2023
Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response
Bosi C, Bartha Á, Galbardi B, Notini G, Naldini M, Licata L, Viale G, Mariani M, Pistilli B, Ali H, André F, Piras M, Callari M, Barreca M, Locatelli A, Viganò L, Criscitiello C, Pusztai L, Curigliano G, Győrffy B, Dugo M, Bianchini G. Pan-cancer analysis of antibody-drug conjugate targets and putative predictors of treatment response. European Journal Of Cancer 2023, 195: 113379. PMID: 37913680, DOI: 10.1016/j.ejca.2023.113379.Peer-Reviewed Original ResearchConceptsGenotype-Tissue Expression (GTEx) databaseAntibody-drug conjugatesADC targetPan-cancer analysisCancer Genome AtlasExpression distributionGene expressionNew therapeutic opportunitiesTreatment responseExpression of determinantsPrimary tissuesGenome AtlasExpression levelsNormal tissuesPotential downstreamProtein expressionRelative expressionExpression databaseGenesTherapeutic opportunitiesExpressionTarget expressionMRNA levelsCancer typesInter-patient heterogeneityIntratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer
Kahn A, Golestani R, Harigopal M, Pusztai L. Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer. Breast Cancer Research And Treatment 2023, 201: 289-298. PMID: 37378695, DOI: 10.1007/s10549-023-06977-1.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPD-L1 expressionBreast cancerPD-L1Metastatic triple-negative breast cancerPD-L1 positive casesEarly-stage breast cancerPD-L1 protein expressionImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusProtein expressionWhole study populationPrimary breast tumorsNegative breast cancerConcordant negative resultsCheckpoint inhibitorsMultiple biopsiesPositive cancersCohen's kappa coefficientStudy populationE1L3N antibodyDiscordance rateBreast tumorsPositive cases
2022
PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer
Rozenblit M, Blenman K, Harigopal M, Reisenbichler E, Singh K, Qing T, Ibrahim E, Ramkissoon S, Asmelash S, Lin HK, Roberts M, Ross J, Huang RSP, Pusztai L. PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer. Breast Cancer Research And Treatment 2022, 196: 221-227. PMID: 36028784, DOI: 10.1007/s10549-022-06712-2.Peer-Reviewed Original ResearchConceptsPD-L1 positivityPD-L1 protein expressionPD-L1 expressionGrade 3 cancersPD-L1TIL scoreTumor gradeMultivariate analysisHigher PD-L1 positivityTumor-infiltrating lymphocyte countsConclusionPD-L1 expressionProtein expressionPD-L1 immunohistochemistryChi-square testResultsPD-L1T1 cancersLymphocyte countT3 tumorsIndependent predictorsTumor sizeLarge tumorsPositivity rateCell positivityBreast cancerGrade 2Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue
Fernandez AI, Liu M, Bellizzi A, Brock J, Fadare O, Hanley K, Harigopal M, Jorns JM, Kuba MG, Ly A, Podoll M, Rabe K, Sanders MA, Singh K, Snir OL, Soong TR, Wei S, Wen H, Wong S, Yoon E, Pusztai L, Reisenbichler E, Rimm DL. Examination of Low ERBB2 Protein Expression in Breast Cancer Tissue. JAMA Oncology 2022, 8: 1-4. PMID: 35113160, PMCID: PMC8814969, DOI: 10.1001/jamaoncol.2021.7239.Peer-Reviewed Original ResearchConceptsBreast cancer biopsiesT-DXdCancer biopsiesLarge randomized clinical trialsRandomized clinical trialsERBB2 protein expressionCentral pathology laboratoryBreast cancer tissuesAmerican Pathologists surveysStudy of concordanceTrastuzumab deruxtecanERBB2 positivityPatient populationClinical trialsScore 0Breast cancerImmunohistochemistry scoreCancer tissuesIHC assaysPatientsPathology laboratoryProtein expressionBiopsyIHCConcordance
2021
P33.02 Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients
Moutafi M, Tao W, Huang R, Haberberger J, Alexander B, Ramkissoon S, Ross J, Syrigos K, Wei W, Pusztai L, Rimm D, Vathiotis I. P33.02 Comparison of PD-L1 Protein Expression Between Primary and Metastatic Lesions in Lung Cancer Patients. Journal Of Thoracic Oncology 2021, 16: s405-s406. DOI: 10.1016/j.jtho.2021.01.671.Peer-Reviewed Original Research
2020
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expression
2019
Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial.
