2023
Metastatic breast cancer (MBC) with ultra-high tumor mutational burden (UHTMB): A comprehensive genomic profiling (CGP) study.
Fanucci K, Lustberg M, Fischbach N, Pelletier M, Sivapiragasam A, Ashok Kumar P, Kallem M, Danziger N, Sokol E, Sivakumar S, Pavlick D, Ross J, Pusztai L. Metastatic breast cancer (MBC) with ultra-high tumor mutational burden (UHTMB): A comprehensive genomic profiling (CGP) study. Journal Of Clinical Oncology 2023, 41: 1036-1036. DOI: 10.1200/jco.2023.41.16_suppl.1036.Peer-Reviewed Original ResearchMetastatic breast cancerLobular histologyBreast cancerHER2 IHCGenomic alterationsComprehensive genomic profiling studyPD-L1 gene amplificationImmune checkpoint inhibitor treatmentMicrosatellite instabilityAxillary LN metastasisMetastatic site biopsySubset of ptsStage IV diseaseCheckpoint inhibitor treatmentPD-L1 expressionTumor mutational burdenMutations/MbMSI-high statusHER2 IHC resultsGenomic profiling studiesSite biopsiesSP142 assayLN metastasisMetastatic diseaseHigh TMB
2021
Network propagation-based prioritization of long tail genes in 17 cancer types
Mohsen H, Gunasekharan V, Qing T, Seay M, Surovtseva Y, Negahban S, Szallasi Z, Pusztai L, Gerstein MB. Network propagation-based prioritization of long tail genes in 17 cancer types. Genome Biology 2021, 22: 287. PMID: 34620211, PMCID: PMC8496153, DOI: 10.1186/s13059-021-02504-x.Peer-Reviewed Original ResearchConceptsCancer-relevant genesTail genesMobility genesNetwork propagation approachGenome-wide RNAiNetwork propagation methodCancer developmentPotential functional impactCancer cell survivalNew genesUnreported genesFunctional screeningCancer typesFunctional importanceCancer genesNovel potential therapeutic targetDriver genesCell survivalGenesMutational distributionsBiological interactionsPotential therapeutic targetFunctional impactGenomic alterationsInfrequent mutationsClinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases
Huang RSP, Haberberger J, McGregor K, Mata DA, Decker B, Hiemenz MC, Lechpammer M, Danziger N, Schiavone K, Creeden J, Graf RP, Strowd R, Lesser GJ, Razis ED, Bartsch R, Giannoudis A, Bhogal T, Lin NU, Pusztai L, Ross JS, Palmieri C, Ramkissoon SH. Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases. The Oncologist 2021, 26: 835-844. PMID: 34105210, PMCID: PMC8488784, DOI: 10.1002/onco.13855.Peer-Reviewed Original ResearchConceptsComprehensive genomic profilingPD-L1 immunohistochemistryBrain metastasesTumor mutational burdenPrimary breast carcinomaRelevant genomic alterationsBreast carcinomaPrimary tumorHigh prevalenceMutational burdenCerebrospinal fluidTissue acquisitionCatalytic polypeptide-like (APOBEC) mutational signatureGenomic alterationsPrimary breast carcinoma specimensHigh tumor mutational burdenGenomic profilingTriple-negative breast carcinomaTNBC brain metastasisCohort of patientsBrain metastasis samplesBreast carcinoma specimensHigher positive rateHigh microsatellite instabilityApolipoprotein B mRNA editing enzymeWhole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Li X, Kumar S, Harmanci A, Li S, Kitchen RR, Zhang Y, Wali VB, Reddy SM, Woodward WA, Reuben JM, Rozowsky J, Hatzis C, Ueno NT, Krishnamurthy S, Pusztai L, Gerstein M. Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers. Genome Medicine 2021, 13: 70. PMID: 33902690, PMCID: PMC8077918, DOI: 10.1186/s13073-021-00879-x.