2023
Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer
Kyalwazi B, Yau C, Campbell M, Yoshimatsu T, Chien A, Wallace A, Forero-Torres A, Pusztai L, Ellis E, Albain K, Blaes A, Haley B, Boughey J, Elias A, Clark A, Isaacs C, Nanda R, Han H, Yung R, Tripathy D, Edmiston K, Viscusi R, Northfelt D, Khan Q, Asare S, Wilson A, Hirst G, Lu R, Symmans W, Yee D, DeMichele A, van ’t Veer L, Esserman L, Olopade O. Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer. JAMA Network Open 2023, 6: e2349646. PMID: 38153734, PMCID: PMC10755617, DOI: 10.1001/jamanetworkopen.2023.49646.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsDisease-Free SurvivalFemaleHumansRacial GroupsRetrospective StudiesTranscriptomeConceptsDistant recurrence-free survivalPathologic complete responseErbB2-negative tumorsWorse distant recurrence-free survivalEarly breast cancerWhite patientsBreast cancerBlack patientsGene expression signaturesReceptor subtypesStage II/III breast cancerHigh-risk early breast cancerCox proportional hazards regression modelHigh-risk breast cancerClinical trial end pointsProportional hazards regression modelsTumor receptor subtypeRetrospective cohort studyPrimary tumor sizeRecurrence-free survivalTrial end pointsBreast cancer outcomesLong-term outcomesHazards regression modelsExpression signaturesAssessment of stained direct cytology smears of breast cancer for whole transcriptome and targeted messenger RNA sequencing
Marczyk M, Fu C, Lau R, Du L, Trevarton A, Sinn B, Gould R, Pusztai L, Hatzis C, Symmans W. Assessment of stained direct cytology smears of breast cancer for whole transcriptome and targeted messenger RNA sequencing. Cancer Cytopathology 2023, 131: 289-299. PMID: 36650408, PMCID: PMC10614161, DOI: 10.1002/cncy.22679.Peer-Reviewed Original ResearchConceptsCytology smearsBreast cancerConcordance correlation coefficientTumor tissue samplesParaffin-embedded sectionsClinical diagnostic proceduresSurgical resectionRNA sequencingTumor stromaCytologic specimensDiagnostic proceduresLin's concordance correlation coefficientPapanicolaou stainCancerTissue samplesDNA mutation testingSmearsSimilar concordanceTranscriptome RNA-SeqDiagnostic cytologyAllele fractionExpression levelsRNA-seqExpression of genesGene expression levels
2021
Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples
Fu C, Marczyk M, Samuels M, Trevarton AJ, Qu J, Lau R, Du L, Pappas T, Sinn BV, Gould RE, Pusztai L, Hatzis C, Symmans WF. Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples. BMC Cancer 2021, 21: 114. PMID: 33541297, PMCID: PMC7860187, DOI: 10.1186/s12885-021-07814-8.Peer-Reviewed Original ResearchConceptsPolymerase chain reactionParaffin-embedded tumor tissue samplesConcordance correlation coefficientFresh frozenFFPE samplesPrimary breast cancerMulti-gene signatureTumor tissue samplesActivating point mutationMutant allele fractionReverse transcriptionKey breast cancer genesGene expression signaturesBreast cancer genesPIK3CA mutationsBackgroundOur objectiveBreast cancerWhole transcriptome RNAseqTumor samplesLin's concordance correlation coefficientHormone receptorsFF samplesTissue samplesExpression signaturesChain reaction
2019
Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial.
Sharma P, Barlow WE, Godwin AK, Parkes EE, Knight LA, Walker SM, Kennedy RD, Harkin DP, Logan GE, Steele CJ, Lambe SM, Badve S, Gökmen-Polar Y, Pathak HB, Isakova K, Linden HM, Porter P, Pusztai L, Thompson AM, Tripathy D, Hortobagyi GN, Hayes DF. Validation of the DNA Damage Immune Response Signature in Patients With Triple-Negative Breast Cancer From the SWOG 9313c Trial. Journal Of Clinical Oncology 2019, 37: 3484-3492. PMID: 31657982, PMCID: PMC7194448, DOI: 10.1200/jco.19.00693.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesTriple-negative breast cancerDisease-free survivalOverall survivalImmune response signaturesBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalParaffin-embedded tumor tissueThird of patientsTumor-infiltrating lymphocytesSubgroup of patientsCox regression modelResponse signatureAdjuvant ACAdjuvant doxorubicinSTIL densityT2N0 diseaseAC chemotherapyNodal statusPrognostic roleImproved prognosisPrognostic valueTumor sizePrognostic marker
2018
An integrative bioinformatics approach reveals coding and non-coding gene variants associated with gene expression profiles and outcome in breast cancer molecular subtypes