Wulfkuhle J, Yau C, Wolf D, Gallagher R, Brown Swigart L, Hirst G, Campbell M, Nanda R, Liu M, Pusztai L, Esserman L, Berry D, van 't Veer L, Petricoin E. Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial. Journal Of Clinical Oncology 2019, 37: 2631-2631. DOI: 10.1200/jco.2019.37.15_suppl.2631.Peer-Reviewed Original ResearchI-SPY 2 TRIALImmune checkpoint inhibitorsCheckpoint inhibitorsTumor epitheliumPD1 inhibitor pembrolizumabTumor antigen presentationHER2-negative subtypeMHC-II expressionTumor cell expressionPredictors of responseWilcoxon rank sum testPositive associationRank sum testProtein expression levelsImmune activationControl armAntigen presentationResponse predictorsHR subgroupsB cellsCell expressionPatientsSum testProtein expressionTumorsImmune 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 function
2018
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort B
2017
Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance
Pelekanou V, Carvajal-Hausdorf DE, Altan M, Wasserman B, Carvajal-Hausdorf C, Wimberly H, Brown J, Lannin D, Pusztai L, Rimm DL. Effect of neoadjuvant chemotherapy on tumor-infiltrating lymphocytes and PD-L1 expression in breast cancer and its clinical significance. Breast Cancer Research 2017, 19: 91. PMID: 28784153, PMCID: PMC5547502, DOI: 10.1186/s13058-017-0884-8.Peer-Reviewed Original ResearchConceptsStromal tumor-infiltrating lymphocytesPD-L1 expressionTumor-infiltrating lymphocytesRecurrence-free survivalNeoadjuvant chemotherapyResidual cancer tissueTIL countBreast cancerCancer tissuesDeath ligand 1 (PD-L1) protein expressionNode-positive breast cancerImproved recurrence-free survivalPD-L1 protein expressionHigher TIL countsPD-L1 statusProtein expressionBreast cancer patientsBreast cancer tissuesPost-treatment samplesPrechemotherapy samplesTIL infiltrationResidual cancerImmune markersResidual diseasePatient cohort
2015
Predictive and Prognostic Value of the TauProtein in Breast Cancer.
Bonneau C, Gurard-Levin ZA, Andre F, Pusztai L, Rouzier R. Predictive and Prognostic Value of the TauProtein in Breast Cancer. Anticancer Research 2015, 35: 5179-84. PMID: 26408675.Peer-Reviewed Original ResearchConceptsBreast cancerTau protein expressionTau proteinPrognostic valueTau expressionHuman epidermal growth factor receptor 2 (HER2) expressionEpidermal growth factor receptor 2 expressionLow tau expressionProtein expressionSubset of patientsReceptor 2 expressionIncreased response rateEffects of taxanesNodal statusBetter prognosisPredictive markerTaxane resistanceChemotherapy sensitivityPredictive valueResponse ratePubMed databaseDrug resistanceCancerHormone receptorsTaxanes
2013
Biomarker 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
2009
Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial
Pusztai L, Jeong JH, Gong Y, Ross JS, Kim C, Paik S, Rouzier R, Andre F, Hortobagyi GN, Wolmark N, Symmans WF. Evaluation of Microtubule-Associated Protein-Tau Expression As a Prognostic and Predictive Marker in the NSABP-B 28 Randomized Clinical Trial. Journal Of Clinical Oncology 2009, 27: 4287-4292. PMID: 19667268, PMCID: PMC2744271, DOI: 10.1200/jco.2008.21.6887.Peer-Reviewed Original ResearchMeSH KeywordsAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinEstrogen Receptor alphaFemaleFollow-Up StudiesHumansImmunohistochemistryKaplan-Meier EstimateMaleMicrotubule-Associated ProteinsMiddle AgedMultivariate AnalysisPaclitaxelPredictive Value of TestsPrognosisProportional Hazards ModelsRandomized Controlled Trials as TopicReceptor, ErbB-2Tau ProteinsConceptsDisease-free survivalOverall survivalTau protein expressionTau expressionEndocrine therapyPaclitaxel chemotherapyClinical trialsHuman epidermal growth factor receptor 2 (HER2) expressionEpidermal growth factor receptor 2 expressionBetter disease-free survivalWorse disease-free survivalD. Anderson Cancer CenterPrimary breast cancer specimensCourses of doxorubicinHER2-positive statusHormone receptor positiveNational Surgical BreastAdjuvant endocrine therapyPercent of patientsProtein expressionGreater tumor sizeER-positive statusEstrogen receptor-positive statusLow histologic gradeAnderson Cancer CenterEvaluation of microtubule associated protein tau expression as prognostic and predictive marker in the NSABP-B 28 randomized clinical trial.
Pusztai L, Jeong J, Gong Y, Ross J, Kim C, Hortobagyi G, Paik S, Symmans W. Evaluation of microtubule associated protein tau expression as prognostic and predictive marker in the NSABP-B 28 randomized clinical trial. Cancer Research 2009, 69: 54. DOI: 10.1158/0008-5472.sabcs-54.Peer-Reviewed Original ResearchOverall survivalTau protein expressionTau expressionClinical trialsHormone receptor-positive tumorsMD Anderson Cancer CenterDoxorubicin/cyclophosphamideER-negative subsetNational Surgical BreastAdjuvant endocrine treatmentProtein expressionReceptor-positive tumorsPercent of tumorsAnderson Cancer CenterNormal breast epitheliumAdjuvant chemotherapyPaclitaxel efficacyBowel ProjectEndocrine therapyEndocrine treatmentPaclitaxel chemotherapyNodal statusBetter prognosisClinical outcomesPositive tumors
2005
Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry
Pawlik TM, Fritsche H, Coombes KR, Xiao L, Krishnamurthy S, Hunt KK, Pusztai L, Chen JN, Clarke CH, Arun B, Hung MC, Kuerer HM. Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry. Breast Cancer Research And Treatment 2005, 89: 149-157. PMID: 15692757, DOI: 10.1007/s10549-004-1710-4.Peer-Reviewed Original ResearchConceptsBreast cancer patientsCancer patientsBreast cancerHealthy volunteersNoncancerous breastHealthy womenProtein expressionEarly-stage breast cancerUnilateral invasive breast carcinomaCancer-bearing breastsUnilateral breast cancerNAF samplesInvasive breast carcinomaBreast cancer screeningHealthy female volunteersPrimary carcinomaCancer screeningSurface-enhanced laser desorption ionization mass spectrometryBreast carcinomaTumor markersPatientsStage IFemale volunteersProtein chip arraysBreast