2024
Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial
Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothé F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nature Communications 2024, 15: 10402. PMID: 39613746, PMCID: PMC11607438, DOI: 10.1038/s41467-024-54621-3.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm Recurrence, LocalPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabTumor MicroenvironmentConceptsHER2-positive breast cancerMolecular subtypesBreast cancerRate of pathological complete responseSensitive to HER2-targeted therapiesClinical trialsRisk of distant recurrenceBreast cancer molecular subtypesPathological complete responseHER2-targeted therapyCancer molecular subtypesPotential clinical implicationsNeoALTTO trialDistant recurrenceComplete responseAdjuvant trastuzumabPrognostic/predictive valueHeterogeneous biologySurvival outcomesI-SPY2Clinical outcomesMicroenvironment featuresGene expression profilesExternal cohortTumor
2023
Assessment 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 ResearchMeSH KeywordsBreast NeoplasmsFemaleFormaldehydeGene Expression ProfilingHumansParaffin EmbeddingRNASequence Analysis, RNATissue FixationTranscriptomeConceptsCytology 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
21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer
Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, Lin NU, Perez EA, Goldstein LJ, Chia SKL, Dhesy-Thind S, Rastogi P, Alba E, Delaloge S, Martin M, Kelly CM, Ruiz-Borrego M, Gil-Gil M, Arce-Salinas CH, Brain EGC, Lee ES, Pierga JY, Bermejo B, Ramos-Vazquez M, Jung KH, Ferrero JM, Schott AF, Shak S, Sharma P, Lew DL, Miao J, Tripathy D, Pusztai L, Hortobagyi GN. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. New England Journal Of Medicine 2021, 385: 2336-2347. PMID: 34914339, PMCID: PMC9096864, DOI: 10.1056/nejmoa2108873.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleGene Expression ProfilingHumansLymphatic MetastasisMiddle AgedNeoplasm Recurrence, LocalPostmenopausePremenopauseProspective StudiesReceptor, ErbB-2Receptors, SteroidReverse Transcriptase Polymerase Chain ReactionConceptsInvasive disease-free survivalDistant relapse-free survivalDisease-free survivalRelapse-free survivalChemotherapy benefitRecurrence scoreBreast cancerChemoendocrine therapyAdjuvant chemotherapyPostmenopausal womenPremenopausal womenLymph nodesAxillary lymph node-negative breast cancerLymph node-negative breast cancerPositive axillary lymph nodesHER2-negative breast cancerNode-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Positive lymph node diseasePositive lymph nodesSecondary end pointsAxillary lymph nodesLymph node diseaseGrowth factor receptor 2Targeted 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 ResearchMeSH KeywordsBiomarkers, TumorFormaldehydeGene Expression ProfilingHumansMutationNeoplasmsParaffin EmbeddingPrognosisSequence Analysis, RNASpecimen HandlingTissue FixationTranscriptomeConceptsPolymerase 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
The impact of RNA extraction method on accurate RNA sequencing from formalin-fixed paraffin-embedded tissues
Marczyk M, Fu C, Lau R, Du L, Trevarton AJ, Sinn BV, Gould RE, Pusztai L, Hatzis C, Symmans WF. The impact of RNA extraction method on accurate RNA sequencing from formalin-fixed paraffin-embedded tissues. BMC Cancer 2019, 19: 1189. PMID: 31805884, PMCID: PMC6896723, DOI: 10.1186/s12885-019-6363-0.Peer-Reviewed Original ResearchConceptsBreast cancerFresh frozenParaffin-embedded tumor samplesFF samplesFFPE samplesConcordance correlation coefficientMixed-effects model analysisBreast cancer signaturesQiagen RNeasy kitWhole transcriptome RNA sequencingParaffin-embedded tissuesTranscriptome RNA sequencingLinear mixed-effects model analysisGene expression signaturesDifferent kitsClinical trialsGene signatureTumor samplesGene expressionTranslational researchCancerTissue samplesExpression signaturesArchival formalinSimilar concordanceIdentification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer
Wali VB, Patwardhan GA, Pelekanou V, Karn T, Cao J, Ocana A, Yan Q, Nelson B, Hatzis C, Pusztai L. Identification and Validation of a Novel Biologics Target in Triple Negative Breast Cancer. Scientific Reports 2019, 9: 14934. PMID: 31624295, PMCID: PMC6797726, DOI: 10.1038/s41598-019-51453-w.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic AgentsBreastCell Line, TumorCell MembraneCell ProliferationDatasets as TopicDrug DevelopmentFemaleGABA-A Receptor AntagonistsGene Expression ProfilingGene Knockdown TechniquesHumansImmunoconjugatesImmunoglobulin Fab FragmentsMaytansineMiceMolecular Targeted TherapyReceptors, GABA-ATriple Negative Breast NeoplasmsXenograft Model Antitumor AssaysConceptsTriple-negative breast cancerNegative breast cancerTNBC cell growthBreast cancerMDA-MB-468 xenograftsPotential novel therapeutic targetNovel biologic targetsNovel therapeutic targetBreast cancer tissuesReceptors/cellAntibody-drug conjugate (ADC) developmentMost normal tissuesTreatment optionsCell growthTherapeutic targetBiologic targetsNude miceCancer tissuesVivo functional assaysLow expressionNormal tissuesNovel targetCancerSignificant anticancer activityADC developmentImmune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
Li X, Warren S, Pelekanou V, Wali V, Cesano A, Liu M, Danaher P, Elliott N, Nahleh ZA, Hayes DF, Hortobagyi GN, Barlow WE, Hatzis C, Pusztai L. Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial. Journal For ImmunoTherapy Of Cancer 2019, 7: 88. PMID: 30967156, PMCID: PMC6457012, DOI: 10.1186/s40425-019-0563-7.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual diseaseTIL countGene expression levelsHigh expressionCellular stressNeoadjuvant chemotherapyImmune genesImmune-related genesStromal genesImmune functionImmune microenvironment changesMost immune functionsGenesCell typesPD-L1 protein expressionStem cellsHigher TIL countsPD-L1 expressionExpression levelsPrimary breast cancerT-cell markersImmune cell typesProtein expressionStromal functionImmune 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
2017
Association Between Genomic Metrics and Immune Infiltration in Triple-Negative Breast Cancer
Karn T, Jiang T, Hatzis C, Sänger N, El-Balat A, Rody A, Holtrich U, Becker S, Bianchini G, Pusztai L. Association Between Genomic Metrics and Immune Infiltration in Triple-Negative Breast Cancer. JAMA Oncology 2017, 3: 1707-1711. PMID: 28750120, PMCID: PMC5824276, DOI: 10.1001/jamaoncol.2017.2140.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCohort StudiesGene DosageGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic HeterogeneityHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingPrognosisSequence Analysis, DNASequence Analysis, RNASurvival AnalysisTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerImmune infiltrationTNBC cohortBetter prognosisPrognostic categoriesPoor prognosisInverse associationBreast cancerImmune surveillanceImmune checkpoint inhibitor therapyMore effective immunotherapy strategiesSubset of TNBCLow immune cell infiltrationClonal heterogeneityCheckpoint inhibitor therapySelection of patientsImmune cell infiltrationEffective immunotherapy strategiesIndependent validation cohortPatient survival informationLymphocyte countImmunotherapy strategiesInhibitor therapyNeoantigen loadValidation cohortImmune 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 ResearchMeSH KeywordsBreast NeoplasmsChromosome AberrationsFemaleGene Expression ProfilingGene Expression RegulationHumansLymphocytes, Tumor-InfiltratingTranscriptomeConceptsTumor-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 Res
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.BooksMeSH KeywordsGene Expression ProfilingGenetic TestingGenomicsHumansIncidental FindingsNeoplasmsPatient PreferenceRiskTranscriptomeTruth DisclosureConceptsTumor profilingField of oncologyTumor DNA sequencesOncology patientsIncidental discoveryPatient educationPatient's perspectivePatient decisionOncology communityClinical implicationsPatient healthGermline mutationsCancer medicineGenetic sequencingCancer therapyTherapyPotential riskRiskHealthPatientsIncidentalomeMainstayDiseaseOncologyProfilingChemotherapy and the recurrence score—results as expected?
