dc.contributor.author | Sipos, O | |
dc.contributor.author | Tovey, H | |
dc.contributor.author | Quist, J | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Nowinski, S | |
dc.contributor.author | Gazinska, P | |
dc.contributor.author | Kernaghan, S | |
dc.contributor.author | Toms, C | |
dc.contributor.author | Maguire, S | |
dc.contributor.author | Orr, N | |
dc.contributor.author | Linn, SC | |
dc.contributor.author | Owen, J | |
dc.contributor.author | Gillett, C | |
dc.contributor.author | Pinder, SE | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Tutt, A | |
dc.contributor.author | Cheang, MCU | |
dc.contributor.author | Grigoriadis, A | |
dc.date.accessioned | 2020-11-27T15:48:10Z | |
dc.date.issued | 2021-01-01 | |
dc.identifier.citation | Annals of oncology : official journal of the European Society for Medical Oncology, 2021, 32 (1), pp. 58 - 65 | |
dc.identifier.issn | 0923-7534 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4243 | |
dc.identifier.eissn | 1569-8041 | |
dc.identifier.doi | 10.1016/j.annonc.2020.10.475 | |
dc.description.abstract | BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays. Seven published [allelic imbalanced CNA (AiCNA); allelic balanced CNA (AbCNA); copy number neutral loss of heterozygosity (CnLOH); number of telomeric allelic imbalances (NtAI); BRCA1-like status; percentage of genome altered (PGA); homologous recombination deficiency (HRD) scores] and two novel [Shannon diversity index (SI); high-level amplifications (HLAMP)] CIN-measurements were derived. HLAMP was defined based on the presence of at least one of the top 5% amplified cytobands located on 1q, 8q and 10p. Continuous CIN-measurements were divided into tertiles. All nine CIN-measurements were used to analyse objective response rate (ORR) and progression-free survival (PFS). RESULTS: Patients with tumours without HLAMP had a numerically higher ORR and significantly longer PFS in the carboplatin (C) than in the docetaxel (D) arm [56% (C) versus 29% (D), PHLAMP,quiet = 0.085; PFS 6.1 months (C) versus 4.1 months (D), Pinteraction/HLAMP = 0.047]. In the carboplatin arm, patients with tumours showing intermediate telomeric NtAI and AiCNA had higher ORR [54% (C) versus 20% (D), PNtAI,intermediate = 0.03; 62% (C) versus 33% (D), PAiCNA,intermediate = 0.076]. Patients with high AiCNA and PGA had shorter PFS in the carboplatin arm [3.4 months (high) versus 5.7 months (low/intermediate); and 3.8 months (high) versus 5.6 months (low/intermediate), respectively; Pinteraction/AiCNA = 0.027, Padj.interaction/AiCNA = 0.125 and Pinteraction/PGA = 0.053, Padj.interaction/PGA = 0.176], whilst no difference was observed in the docetaxel arm. CONCLUSIONS: Patients with tumours lacking HLAMP and demonstrating intermediate CIN-measurements formed a subgroup benefitting from carboplatin relative to docetaxel treatment within the TNT trial. This suggests a complex and paradoxical relationship between the extent of genomic instability in primary tumours and treatment response in the metastatic setting. | |
dc.format | Print-Electronic | |
dc.format.extent | 58 - 65 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | ELSEVIER | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Chromosomal Instability | |
dc.subject | Trinitrotoluene | |
dc.subject | Carboplatin | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Phenotype | |
dc.subject | Triple Negative Breast Neoplasms | |
dc.subject | Biomarkers | |
dc.title | Assessment of structural chromosomal instability phenotypes as biomarkers of carboplatin response in triple negative breast cancer: the TNT trial. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-10-13 | |
rioxxterms.versionofrecord | 10.1016/j.annonc.2020.10.475 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2021-01 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Annals of oncology : official journal of the European Society for Medical Oncology | |
pubs.issue | 1 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials | |
pubs.publication-status | Published | |
pubs.volume | 32 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Clinical Trials & Statistics Unit | |
icr.researchteam | Genomic Analysis – Clinical Trials | |
dc.contributor.icrauthor | Tovey, Holly | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Bliss, Judith | |
dc.contributor.icrauthor | Tutt, Andrew | |
dc.contributor.icrauthor | Cheang, Chon | |