Show simple item record

dc.contributor.authorRothe, F
dc.contributor.authorSilva, M
dc.contributor.authorVenet, D
dc.contributor.authorCampbell, C
dc.contributor.authorBradbury, I
dc.contributor.authorRouas, G
dc.contributor.authorde Azambuja, E
dc.contributor.authorMaetens, M
dc.contributor.authorFumagalli, D
dc.contributor.authorRodrik-Outmezguine, V
dc.contributor.authorDi Cosimo, S
dc.contributor.authorRosa, D
dc.contributor.authorChia, S
dc.contributor.authorWardley, Andrew M
dc.contributor.authorUeno, T
dc.contributor.authorJanni, W
dc.contributor.authorHuober, J
dc.contributor.authorBaselga, J
dc.contributor.authorPiccart, M
dc.contributor.authorLoi, S
dc.contributor.authorSotiriou, C
dc.contributor.authorDawson, S
dc.contributor.authorIgnatiadis, M
dc.date.accessioned2019-04-29T09:48:59Z
dc.date.available2019-04-29T09:48:59Z
dc.date.issued2019en
dc.identifier.citationRothe F, Silva MJ, Venet D, Campbell C, Bradbury I, Rouas G, et al. Circulating tumor DNA in HER2 amplified breast cancer: a translational research substudy of the NeoALTTO phase 3 trial. Clin Cancer Res. 2019.en
dc.identifier.pmid30862692en
dc.identifier.doi10.1158/1078-0432.CCR-18-2521en
dc.identifier.urihttp://hdl.handle.net/10541/621781
dc.description.abstractPURPOSE: In the neoadjuvant treatment (NAT) setting, dual human epidermal growth factor receptor 2 (HER2) targeted therapy is associated with increased pathological complete response (pCR) rates compared to each therapy alone. Biomarkers allowing to predict treatment response during NAT are needed. We aim to evaluate whether circulating tumor DNA (ctDNA) is associated with response to anti-HER2 targeted therapy. EXPERIMENTAL DESIGN: Plasma DNA collected before NAT, at week2 and before surgery from patients enrolled in the NeoALTTOtrialwas assessed using digital PCR for PIK3CA and TP53 mutation detection. RESULTS: A total of 69 of 455 (15.2%) patients had a PIK3CA and/or TP53 mutation detected in the baseline tumor sample and evaluable ctDNA results from baseline samples. CtDNA was detected in 41%, 20% and 5% patients before NAT, at week 2 and before surgery respectively. CtDNA detection before NAT was significantly associated with older age and ER-negative status. CtDNA detection before NAT was associated with decreased odds of achieving pCR (OR 0.15, 95%CI 0.034-0.7, p=0.0089) but not with event-free survival (EFS). Analyses for EFS were underpowered. Interestingly, the patients with HER2 enriched subtype tumors and undetectable ctDNA at baseline had the highest pCR rates. By contrast, patients with persistent ctDNA detection at baseline and week 2 had the lowest rate of pCR. CONCLUSIONS: CtDNA detection before neoadjuvant anti-HER2 therapies is associated with decreased pCR rates. Interestingly, patients with HER2 enriched tumors and undetectable ctDNA at baseline had the highest pCR rates, therefore appearing as the best candidates for treatment de-escalation strategies.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1158/1078-0432.CCR-18-2521en
dc.titleCirculating tumor DNA in HER2 amplified breast cancer: a translational research substudy of the NeoALTTO phase 3 trialen
dc.typeArticleen
dc.contributor.departmentBreast Cancer Translational Research Laboratory, Queen's University Belfasten
dc.identifier.journalClinical Cancer Researchen
dc.description.noteen]


This item appears in the following Collection(s)

Show simple item record