Győrffy B, Pongor L, Bottai G, Li X, Budczies J, Szabó A, Hatzis C, Pusztai L, Santarpia L. An integrative bioinformatics approach reveals coding and non-coding gene variants associated with gene expression profiles and outcome in breast cancer molecular subtypes. British Journal Of Cancer 2018, 118: 1107-1114. PMID: 29559730, PMCID: PMC5931099, DOI: 10.1038/s41416-018-0030-0.Peer-Reviewed Original ResearchConceptsHER2-negative tumorsBreast cancer patientsCancer patientsER-positive/HER2-negative tumorsBreast cancer molecular subtypesMETABRIC data setMolecular breast cancer subtypesCox regression analysisBreast cancer subtypesCancer molecular subtypesGene expression profilesMann-Whitney U testRegression analysisMultivariate regression analysisPrognostic valueKaplan-MeierBreast cancerClinical dataDisease outcomeTCGA cohortGene expressionMolecular subtypesCancer-associated genesCancer-related genesClinical relevance
2017
Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer
Safonov A, Jiang T, Bianchini G, Győrffy B, Karn T, Hatzis C, Pusztai L. Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer. Cancer Research 2017, 77: 3317-3324. PMID: 28428277, DOI: 10.1158/0008-5472.can-16-3478.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesBreast cancer subtypesImmune infiltrationNeoantigen loadImmune surveillanceLower clonal heterogeneityCancer subtypesHigher immune gene expressionClonal heterogeneityImmune checkpoint inhibitorsMajor breast cancer subtypesFavorable prognostic factorTriple-negative cancersOverall mutation loadImmune gene expressionCheckpoint inhibitorsCancer Genome AtlasPrognostic factorsImmune metagenesBreast cancerCNV loadMutation loadGermline polymorphismsCancerCancer ResIntegrated MicroRNA–mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer
Bottai G, Diao L, Baggerly KA, Paladini L, Győrffy B, Raschioni C, Pusztai L, Calin GA, Santarpia L. Integrated MicroRNA–mRNA Profiling Identifies Oncostatin M as a Marker of Mesenchymal-Like ER-Negative/HER2-Negative Breast Cancer. International Journal Of Molecular Sciences 2017, 18: 194. PMID: 28106823, PMCID: PMC5297825, DOI: 10.3390/ijms18010194.Peer-Reviewed Original ResearchConceptsEpidermal growth factorExpression profilesMessenger RNA (mRNA) expression profilesMiRNA-regulated pathwaysAvailable gene expression profilesOncostatin M signalingMesenchymal-like breast cancer cellsGene expression profilesRNA expression profilesImmune-related pathwaysPathway regulationGlobal miRNAOncogenic networksGene expressionSpecific miRNAsPathway analysisBreast cancer cellsHuman estrogen receptorTriple-negative breast cancerEMT pathwayMesenchymal transitionMiRNAMRNA dataOncostatin MCancer cells
2016
Is precision medicine ready for use in breast cancer?
Pusztai L. Is precision medicine ready for use in breast cancer? Clinical Advances In Hematology And Oncology 2016, 14: 964-966. PMID: 28212357.Peer-Reviewed Original Research
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 riskRiskHealthPatientsIncidentalomeMainstayDiseaseOncologyProfilingCharacterization of DNA variants in the human kinome in breast cancer
Agarwal D, Qi Y, Jiang T, Liu X, Shi W, Wali VB, Turk B, Ross JS, Fraser Symmans W, Pusztai L, Hatzis C. Characterization of DNA variants in the human kinome in breast cancer. Scientific Reports 2015, 5: 14736. PMID: 26420498, PMCID: PMC4588561, DOI: 10.1038/srep14736.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenetic VariationHigh-Throughput Nucleotide SequencingHumansMiddle AgedMutationNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPhosphotransferasesPolymorphism, Single NucleotideReproducibility of ResultsTranscriptomeConceptsBreast cancerHuman kinomeKinase geneGreater mutational loadNucleic acid variationPrimary cancer samplesPrimary breast cancerHistologic grade 1Major functional impactSOLiD sequencing platformIndividual breast cancersNon-synonymous variantsFine-needle biopsyGrade 3 casesCancer-related genesNucleotide variationsDNA variantsSequencing platformsMetastatic lesionsMutational loadAcid variationsCancer biologyGenesNeedle biopsyAdditional cancers
2014
Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer
Pusztai L, Moulder S, Altan M, Kwiatkowski D, Valero V, Ueno NT, Esteva FJ, Avritscher R, Qi Y, Strauss L, Hortobagyi GN, Hatzis C, Symmans WF. Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer. Clinical Cancer Research 2014, 20: 5265-5271. PMID: 25172932, DOI: 10.1158/1078-0432.ccr-14-0800.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerPredictive gene signaturesGene signatureClinical benefitBiopsy-related adverse eventsSingle-agent activityStable diseaseDasatinib therapyAdverse eventsUnderwent biopsyUnselected patientsPreclinical evidenceUnexpected toxicitiesThree-armPatientsSingle agentMolecular testingCLIA laboratoryDasatinib responseDasatinibBiopsyGene expression profilingCancerExpression profilingDynamic classification using case‐specific training cohorts outperforms static gene expression signatures in breast cancer