Pusztai L. Chemotherapy and the recurrence score—results as expected? Nature Reviews Clinical Oncology 2015, 12: 690-692. PMID: 26552957, DOI: 10.1038/nrclinonc.2015.191.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsFemaleGene Expression ProfilingGenetic TestingHumansInsurance BenefitsMedicareNeoplasm Recurrence, LocalGenomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers
Khan SS, Karn T, Symmans WF, Rody A, Müller V, Holtrich U, Becker S, Pusztai L, Hatzis C. Genomic predictor of residual risk of recurrence after adjuvant chemotherapy and endocrine therapy in high risk estrogen receptor-positive breast cancers. Breast Cancer Research And Treatment 2015, 149: 789-797. PMID: 25651779, DOI: 10.1007/s10549-015-3277-7.Peer-Reviewed Original ResearchConceptsRecurrence-free survivalAdjuvant chemotherapyEndocrine therapyHigh riskOncotype DXBreast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerRisk categoriesEarly-stage estrogen receptorEndocrine therapy sensitivityGood prognosis patientsER-positive patientsHigh-risk patientsPoor prognosis groupPositive breast cancerLow-risk groupAdjuvant endocrineMultimodality therapyPrognosis patientsRisk patientsEndocrine sensitivityIndependent predictorsPrognosis groupT stageMultigene prognostic tests in breast cancer: past, present, future
Győrffy B, Hatzis C, Sanft T, Hofstatter E, Aktas B, Pusztai L. Multigene prognostic tests in breast cancer: past, present, future. Breast Cancer Research 2015, 17: 11. PMID: 25848861, PMCID: PMC4307898, DOI: 10.1186/s13058-015-0514-2.BooksConceptsER-negative cancersPrognostic valuePredictive markerBreast cancerPrognostic signatureExtended adjuvant endocrine therapyPrognostic testAdjuvant endocrine therapyCandidate predictive markersImmune gene signaturesPositive breast cancerGood prognostic valueSignificant prognostic valueTreatment response predictorsNew predictive markers
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 profilingGlobal gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue
Aktas B, Sun H, Yao H, Shi W, Hubbard R, Zhang Y, Jiang T, Ononye SN, Wali VB, Pusztai L, Symmans WF, Hatzis C. Global gene expression changes induced by prolonged cold ischemic stress and preservation method of breast cancer tissue. Molecular Oncology 2014, 8: 717-727. PMID: 24602449, PMCID: PMC4048748, DOI: 10.1016/j.molonc.2014.02.002.Peer-Reviewed Original ResearchConceptsGlobal gene expression changesGlobal gene expressionGene expression changesGenomic signaturesResponse genesGene expressionSensitive transcriptsExpression changesStress response genesCell cycle regulationSignificant transcriptional changesExpression levelsCycle regulationTranscriptional changesIndividual probe setsInduced transcriptsAffected transcriptsProtein processingEnrichment analysis
2013
Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers
Itoh M, Iwamoto T, Matsuoka J, Nogami T, Motoki T, Shien T, Taira N, Niikura N, Hayashi N, Ohtani S, Higaki K, Fujiwara T, Doihara H, Symmans WF, Pusztai L. Estrogen receptor (ER) mRNA expression and molecular subtype distribution in ER-negative/progesterone receptor-positive breast cancers. Breast Cancer Research And Treatment 2013, 143: 403-409. PMID: 24337596, DOI: 10.1007/s10549-013-2763-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsBridged-Ring CompoundsFemaleGene Expression ProfilingHumansKi-67 AntigenMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRNA, MessengerSurvival RateTaxoidsYoung AdultConceptsEstrogen receptor mRNA