2022
Cancer Relevance of Human Genes
Qing T, Mohsen H, Cannataro VL, Marczyk M, Rozenblit M, Foldi J, Murray M, Townsend J, Kluger Y, Gerstein M, Pusztai L. Cancer Relevance of Human Genes. Journal Of The National Cancer Institute 2022, 114: 988-995. PMID: 35417011, PMCID: PMC9275765, DOI: 10.1093/jnci/djac068.Peer-Reviewed Original ResearchConceptsCore cancer genesHuman genesFunctional importanceSomatic mutation frequencySelection pressureGene/protein networksCancer genesHigher somatic mutation frequencyNegative selection pressureGene-gene interaction networksMutation frequencyProtein-truncating variantsGenomic contextCell viabilityGenes decreasesCancer Genome AtlasInteraction networksProtein networkCancer relevanceCancer cell viabilityCell survivalGenesCancer biologyGenome AtlasSearch tools
2021
Clinicopathologic 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 enzymeDiverse immune response of DNA damage repair-deficient tumors
Qing T, Jun T, Lindblad KE, Lujambio A, Marczyk M, Pusztai L, Huang KL. Diverse immune response of DNA damage repair-deficient tumors. Cell Reports Medicine 2021, 2: 100276. PMID: 34095878, PMCID: PMC8149377, DOI: 10.1016/j.xcrm.2021.100276.Peer-Reviewed Original ResearchConceptsCancer typesDDR-deficient tumorsImmune checkpoint inhibitorsHigh neoantigen loadDifferent immune phenotypesDiverse immune responsesAdaptive immune markersRepair-deficient tumorsDDR deficiencyCheckpoint inhibitorsImmunotherapy outcomesDNA damage repair deficiencyImmune infiltratesImmune markersNeoantigen loadSurvival outcomesImmune phenotypeTumor neoantigensImmune responseAnimal modelsGenomic biomarkersGermline mutationsPathway mutationsTumorsRepair deficiency
2020
Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer
Huang RSP, Li X, Haberberger J, Sokol E, Severson E, Duncan DL, Hemmerich A, Edgerly C, Williams E, Elvin J, Vergilio J, Killian J, Lin D, Hiemenz M, Xiao J, McEwan D, Holmes O, Danziger N, Erlich R, Frampton G, Cohen M, McGregor K, Reddy P, Cardeiro D, Anhorn R, Venstrom J, Alexander B, Brown C, Pusztai L, Ross J, Ramkissoon S. Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer. The Oncologist 2020, 25: 943-953. PMID: 32869930, PMCID: PMC7648336, DOI: 10.1634/theoncologist.2020-0449.Peer-Reviewed Original ResearchConceptsComprehensive genomic profilingPD-L1 immunohistochemistryPotential therapeutic optionBreast cancerPD-L1Therapeutic optionsTriple negative breast cancer cohortDrug AdministrationHormone receptor-positive breast cancerReceptor-positive breast cancerGenomic profilingTriple-negative breast cancerPD-L1 positivityRoutine clinical careMutations/MbBreast cancer cohortBiomarker landscapeTNBC cohortNab-paclitaxelGermline testingConsecutive patientsReceptor negativeHER2-positiveClinical trialsPIK3CA mutationsAnalysis of Pre- and Posttreatment Tissues from the SWOG S0800 Trial Reveals an Effect of Neoadjuvant Chemotherapy on the Breast Cancer Genome
Powles RL, Wali VB, Li X, Barlow WE, Nahleh Z, Thompson AM, Godwin AK, Hatzis C, Pusztai L. Analysis of Pre- and Posttreatment Tissues from the SWOG S0800 Trial Reveals an Effect of Neoadjuvant Chemotherapy on the Breast Cancer Genome. Clinical Cancer Research 2020, 26: 1977-1984. PMID: 31919134, PMCID: PMC7717064, DOI: 10.1158/1078-0432.ccr-19-2405.Peer-Reviewed Original Research
2019
Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women
O’Meara T, Safonov A, Casadevall D, Qing T, Silber A, Killelea B, Hatzis C, Pusztai L. Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women. Breast Cancer Research And Treatment 2019, 175: 247-259. PMID: 30725384, PMCID: PMC6666415, DOI: 10.1007/s10549-019-05156-5.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCaucasian breast cancersER-positive cancersBreast cancerTIL countImmune microenvironmentCaucasian patientsMolecular subtypesAA TNBCHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Pathologic complete responseGrowth factor receptor 2Immune cell distributionImmune cell populationsCancer Genome Atlas (TCGA) databaseConsistent racial differencesFactor receptor 2Immune gene expressionImmune attenuationNeoadjuvant chemotherapyLymphocyte countLymphocyte infiltrationComplete responseTNBC cases
