2023
Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency
Stecklein S, Barlow W, Pusztai L, Timms K, Kennedy R, Logan G, Seitz R, Badve S, Gökmen-Polar Y, Porter P, Linden H, Tripathy D, Hortobagyi G, Godwin A, Thompson A, Hayes D, Sharma P. Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency. JCO Precision Oncology 2023, 7: e2300197. PMID: 37972336, PMCID: PMC10681491, DOI: 10.1200/po.23.00197.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyBreast cancerAdjuvant anthracycline-based chemotherapyTherapeutic vulnerabilitiesRecombination deficiencyDistinct therapeutic vulnerabilitiesAnthracycline-based chemotherapyImmune response signaturesDNA-damaging therapiesFavorable prognosisIntermediate prognosisWorse prognosisImmunologic microenvironmentImmune responseChemoresistant tumorsPrognostic classificationHeterogeneous diseasePrognosisHeterogeneous groupDistinct subgroupsTumorsCancerResponse signatureSimultaneous assessmentIn silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer
Lu L, Ma W, Johnson C, Khan S, Irwin M, Pusztai L. In silico designed mRNA vaccines targeting CA-125 neoantigen in breast and ovarian cancer. Vaccine 2023, 41: 2073-2083. PMID: 36813666, PMCID: PMC10064809, DOI: 10.1016/j.vaccine.2023.02.048.Peer-Reviewed Original ResearchConceptsMRNA vaccinesOvarian cancerT cell responsesMutation-derived neoantigensT cell epitopesSARS-CoV-2Multiple neoantigensCytotoxic CD8Dendritic cellsCA 125Cancer vaccinesPatient survivalImmune responseCell epitopesNeoepitope peptidesNeoantigensVaccineCell responsesCancerBreastReverse vaccinologyCD8CD40LIFNNeoepitopes
2021
Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial
Pusztai L, Yau C, Wolf DM, Han HS, Du L, Wallace AM, String-Reasor E, Boughey JC, Chien AJ, Elias AD, Beckwith H, Nanda R, Albain KS, Clark AS, Kemmer K, Kalinsky K, Isaacs C, Thomas A, Shatsky R, Helsten TL, Forero-Torres A, Liu MC, Brown-Swigart L, Petricoin EF, Wulfkuhle JD, Asare SM, Wilson A, Singhrao R, Sit L, Hirst GL, Berry S, Sanil A, Asare AL, Matthews JB, Perlmutter J, Melisko M, Rugo HS, Schwab RB, Symmans WF, Yee D, Van't Veer LJ, Hylton NM, DeMichele AM, Berry DA, Esserman LJ. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell 2021, 39: 989-998.e5. PMID: 34143979, PMCID: PMC11064785, DOI: 10.1016/j.ccell.2021.05.009.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerI-SPY2 trialBreast cancerNeoadjuvant chemotherapyStage II/III HER2-negative breast cancerStage II/III breast cancerGrade 3 adverse eventsPathologic complete response ratePD-L1 inhibitor durvalumabMast cell signaturePaclitaxel neoadjuvant chemotherapyComplete response rateHER2-negative patientsStandard neoadjuvant chemotherapyHER2-negative cancersPARP inhibitor olaparibAdverse eventsGene expression signaturesCare controlSuperior efficacyImmune responseResponse rateCancerInhibitor olaparibDiverse 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
Association of T- and B-cell receptor repertoires with molecular subtypes and outcome in HER2+ breast cancer: An analysis of the NeoALTTO clinical trial.
Rediti M, Venet D, Rothe F, Qing T, Maetens M, Bradbury I, Izquierdo M, Di Cosimo S, Hilbers F, Bajji M, Harbeck N, Untch M, Liu M, Saura C, Huober J, Nuciforo P, Salgado R, Loi S, Pusztai L, Sotiriou C. Association of T- and B-cell receptor repertoires with molecular subtypes and outcome in HER2+ breast cancer: An analysis of the NeoALTTO clinical trial. Journal Of Clinical Oncology 2020, 38: 511-511. DOI: 10.1200/jco.2020.38.15_suppl.511.Peer-Reviewed Original ResearchPathological complete responseBreast cancerPAM50 subtypesB cell receptorImmune responseBiomarker-driven treatment strategiesTumor-infiltrating lymphocyte levelsBaseline tumor biopsiesEvent-free survivalPhase III trialsAnti-HER2 treatmentGrade 3 tumorsEstrogen receptor statusImproved clinical outcomesProportional hazards modelIII trialsLymphocyte levelsComplete responseReceptor statusClinical outcomesClinicopathological characteristicsBC subtypesClinical trialsTreatment strategiesTumor biopsies
2017
Immune gene signatures in triple-negative breast cancers characterized by varying levels of chromosomal instability.
Gyorffy B, Bottai G, Nagy A, Pusztai L, Santarpia L. Immune gene signatures in triple-negative breast cancers characterized by varying levels of chromosomal instability. Journal Of Clinical Oncology 2017, 35: 1096-1096. DOI: 10.1200/jco.2017.35.15_suppl.1096.Peer-Reviewed Original ResearchTriple-negative breast cancerCytotoxic T cellsNatural killerDendritic cellsT cellsImmune infiltrationBreast cancerTNBC samplesB cellsImmune gene signaturesOverall good prognosisKaplan-Meier analysisMann-Whitney U testChromosomal instabilityWarrants further investigationImmune infiltratesBetter prognosisTNBC patientsTNBC tumorsImmune metagenesMS tumorsImmune responseBetter survivalImmune componentsTherapeutic strategies
2016
New Strategies in Breast Cancer: Immunotherapy
Pusztai L, Karn T, Safonov A, Abu-Khalaf MM, Bianchini G. New Strategies in Breast Cancer: Immunotherapy. Clinical Cancer Research 2016, 22: 2105-2110. PMID: 26867935, PMCID: PMC9359478, DOI: 10.1158/1078-0432.ccr-15-1315.Peer-Reviewed Original ResearchConceptsBreast cancerClinical trialsEffective immune checkpoint inhibitorsObjective tumor response rateEstrogen receptor-positive cancersLocal antitumor immune responsePhase I clinical trialImmune checkpoint inhibitorsTumor response rateAntitumor immune responseReceptor-positive cancersTriple-negative cancersLocal immune microenvironmentHER2-positive cancersMost breast cancersNew treatment modalitiesCheckpoint inhibitorsDurable responsesL1 antibodyLymphocytic infiltrationImmune microenvironmentImmune infiltrationTreatment modalitiesImmune responsePreclinical studies
2015
Immunotherapy opportunities in breast cancer.