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsWhole-genome sequencingGermline single nucleotide variantsInternational Cancer Genome ConsortiumGenomic featuresGenomic alterationsGenome ConsortiumClonal architectureWhole Genomes (PCAWG) ConsortiumNon-coding regionsCancer-related pathwaysNon-IBC samplesCancer Genome Atlas ProgramMAST2 geneCopy number profilesPan-cancer analysisTGF-β pathwayGenomic architectureGenomic regionsSimilar genomic alterationsSimilar genomic characteristicsComplex SVsIBC samplesGenomic differencesOverall mutational load
2018
A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)
Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard J, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Annals Of Oncology 2018, 29: 1895-1902. PMID: 30137196, PMCID: PMC6158764, DOI: 10.1093/annonc/mdy263.Peer-Reviewed Original ResearchConceptsESMO ScaleMolecular targetsClinical actionabilityPrecision Medicine Working GroupGenomic alterationsPrecision medicineRoutine clinical decisionEvidence-based criteriaMedicine Working GroupLack of evidencePreclinical evidenceClinical benefitClinical evidencePatient populationClassification systemClinical managementCancer precision medicineInvestigational targetsPatient managementMolecular aberrationsTumor typesClinical decisionClinical targetsAvailable evidenceEuropean SocietyIncorporating Genomics Into the Care of Patients With Advanced Breast Cancer
Kratz J, Burkard M, O'Meara T, Pusztai L, Veitch Z, Bedard PL. Incorporating Genomics Into the Care of Patients With Advanced Breast Cancer. American Society Of Clinical Oncology Educational Book 2018, 38: 56-64. PMID: 30231387, DOI: 10.1200/edbk_200731.Peer-Reviewed Original ResearchConceptsBreast cancerGenomic alterationsTumor genomic heterogeneityAdvanced breast cancerMetastatic breast cancerRecurrent genomic alterationsCare of patientsGenetic diversityMetastatic tumor sitesImproved clinical careGenomic sequencingLaboratory-developed testsClinical trialsGenomic heterogeneityDrug treatmentPatient tumorsClinical careSame patientBlood samplesHeterogeneous diseaseClinical relevanceTumor sitePatientsClonal evolutionCell populations
2017
Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer
Chung JH, Pavlick D, Hartmaier R, Schrock AB, Young L, Forcier B, Ye P, Levin MK, Goldberg M, Burris H, Gay LM, Hoffman AD, Stephens PJ, Frampton GM, Lipson DM, Nguyen DM, Ganesan S, Park BH, Vahdat LT, Leyland-Jones B, Mughal TI, Pusztai L, O’Shaughnessy J, Miller VA, Ross JS, Ali SM. Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. Annals Of Oncology 2017, 28: 2866-2873. PMID: 28945887, PMCID: PMC5834148, DOI: 10.1093/annonc/mdx490.Peer-Reviewed Original ResearchConceptsEstrogen receptor-positive metastatic breast cancerMetastatic breast cancerBreast cancerGenomic profilingGenomic alterationsEstrogen receptor-positive breast cancerMetastatic breast cancer managementReceptor-positive breast cancerTumor DNACo-occurring genomic alterationsMetastatic tissue biopsiesTissue samplesRoutine clinical careBreast cancer managementCourse of diseasePeripheral blood samplesMetastatic tumor tissueMetastatic diseaseFemale patientsInvasive alternativeCtDNA fractionCancer managementClinical careBlood samplesPatientsGenomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with metastatic breast cancer (mBC).