Győrffy B, Karn T, Sztupinszki Z, Weltz B, Müller V, Pusztai L. Dynamic classification using case‐specific training cohorts outperforms static gene expression signatures in breast cancer. International Journal Of Cancer 2014, 136: 2091-2098. PMID: 25274406, PMCID: PMC4354298, DOI: 10.1002/ijc.29247.Peer-Reviewed Original ResearchEffects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer
Fuentes-Mattei E, Velazquez-Torres G, Phan L, Zhang F, Chou PC, Shin JH, Choi HH, Chen JS, Zhao R, Chen J, Gully C, Carlock C, Qi Y, Zhang Y, Wu Y, Esteva FJ, Luo Y, McKeehan WL, Ensor J, Hortobagyi GN, Pusztai L, Symmans W, Lee MH, Yeung SC. Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer. Journal Of The National Cancer Institute 2014, 106: dju158. PMID: 24957076, PMCID: PMC4110474, DOI: 10.1093/jnci/dju158.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipokinesAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCell ProliferationDisease Models, AnimalEverolimusFemaleHumansKaplan-Meier EstimateMetforminMiceMice, TransgenicMiddle AgedObesityPostmenopauseProspective StudiesProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSirolimusTOR Serine-Threonine KinasesTranscriptomeConceptsEstrogen receptor-positive breast cancerReceptor-positive breast cancerBreast cancer cell proliferationEffect of obesityBreast cancer patientsObese mouse modelAdipocyte-secreted adipokineCancer cell proliferationCancer patientsBreast cancerMouse modelCell proliferationAssociation of obesityAkt/mTOR activationMammary tumor growthEpithelial-mesenchymal transition genesAKT/mTOR pathwayBreast cancer aggressivenessBreast tumor formationCancer hallmarksPostmenopausal womenPretreatment biopsiesProspective cohortAdipokine secretionCancer death
2013
DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes
Santarpia L, Iwamoto T, Di Leo A, Hayashi N, Bottai G, Stampfer M, André F, Turner NC, Symmans WF, Hortobágyi GN, Pusztai L, Bianchini G. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes. The Oncologist 2013, 18: 1063-1073. PMID: 24072219, PMCID: PMC3805146, DOI: 10.1634/theoncologist.2013-0163.Peer-Reviewed Original ResearchConceptsResidual invasive cancerHER2-negative tumorsInvasive cancerER-positive/HER2-negative tumorsPredictive valueUntreated breast cancer patientsAffymetrix gene expression profilesHER2-negative subgroupMolecular breast cancer subtypesTaxane/anthracyclinePathological complete responseER-positive tumorsAnthracycline-treated patientsHER2-positive tumorsBreast cancer patientsER-negative tumorsBreast cancer subtypesAnthracycline regimensComplete responseBetter prognosisClinical outcomesBC patientsPoor prognosisPredictive factorsPrognostic value
2012
Adjuvant Therapy in Stage I Carcinoma of the Breast: The Influence of Multigene Analyses and Molecular Phenotyping
Schwartz GF, Bartelink H, Burstein HJ, Cady B, Cataliotti L, Fentiman IS, Holland R, Hughes KS, Masood S, McCormick B, Palazzo JA, Pressman PI, Reis‐Filho J, Pusztai L, Rutgers EJ, Seidman AD, Solin LJ, Sparano JA. Adjuvant Therapy in Stage I Carcinoma of the Breast: The Influence of Multigene Analyses and Molecular Phenotyping. The Breast Journal 2012, 18: 303-311. PMID: 22759093, DOI: 10.1111/j.1524-4741.2012.01264.x.Peer-Reviewed Original ResearchConceptsStage I carcinomaAdjuvant therapyBreast cancerGene prognostic signaturePatient ageTumor sizeImmunohistochemical markersIndividual patientsConsensus conferencePrognostic signatureSteroid hormonesMolecular profilingNottingham indexMolecular phenotypingPatientsCarcinomaTherapyCancerBreastPrognosisPart of decisionHormone
2011
A clinically relevant gene signature in triple negative and basal-like breast cancer
Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, Gaetje R, Solbach C, Ahr A, Metzler D, Schmidt M, Müller V, Holtrich U, Kaufmann M. A clinically relevant gene signature in triple negative and basal-like breast cancer. Breast Cancer Research 2011, 13: r97. PMID: 21978456, PMCID: PMC3262210, DOI: 10.1186/bcr3035.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBasal-like triple-negative breast cancerBreast cancerPrognostic markerMolecular subtypesMultivariate analysisBasal-like molecular subtypeClaudin-low molecular subtypeBasal-like breast cancerAttractive novel therapeutic targetB cell presenceHigh expressionER-positive cancersHigh histological gradeHigher B cellsIL-8 pathwayIL-8 activityNegative breast cancerNew prognostic markerNovel therapeutic targetBiology-based therapiesNon-neoplastic cell populationsRelevant gene signaturesRoutine clinicopathological variablesResultsSeventy-three percent