expressionPR-positive patientsTriple-negative cohortER-positive cancersTriple-negative cancersReceptor mRNA expressionProgesterone receptorBreast cancerMolecular subtypesER-negative/PR-positive tumorsProgesterone receptor-positive breast cancerReceptor-positive breast cancerRelapse-free survival rateMRNA expressionAdjuvant endocrine therapyMolecular subtype distributionPR-positive tumorsRoutine clinical assessmentSafe clinical approachLuminal-type cancersExpression of ESR1Adjuvant endocrineEndocrine therapyNeoadjuvant chemotherapyAffymetrix U133A gene chipsProliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers
Bianchini G, Pusztai L, Karn T, Iwamoto T, Rody A, Kelly C, Müller V, Schmidt M, Qi Y, Holtrich U, Becker S, Santarpia L, Fasolo A, Del Conte G, Zambetti M, Sotiriou C, Haibe-Kains B, Symmans WF, Gianni L. Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers. Breast Cancer Research 2013, 15: r86. PMID: 24060333, PMCID: PMC3978752, DOI: 10.1186/bcr3481.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalBiomarkers, TumorBreast NeoplasmsCell ProliferationChemoradiotherapy, AdjuvantEstrogensFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedMitosisNeoplasm GradingNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptors, EstrogenRiskSignal TransductionTamoxifenConceptsNode-negative tumorsLate relapseNeoadjuvant letrozoleEndocrine therapyEarly relapseNegative tumorsBreast cancerEstrogen receptor-positive breast cancerProliferation markersReceptor-positive breast cancerER-positive breast cancerAdjuvant endocrine therapyAffymetrix gene expression profilesExtended endocrine therapyTamoxifen-treated patientsER-positive patientsGenomic grade indexPositive breast cancerRisk of recurrenceRisk of relapseEstrogen receptor activitySmall independent cohortEstrogen-related genesAdjuvant tamoxifenSystemic therapyBayesian Mixture Models for Assessment of Gene Differential Behaviour and Prediction of pCR through the Integration of Copy Number and Gene Expression Data
Trentini F, Ji Y, Iwamoto T, Qi Y, Pusztai L, Müller P. Bayesian Mixture Models for Assessment of Gene Differential Behaviour and Prediction of pCR through the Integration of Copy Number and Gene Expression Data. PLOS ONE 2013, 8: e68071. PMID: 23874497, PMCID: PMC3709899, DOI: 10.1371/journal.pone.0068071.Peer-Reviewed Original ResearchBiomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer
Horak CE, Pusztai L, Xing G, Trifan OC, Saura C, Tseng LM, Chan S, Welcher R, Liu D. Biomarker Analysis of Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early-Stage Breast Cancer. Clinical Cancer Research 2013, 19: 1587-1595. PMID: 23340299, DOI: 10.1158/1078-0432.ccr-12-1359.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily B, Member 1Biomarkers, TumorBreast NeoplasmsCyclophosphamideDoxorubicinEpothilonesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMicrofilament ProteinsMicrotubule-Associated ProteinsNeoadjuvant TherapyNeoplasm ProteinsNuclear ProteinsPaclitaxelPrognosisTubulinConceptsMDR1 protein expressionNeoadjuvant doxorubicin/cyclophosphamideEarly-stage breast cancerDoxorubicin/cyclophosphamidePositive patientsProtein expressionTreatment armsBreast cancerPathologic complete response rateEfficacy of ixabepiloneInvasive breast adenocarcinomaComplete response ratePhase II trialCore needle biopsyRates of pCRΒIII-tubulin proteinNeoadjuvant settingII trialNegative patientsGene expressionPrimary cancerPredictive biomarkersPredictive markerRisk ratioNeedle biopsy