2023
Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221.
Chen C, Zirpoli G, Barlow W, Budd G, McKiver B, Pusztai L, Hortobagyi G, Albain K, Damaj M, Godwin A, Thompson A, Henry N, Ambrosone C, Stringer K, Hertz D. Vitamin D Insufficiency as a Risk Factor for Paclitaxel-Induced Peripheral Neuropathy in SWOG S0221. Journal Of The National Comprehensive Cancer Network 2023, 21: 1172-1180.e3. PMID: 37935109, PMCID: PMC10976748, DOI: 10.6004/jnccn.2023.7062.Peer-Reviewed Original ResearchConceptsChemotherapy-induced peripheral neuropathyVitamin D insufficiencyD insufficiencyVitamin DPaclitaxel scheduleMechanical hypersensitivityPeripheral neuropathyRisk factorsDeficient dietPaclitaxel-Induced Peripheral NeuropathyEarly-stage breast cancerPaclitaxel-containing chemotherapyVitamin D supplementationSufficient vitamin DVitamin D deficiencyBody mass indexMultiple logistic regressionSelf-reported raceD supplementationD deficiencySensitized miceProspective trialFemale patientsMass indexPredictive biomarkersPan-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 heterogeneityCisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial
Rodler E, Sharma P, Barlow W, Gralow J, Puhalla S, Anders C, Goldstein L, Tripathy D, Brown-Glaberman U, Huynh T, Szyarto C, Godwin A, Pathak H, Swisher E, Radke M, Timms K, Lew D, Miao J, Pusztai L, Hayes D, Hortobagyi G. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2023, 24: 162-174. PMID: 36623515, PMCID: PMC9924094, DOI: 10.1016/s1470-2045(22)00739-2.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMedian progression-free survivalProgression-free survivalMetastatic breast cancerMetastatic triple-negative breast cancerGermline BRCA1/2Phase 2 trialVeliparib groupPlacebo groupPlatinum-based chemotherapyBreast cancerHomologous recombination deficiencyAdverse eventsPARP inhibitorsEligible patientsMetastatic diseaseEastern Cooperative Oncology Group performance statusBRCA mutation-associated breast cancerInvestigator-assessed progression-free survivalTreatment-related adverse eventsRecurrent triple-negative breast cancerAcademic clinical sitesAddition of veliparibCommon grade 3Lines of chemotherapy
2022
A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy
Ibrahim EY, Munshani S, Domenicano I, Rodwin R, Nowak RJ, Pusztai L, Lustberg M, Ehrlich BE. A preliminary, prospective study of peripheral neuropathy and cognitive function in patients with breast cancer during taxane therapy. PLOS ONE 2022, 17: e0275648. PMID: 36206298, PMCID: PMC9543876, DOI: 10.1371/journal.pone.0275648.Peer-Reviewed Original ResearchConceptsNeurological side effectsSide effectsBreast cancerTaxane exposureProgressive neurological changesTaxane-based chemotherapyNon-interventional studyWeeks of treatmentEnd of treatmentIrreversible side effectsCourse of treatmentQuality of lifeTaxane therapyPeripheral neuropathyProspective studyPeripheral bloodBlood levelsCancer survivalNeuronal viabilityNeurological changesEffective treatmentChemotherapyCognitive impairmentPatientsPotential protein biomarkersTreatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials
Marczyk M, Mrukwa A, Yau C, Wolf D, Chen Y, Balassanian R, Nanda R, Parker B, Krings G, Sattar H, Zeck J, Albain K, Boughey J, Liu M, Elias A, Clark A, Venters S, Shad S, Basu A, Asare S, Buxton M, Asare A, Rugo H, Perlmutter J, DeMichele A, Yee D, Berry D, Veer L, Symmans W, Esserman L, Pusztai L, Consortium I. Treatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials. Annals Of Oncology 2022, 33: 814-823. PMID: 35513244, DOI: 10.1016/j.annonc.2022.04.072.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansNeoadjuvant TherapyNeoplasm, ResidualTreatment OutcomeConceptsTrial armsExperimental armSurvival differencesExact testPathologic complete response rateClinical trial armsI-SPY2 trialNeoadjuvant chemotherapy efficacyComplete response rateBreast cancer trialsCytotoxic efficacyFisher's exact testImpact of treatmentNeoadjuvant chemotherapyPCR ratePathologic responseResidual cancerControl cohortCancer trialsAssessed associationsChemotherapy efficacyEarly surrogateOlaparib armResponse rateHigher cytotoxic efficacy
2021
Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy
Rozenblit M, Mun S, Soulos P, Adelson K, Pusztai L, Mougalian S. Patterns of treatment with everolimus exemestane in hormone receptor-positive HER2-negative metastatic breast cancer in the era of targeted therapy. Breast Cancer Research 2021, 23: 14. PMID: 33514405, PMCID: PMC7844919, DOI: 10.1186/s13058-021-01394-y.Peer-Reviewed Original ResearchConceptsPrior endocrine therapyEndocrine therapyMetastatic breast cancerEffective treatment optionTreatment optionsBreast cancerMedian treatmentMedian OSEE therapyHormone receptor-positive HER2-negative metastatic breast cancerMultivariable Cox proportional hazards regression analysisHER2-negative metastatic breast cancerPrior treatmentCox proportional hazards regression analysisFirst-line therapy initiationProportional hazards regression analysisPrior treatment optionsLines of therapyProportion of patientsKaplan-Meier methodHazards regression analysisPatterns of treatmentElectronic health record-derived dataClinical trial dataOS benefit