2018
TQuest, A Web-Based Platform to Enable Precision Medicine by Linking a Tumor’s Genetic Defects to Therapeutic Options
Gershkovich P, Platt J, Knopf J, Tasoulis MK, Shi W, Pusztai L, Hatzis C. TQuest, A Web-Based Platform to Enable Precision Medicine by Linking a Tumor’s Genetic Defects to Therapeutic Options. JCO Clinical Cancer Informatics 2018, 2: 1-13. PMID: 30652574, DOI: 10.1200/cci.17.00120.Peer-Reviewed Original ResearchConceptsData acquisition layerFull-text indexAcquisition layerUser interfaceData layersPrototype web applicationWeb-based platformWeb applicationRelevance scoresSearch enginesSource codeSoftware toolsSearch resultsInterventional clinical trialsLabel dataClinical trialsTherapeutic optionsPlatformUS FoodMolecular abnormalitiesMetastatic breast cancerPotential therapeutic optionPotential treatment optionTumor DNA sequencingWeb-based modulesA 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 samplesPatients
2016
Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis
Jiang T, Shi W, Wali VB, Pongor L, Li C, Lau R, Győrffy B, Lifton RP, Symmans WF, Pusztai L, Hatzis C. Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic Analysis. PLOS Medicine 2016, 13: e1002193. PMID: 27959926, PMCID: PMC5154510, DOI: 10.1371/journal.pmed.1002193.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathologic complete responseMD Anderson Cancer CenterNegative breast cancerBreast cancerMutation burdenExtensive residual diseaseBetter survival outcomesBRCA deficiencyImmune cell activityAnderson Cancer CenterPredictor of chemosensitivityHigh mutation burdenWhole-exome sequencingACT chemotherapyMDACC cohortTNBC cohortNeoadjuvant chemotherapyCare chemotherapyTaxane chemotherapyCancer Genome AtlasComplete responseSuch patientsImproved survivalAggressive diseaseDeciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer
Santarpia L, Bottai G, Kelly CM, Győrffy B, Székely B, Pusztai L. Deciphering and Targeting Oncogenic Mutations and Pathways in Breast Cancer. The Oncologist 2016, 21: 1063-1078. PMID: 27384237, PMCID: PMC5016060, DOI: 10.1634/theoncologist.2015-0369.Peer-Reviewed Original ResearchConceptsBreast cancerCancer-causing genesCopy number variationsRNA speciesRNA editingGenomic variationNext-generation sequencingRNA sequencingGenomic complexityGenomic portraitGreater genomic complexityOncogenic mutationsOncogenic eventsTarget profilingRare mutationsMutationsRecurrent mutationsSomatic variantsGenetic aberrationsFormal clinical trialsPotential therapeutic implicationsDriver mutationsSequencingGermline variantsMolecular abnormalities
2015
Tumor profiling and the incidentalome: patient decisions and risks
Hofstatter E, Mehra K, Yushak M, Pusztai L. Tumor profiling and the incidentalome: patient decisions and risks. Future Oncology 2015, 11: 3299-3305. PMID: 26562094, DOI: 10.2217/fon.15.260.BooksConceptsTumor profilingField of oncologyTumor DNA sequencesOncology patientsIncidental discoveryPatient educationPatient's perspectivePatient decisionOncology communityClinical implicationsPatient healthGermline mutationsCancer medicineGenetic sequencingCancer therapyTherapyPotential riskRiskHealthPatientsIncidentalomeMainstayDiseaseOncologyProfiling
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 biopsiesCombined analysis of gene expression, DNA copy number, and mutation profiling data to display biological process anomalies in individual breast cancers