Pusztai L, Ladányi A, Székely B, Dank M. Immunotherapy opportunities in breast cancer. Magyar Onkológia 2015, 60: 34-40. PMID: 26934349.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseLocal anti-tumour immune responseBreast cancerImmune responseClinical trialsEffective immune checkpoint inhibitorsEarly-stage breast cancerTriple-negative breast cancerPhase I clinical trialImmune checkpoint inhibitorsTumor response rateExtensive lymphocytic infiltrationPD-L1 antibodiesDirect clinical evidenceBreast cancer patientsStage breast cancerNew treatment modalitiesNegative breast cancerCheckpoint inhibitorsChemotherapy regimensMetastatic settingNeoadjuvant chemotherapyLymphocytic infiltrationClinical benefitClinical evidence
2012
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer
Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, Esteva FJ, Egan SE, Zacksenhaus E. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5832-5837. PMID: 22460789, PMCID: PMC3326451, DOI: 10.1073/pnas.1201105109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCalcium-Binding ProteinsCD24 AntigenCell DifferentiationCell DivisionEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsMiceNeoadjuvant TherapyNeoplastic Stem CellsPrognosisReceptor, ErbB-2Serrate-Jagged ProteinsSignal TransductionTrastuzumabTreatment OutcomeConceptsTumor-initiating cellsMammary tumor-initiating cellsBreast cancerClinical outcomesPrognostic signatureHuman epidermal growth factor receptorAnti-HER2 drugsAnti-HER2 therapyHigh-risk patientsHigh-risk subgroupsEpidermal growth factor receptorGrowth factor receptorBC cohortRisk patientsAggressive diseaseBC patientsRetrospective analysisImmune responsePrognostic powerTumor growthPatientsChemotherapyFactor receptorCancerFraction of cells
2011
Melanoma antigen family A identified by the bimodality index defines a subset of triple negative breast cancers as candidates for immune response augmentation
Karn T, Pusztai L, Ruckhäberle E, Liedtke C, Müller V, Schmidt M, Metzler D, Wang J, Coombes KR, Gätje R, Hanker L, Solbach C, Ahr A, Holtrich U, Rody A, Kaufmann M. Melanoma antigen family A identified by the bimodality index defines a subset of triple negative breast cancers as candidates for immune response augmentation. European Journal Of Cancer 2011, 48: 12-23. PMID: 21741824, DOI: 10.1016/j.ejca.2011.06.025.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsBreast NeoplasmsCancer VaccinesCarcinomaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHealth Status IndicatorsHumansImmunotherapyMelanoma-Specific AntigensMicroarray AnalysisMiddle AgedReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsTriple-negative breast cancerCancer/testis antigensNegative breast cancerBreast cancerTestis antigensMelanoma antigen family AHuman epidermal growth factor receptor 2 (HER2) receptorsImmune response augmentationImmune-stimulatory drugsMAGE-A antigensHigh expressionLymph node statusDistinct disease subsetsLess prognostic valueHigher MAGELow MAGEWorse survivalNode statusPoor prognosisPrognostic valueDisease subsetsImmune infiltrationPredictive markerImmune metagenesImmune responseMultifactorial Approach to Predicting Resistance to Anthracyclines
Desmedt C, Di Leo A, de Azambuja E, Larsimont D, Haibe-Kains B, Selleslags J, Delaloge S, Duhem C, Kains JP, Carly B, Maerevoet M, Vindevoghel A, Rouas G, Lallemand F, Durbecq V, Cardoso F, Salgado R, Rovere R, Bontempi G, Michiels S, Buyse M, Nogaret JM, Qi Y, Symmans F, Pusztai L, D'Hondt V, Piccart-Gebhart M, Sotiriou C. Multifactorial Approach to Predicting Resistance to Anthracyclines. Journal Of Clinical Oncology 2011, 29: 1578-1586. PMID: 21422418, DOI: 10.1200/jco.2010.31.2231.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntigens, NeoplasmBiomarkers, TumorBiopsyBreast NeoplasmsChemotherapy, AdjuvantDNA Topoisomerases, Type IIDNA-Binding ProteinsDrug Resistance, NeoplasmEpirubicinEuropeFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoadjuvant TherapyOdds RatioPatient SelectionPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsProspective StudiesReceptor, ErbB-2Receptors, EstrogenReproducibility of ResultsRisk AssessmentRisk FactorsTexasTreatment FailureConceptsPathologic complete responseHuman epidermal growth factor receptor 2Neoadjuvant trialsTOP trialPredictive valueEstrogen receptor-negative tumorsEpidermal growth factor receptor 2High negative predictive valuePrimary end pointGrowth factor receptor 2Receptor-negative tumorsResponse/resistanceFactor receptor 2Negative predictive valueUseful clinical toolER-negative samplesA scoresAnthracycline monotherapyEvaluable patientsGene expression signaturesComplete responseBreast cancerImmune responseReceptor 2Patients