2020
Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreement
2019
CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies
Feng WW, Wilkins O, Bang S, Ung M, Li J, An J, del Genio C, Canfield K, DiRenzo J, Wells W, Gaur A, Robey RB, Guo JY, Powles RL, Sotiriou C, Pusztai L, Febbraio M, Cheng C, Kinlaw WB, Kurokawa M. CD36-Mediated Metabolic Rewiring of Breast Cancer Cells Promotes Resistance to HER2-Targeted Therapies. Cell Reports 2019, 29: 3405-3420.e5. PMID: 31825825, PMCID: PMC6938262, DOI: 10.1016/j.celrep.2019.11.008.Peer-Reviewed Original ResearchConceptsFA uptakeHER2-positive breast cancerFA transporter CD36Anti-HER2 therapyBreast cancer patientsMetabolic rewiringHER2 inhibitor lapatinibMMTV-neu miceDeletion of CD36Breast cancer cellsAcquisition of resistancePoor prognosisCancer patientsHER2 inhibitionBreast cancerInhibitor lapatinibCDNA microarray analysisPharmacological inhibitionMammary tissueDe novo FA synthesisCD36Promotes ResistanceResistant cellsCancer cellsExpression increasesIdentification 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 development
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 BTQuest, 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 Society
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 ResearchT-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
Dzimitrowicz H, Berger M, Vargo C, Hood A, Abdelghany O, Raghavendra AS, Tripathy D, Valero V, Hatzis C, Pusztai L, Murthy R. T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab. Journal Of Clinical Oncology 2016, 34: 3511-3517. PMID: 27298406, PMCID: PMC6075965, DOI: 10.1200/jco.2016.67.3624.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsDisease ProgressionHumansMaytansineMiddle AgedNeoplasm MetastasisReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsRetreatmentRetrospective StudiesTrastuzumabConceptsMetastatic breast cancerHER2-positive metastatic breast cancerTumor response rateT-DM1Prior pertuzumabCancer HospitalBreast cancerMetastatic human epidermal growth factor receptorResponse rateStandard first-line therapyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2MD Anderson Cancer CenterHuman epidermal growth factor receptorFourth-line treatmentSmilow Cancer HospitalT-DM1 activityFirst-line therapyThird of patientsGrowth factor receptor 2Contemporary patient populationJames Cancer HospitalResults of patientsAdo-trastuzumab emtansineElectronic pharmacy recordsPembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study
Nanda R, Chow LQ, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V, Buisseret L. Pembrolizumab in Patients With Advanced Triple-Negative Breast Cancer: Phase Ib KEYNOTE-012 Study. Journal Of Clinical Oncology 2016, 34: 2460-2467. PMID: 27138582, PMCID: PMC6816000, DOI: 10.1200/jco.2015.64.8931.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsFemaleHumansL-Lactate DehydrogenaseMiddle AgedTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerAdvanced triple-negative breast cancerPD-L1Antitumor activityBreast cancerCell death protein 1 (PD-1) inhibitorsSingle-agent phase II studyAdvanced PD-L1Single-agent pembrolizumabStudy of immunotherapyTreatment-related deathsImmune checkpoint inhibitionPhase Ib studyPhase Ib trialPhase II studyAcceptable safety profilePD-L1 expressionOverall response rateProtein 1 inhibitorCommon toxicitiesIb trialKEYNOTE-012TNBC cohortII studyMedian duration
2015
Chemotherapy 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 ResearchPredictive 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 receptorsTaxanesMeasurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFSNeoadjuvant Chemotherapy for Breast Cancer Increases the Rate of Breast Conservation: Results from the National Cancer Database
Killelea BK, Yang VQ, Mougalian S, Horowitz NR, Pusztai L, Chagpar AB, Lannin DR. Neoadjuvant Chemotherapy for Breast Cancer Increases the Rate of Breast Conservation: Results from the National Cancer Database. Journal Of The American College Of Surgeons 2015, 220: 1063-1069. PMID: 25868410, DOI: 10.1016/j.jamcollsurg.2015.02.011.Peer-Reviewed Original ResearchConceptsNational Cancer DatabaseNeoadjuvant chemotherapyBreast preservationBreast conservationTumor sizeCancer DatabaseDefinitive breast surgerySmall institutional seriesBreast cancer increasesAdvanced nodal diseaseInvasive breast cancerYounger patient ageBreast tumor sizeLarger tumor sizeMultivariate logistic regressionHigh tumor gradeAmerican Cancer SocietyAdjuvant chemotherapyNodal diseasePrimary surgeryT4 tumorsInstitutional seriesPatient ageRetrospective reviewDistant metastasis
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 profiling