Pusztai L, Chung J, Young L, Schrock A, Hartmaier R, Frampton G, Gay L, Stephens P, Miller V, Ali S, Ross J, Vahdat L, O'Shaughnessy J. Genomic profiling of circulating tumor DNA (ctDNA) from patients (pts) with metastatic breast cancer (mBC). Journal Of Clinical Oncology 2017, 35: 1016-1016. DOI: 10.1200/jco.2017.35.15_suppl.1016.Peer-Reviewed Original ResearchAromatase inhibitor therapyMetastatic breast cancerGenomic profilingCommon genomic alterationsGenomic alterationsTreatment informationTreatment of MBCCo-occurring genomic alterationsConcurrent genomic alterationsPrior chemotherapyInhibitor therapyD538GBreast cancerKinase fusionsTherapeutic approachesClinical careClinical decision
2014
A Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice
Vasan N, Yelensky R, Wang K, Moulder S, Dzimitrowicz H, Avritscher R, Wang B, Wu Y, Cronin MT, Palmer G, Symmans WF, Miller VA, Stephens P, Pusztai L. A Targeted Next‐Generation Sequencing Assay Detects a High Frequency of Therapeutically Targetable Alterations in Primary and Metastatic Breast Cancers: Implications for Clinical Practice. The Oncologist 2014, 19: 453-458. PMID: 24710307, PMCID: PMC4012963, DOI: 10.1634/theoncologist.2013-0377.Peer-Reviewed Original ResearchConceptsBreast cancerGenomic alterationsV-akt murine thymoma viral oncogene homolog 1Stage IV cancerMetastatic breast cancerActionable genomic alterationsPotential treatment optionOncogene homolog 1Primary tumor biopsiesCancer-related genesClinical Laboratory Improvement AmendmentsDependent kinasesMedian sequencing depthGene fusionsSequencing depthBase substitutionsHER2 mutationsHomolog 1Actionable alterationsTargetable alterationsTreatment optionsClinical trialsHER2 amplificationMetastatic cancerTumor biopsies
2013
Genomic alterations in matching primary tumors and metastasis in breast cancer.
Jiang T, Szekely B, Szasz A, Kluger Y, Kulka J, Pusztai L. Genomic alterations in matching primary tumors and metastasis in breast cancer. Journal Of Clinical Oncology 2013, 31: 1549-1549. DOI: 10.1200/jco.2013.31.15_suppl.1549.Peer-Reviewed Original ResearchPrimary tumorPrimary cancerBreast cancerMetastatic lesionsDisease historyExtensive prior therapyPrimary breast cancerLonger disease historyWhole-exome sequencingDifferent tumor sitesFunctional impactPrior therapyNucleotide variantsMetastasisPatientsTumor siteTumorsCancerNormal tissuesCancer samplesExome sequencingGenomic alterationsLesionsMore mutationsExon KitCancer heterogeneity: implications for targeted therapeutics
Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. British Journal Of Cancer 2013, 108: 479-485. PMID: 23299535, PMCID: PMC3593543, DOI: 10.1038/bjc.2012.581.Peer-Reviewed Original ResearchConceptsIntra-tumoural heterogeneityIntra-tumor heterogeneityClinical trial designCancer therapeuticsDistinct genomic alterationsClinical outcomesMalignant tumorsCurrent evidenceTrial designSolid tumorsSubpopulation of cellsSame tumorTumorsTissue collectionGenomic alterationsTherapeuticsBiomarker discoveryWidespread implementationEvidence
2012
Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC).
Pusztai L, Yelensky R, Wang B, Avritscher R, Symmans W, Lipson D, Palmer G, Moulder S, Stephens P, Wu Y, Cronin M. Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 10559-10559. DOI: 10.1200/jco.2012.30.15_suppl.10559.Peer-Reviewed Original ResearchMetastatic breast cancerClinical trialsNext-generation sequencingNeedle biopsyBreast cancerGenomic alterationsClinical treatment optionsHER2 gene amplificationPatient selection approachAdjuvant therapyTargetable alterationsTreatment optionsPIK3CA mutationsNovel agentsERBB2 alterationsInvestigational drugsTherapeutic implicationsCancer-related genesBiopsyPredictive valueProspective testingNGS profilingDriver mutationsTherapyCancer