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dc.contributor.authorCani, A. K.
dc.contributor.authorDolce, E. M.
dc.contributor.authorDarga, E. P.
dc.contributor.authorHu, K.
dc.contributor.authorBrown, M.
dc.contributor.authorLiu, C. J.
dc.contributor.authorPierce, Jackie
dc.contributor.authorBradbury, Kieran
dc.contributor.authorAung, K.
dc.contributor.authorSchiavon, G.
dc.contributor.authorCarroll, D.
dc.contributor.authorCarr, T. H.
dc.contributor.authorKlinowska, T.
dc.contributor.authorLindemann, J.
dc.contributor.authorMarshall, G.
dc.contributor.authorRowlands, V.
dc.contributor.authorHarrington, E. A.
dc.contributor.authorBarrett, J.
dc.contributor.authorArmstrong, Anne C
dc.contributor.authorBaird, R.
dc.contributor.authorHamilton, E.
dc.contributor.authorIm, S. A.
dc.contributor.authorJhaveri, K.
dc.contributor.authorPatel, M. R.
dc.contributor.authorDive, Caroline
dc.contributor.authorTomlins, S. A.
dc.contributor.authorUdager, A. M.
dc.contributor.authorHayes, D. F.
dc.contributor.authorPaoletti, C.
dc.date.accessioned2021-09-30T11:55:59Z
dc.date.available2021-09-30T11:55:59Z
dc.date.issued2021en
dc.identifier.citationCani AK, Dolce EM, Darga EP, Hu K, Brown M, Liu C-J, et al. Abstract 3143: Monitoring circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) genomic alterations in ER positive (POS)/HER2 negative (NEG) advanced breast cancer during endocrine therapy: correlative study of AZD9496 oral SERD phase I trial. In: Tumor Biology. American Association for Cancer Research; 2021.en
dc.identifier.doi10.1158/1538-7445.AM2021-3143en
dc.identifier.urihttp://hdl.handle.net/10541/624581
dc.description.abstractPurpose: The vast majority of advanced ER POS breast cancers eventually cease responding to endocrine (ET) and other therapies leading to evolution of lethal disease. However, timely monitoring of the molecular events associated with response/progression in tissue biopsies is logistically difficult. The use of liquid biopsies, such as CTC and ctDNA, in this context has been of recent interest. Patients and Methods: Individual CTC and ctDNA were obtained at different time points from patients with advanced ER POS/HER2 NEG breast cancer enrolled in a Phase I trial of AZD9496, an oral selective estrogen receptor degrader (SERD) ET. The CTC, purified using tandem CellSearch®/DepArray™ technologies, were genomically profiled by DNA single cell next generation sequencing (scNGS). Plasma ctDNA was isolated from blood collected in Streck BCT tubes. Genomic profiling was performed by targeted gene panel scNGS for CTC and ddPCR for ERα gene (ESR1) mutations in ctDNA. Results: 123 high-quality CTCs from 12 patients profiled by scNGS showed 100% concordance with ctDNA in detection of driver ESR1 somatic mutations. CTC scNGS additionally revealed extensive intra-patient heterogeneity of driver alterations, that would have been unresolvable by bulk ctDNA profiling, including separate subclonal CTC populations emerging within the same patient. ScNGS revealed potential opportunities for targeted therapies in 73% of patients, directed at alterations in PIK3CA, FGFR2, KIT and BRAF, at times present as 2 or more targets in the same or different cell populations. In one patient, an emergent, distinct, BRAF p.V600E targetable alteration was detected in a subpopulation of CTCs collected at the progression time point but not at baseline. Conclusion: Serial monitoring of CTC and ctDNA genomic alterations is feasible and should enable real-time tracking of response/progression, tumor evolution and opportunities for precision medicine interventions.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/ 10.1158/1538-7445.AM2021-3143en
dc.titleMonitoring circulating tumor cell (CTC) and circulating tumor DNA (ctDNA) genomic alterations in ER positive (POS)/HER2 negative (NEG) advanced breast cancer during endocrine therapy: correlative study of AZD9496 oral SERD phase I trialen
dc.typeOtheren
dc.contributor.departmentUniversity of Michigan, Ann Arbor, MIen
dc.identifier.journalCancer Researchen
dc.description.noteen]


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