romero

Cheang

et al. 2011

Breast Cancer Res Treat

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“…137 Topo-II is a major target for anthracycline compounds, and several studies have reported TOPO-II amplification to be a better predictor of anthracycline sensitivity compared with HER-2 Mapping genetic alterations causing chemoresistance PE Lønning and S Knappskog amplifications. [138][139][140] Although experimental evidence do not suggest HER-2 overexpression to cause drug resistance, 141 interestingly, one study 142 found HER-2 overexpression to be associated with improved response when adding a taxane to anthracycline-containing chemotherapy in breast cancer patients. Finally, HER-2 activates the PI3K/akt/mTOR pathway, discussed in detail below.…”

Section: Her-2 Amplification and Chemoresistancementioning

confidence: 99%

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

Lønning

Knappskog

2013

Oncogene

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Although new agents are implemented to cancer therapy, we lack fundamental understandings of the mechanisms of chemoresistance, the main obstacle to cure in cancer. Here we review clinical evidence linking molecular defects to drug resistance across different tumour forms and discuss contemporary experimental evidence exploring these mechanisms. Although evidence, in general, is sparse and fragmentary, merging knowledge links drug resistance, and also sensitivity, to defects in functional pathways having a key role in cell growth arrest or death and DNA repair. As these pathways may act in concert, there is a need to explore multiple mechanisms in parallel. Taking advantage of massive parallel sequencing and other novel high-throughput technologies and base research on biological hypotheses, we now have the possibility to characterize functional defects related to these key pathways and to design a new generation of studies identifying the mechanisms controlling resistance to different treatment regimens in different tumour forms.

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Topoisomerase IIα Gene Amplification Predicts Favorable Treatment Response to Tailored and Dose-Escalated Anthracycline-Based Adjuvant Chemotherapy in HER-2/neu–Amplified Breast Cancer: Scandinavian Breast Group Trial 9401

Abstract: Coamplification of HER-2/neu and TOP2A may define a subgroup of high-risk breast cancer patients who benefit from individually tailored and dose-escalated adjuvant anthracyclines.

Cited by 224 publications

References 23 publications

Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

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

Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers

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