Shi W, Balazs B, Györffy B, Jiang T, Symmans WF, Hatzis C, Pusztai L. Combined analysis of gene expression, DNA copy number, and mutation profiling data to display biological process anomalies in individual breast cancers. Breast Cancer Research And Treatment 2014, 144: 561-568. PMID: 24619174, DOI: 10.1007/s10549-014-2904-z.Peer-Reviewed Original ResearchConceptsDNA copy numberBiological processesIndividual molecular eventsCopy numberGene expressionMolecular eventsMulticellular organismal processGene Ontology databaseGO biological processesSignal transduction pathwaysOrganismal processesGO termsMolecular dataTransduction pathwaysSiRNA screenComplex genomic abnormalitiesIndividual cancersOntology databaseFunctional roleDriver eventsCell growthSequence abnormalitiesBreast cancer cell linesCancer cell linesGenomic abnormalities
2013
Influence of genomics on adjuvant treatments for pre-invasive and invasive breast cancer
Abu-Khalaf M, Pusztai L. Influence of genomics on adjuvant treatments for pre-invasive and invasive breast cancer. The Breast 2013, 22: s83-s87. PMID: 24074799, DOI: 10.1016/j.breast.2013.07.015.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAntineoplastic Agents, HormonalBiopsy, NeedleBreast NeoplasmsChemotherapy, AdjuvantCost SavingsCost-Benefit AnalysisFemaleForecastingGenetic TestingGenomicsHumansImmunohistochemistryMiddle AgedNeoplasm InvasivenessNeoplasm StagingPrognosisReceptors, EstrogenRisk AssessmentSurvival AnalysisTreatment OutcomeConceptsLow-risk patientsBreast cancerRisk patientsTreatment recommendationsEarly-stage breast cancerER-positive breast cancerUse of chemotherapyInvasive breast cancerGenomic testingStage breast cancerInternational practice guidelinesMultivariate prognostic modelCost-effectiveness studiesPotential clinical valueAdjuvant treatmentBreast cancer biomarkersCurrent guidelinesPractice guidelinesClinical utilityClinical valueTumor markersStage IPrognostic modelPrognostic testClinical useCancer 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
Intratumor Heterogeneity: Seeing the Wood for the Trees
Yap TA, Gerlinger M, Futreal PA, Pusztai L, Swanton C. Intratumor Heterogeneity: Seeing the Wood for the Trees. Science Translational Medicine 2012, 4: 127ps10. PMID: 22461637, DOI: 10.1126/scitranslmed.3003854.Peer-Reviewed Original Research
2011
The Value of Genomic Analysis of Breast Cancer in Drug Development
Szekely B, Pusztai L. The Value of Genomic Analysis of Breast Cancer in Drug Development. JNCI Monographs 2011, 2011: 60-62. PMID: 22043042, DOI: 10.1093/jncimonographs/lgr039.Peer-Reviewed Original ResearchA Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer
Hatzis C, Pusztai L, Valero V, Booser DJ, Esserman L, Lluch A, Vidaurre T, Holmes F, Souchon E, Wang H, Martin M, Cotrina J, Gomez H, Hubbard R, Chacón JI, Ferrer-Lozano J, Dyer R, Buxton M, Gong Y, Wu Y, Ibrahim N, Andreopoulou E, Ueno NT, Hunt K, Yang W, Nazario A, DeMichele A, O’Shaughnessy J, Hortobagyi GN, Symmans WF. A Genomic Predictor of Response and Survival Following Taxane-Anthracycline Chemotherapy for Invasive Breast Cancer. JAMA 2011, 305: 1873-1881. PMID: 21558518, PMCID: PMC5638042, DOI: 10.1001/jama.2011.593.Peer-Reviewed Original ResearchMeSH KeywordsAdultAlgorithmsAnthracyclinesAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBiopsy, NeedleBreast NeoplasmsBridged-Ring CompoundsDisease-Free SurvivalDrug Resistance, NeoplasmFemaleForecastingGene Expression ProfilingGenes, erbB-2Genes, NeoplasmGenomicsHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalOligonucleotide Array Sequence AnalysisPredictive Value of TestsPrognosisProspective StudiesReceptors, EstrogenRiskTaxoidsConceptsDistant relapse-free survivalInvasive breast cancerBreast cancerGenomic predictorsD. Anderson Cancer CenterAnthracycline-based regimensER-negative subsetExcellent pathologic responseProspective multicenter studyRelapse-free survivalAbsolute risk reductionStandard cancer treatmentPredictors of responseIndependent validation cohortAnderson Cancer CenterNegative breast cancerCancer treatment strategiesSequential taxaneNeoadjuvant chemotherapyPreoperative chemotherapyPathologic responseWorse survivalEndocrine sensitivityER statusMulticenter study