2022
Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors
Kasi PM, Fehringer G, Taniguchi H, Starling N, Nakamura Y, Kotani D, Powles T, Li BT, Pusztai L, Aushev VN, Kalashnikova E, Sharma S, Malhotra M, Demko ZP, Aleshin A, Rodriguez A, Billings PR, Grothey A, Taieb J, Cunningham D, Yoshino T, Kopetz S. Impact of Circulating Tumor DNA–Based Detection of Molecular Residual Disease on the Conduct and Design of Clinical Trials for Solid Tumors. JCO Precision Oncology 2022, 6: e2100181. PMID: 35263168, PMCID: PMC8926064, DOI: 10.1200/po.21.00181.Peer-Reviewed Original ResearchMeSH KeywordsCirculating Tumor DNAClinical Trials as TopicDisease ProgressionHumansNeoplasm Recurrence, LocalNeoplasm, ResidualConceptsMolecular residual diseaseSurrogate end pointsCtDNA testingMRD detectionResidual diseaseClinical trialsCancer recurrenceTumor DNAEnd pointMRD-positive patientsUse of ctDNAHigh-risk categoryCtDNA dynamicsTrial enrichmentAccelerated approvalDifferent cancer typesCancer managementClinical utilityHigh riskClinical practiceSmall cohortSolid tumorsRecurrenceTrial durationTreatment assignment
2019
Defining Risk of Late Recurrence in Early-Stage Estrogen Receptor–Positive Breast Cancer: Clinical Versus Molecular Tools
Foldi J, O'Meara T, Marczyk M, Sanft T, Silber A, Pusztai L. Defining Risk of Late Recurrence in Early-Stage Estrogen Receptor–Positive Breast Cancer: Clinical Versus Molecular Tools. Journal Of Clinical Oncology 2019, 37: jco.18.01933. PMID: 30943126, DOI: 10.1200/jco.18.01933.Peer-Reviewed Original Research
2018
Immunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markers
2017
Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations
Brown D, Smeets D, Székely B, Larsimont D, Szász AM, Adnet PY, Rothé F, Rouas G, Nagy ZI, Faragó Z, Tőkés AM, Dank M, Szentmártoni G, Udvarhelyi N, Zoppoli G, Pusztai L, Piccart M, Kulka J, Lambrechts D, Sotiriou C, Desmedt C. Phylogenetic analysis of metastatic progression in breast cancer using somatic mutations and copy number aberrations. Nature Communications 2017, 8: 14944. PMID: 28429735, PMCID: PMC5474888, DOI: 10.1038/ncomms14944.Peer-Reviewed Original ResearchConceptsDistant metastasisPrimary tumorClonal frequency analysisMultiple metastatic lesionsBreast cancer disseminationBreast cancer progressionSomatic mutationsWhole-exome sequencingAvailable metastasesMetastatic lesionsMetastatic precursorsPrimary lesionMetastatic tumorsDisease progressionBreast cancerPatterns of disseminationMetastasisMetastatic progressionCancer disseminationPatientsCancer progressionCopy number profilingCopy number aberrationsTumorsMonoclonal origin
2016
T-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 records
2015
A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer
Generali D, Venturini S, Rognoni C, Ciani O, Pusztai L, Loi S, Jerusalem G, Bottini A, Tarricone R. A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer. Breast Cancer Research And Treatment 2015, 152: 95-117. PMID: 26044370, DOI: 10.1007/s10549-015-3453-9.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerHazard ratioMegestrol acetateResponse rateBreast cancerEstrogen receptor-positive metastatic breast cancerPFS/TTPSecond-line therapySecond-line treatmentToxicity of chemotherapyOverall response rateBetter response rateCapecitabineStandard pairwiseTamoxifenSunitinibChemotherapyTTP differenceMultiple treatmentsNMAIndividual studiesEverolimusExemestaneCancer
2013
TIG1 Promotes the Development and Progression of Inflammatory Breast Cancer through Activation of Axl Kinase
Wang X, Saso H, Iwamoto T, Xia W, Gong Y, Pusztai L, Woodward WA, Reuben JM, Warner SL, Bearss DJ, Hortobagyi GN, Hung MC, Ueno NT. TIG1 Promotes the Development and Progression of Inflammatory Breast Cancer through Activation of Axl Kinase. Cancer Research 2013, 73: 6516-6525. PMID: 24014597, PMCID: PMC6135947, DOI: 10.1158/0008-5472.can-13-0967.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisAxl Receptor Tyrosine KinaseBlotting, WesternCell AdhesionCell CycleCell MovementCell ProliferationDisease ProgressionFemaleFluorescent Antibody TechniqueHumansImmunoprecipitationInflammatory Breast NeoplasmsMediator ComplexMiceNeoplasm InvasivenessProto-Oncogene ProteinsReal-Time Polymerase Chain ReactionReceptor Protein-Tyrosine KinasesReverse Transcriptase Polymerase Chain ReactionRNA, MessengerRNA, Small InterferingSignal TransductionTumor Cells, CulturedConceptsInflammatory breast cancerBreast cancerAxl expressionMalignant propertiesHigh tumoral expressionIBC cell proliferationMatrix metalloproteinase-9Inhibited tumor growthIBC specimensIBC cellsShorter survivalTumoral expressionProteasome-dependent degradationMetalloproteinase-9TIG1 expressionNF-κBTherapeutic targetTumor growthReceptor tyrosine kinasesAxl functionLethal formAxlIBC treatmentCancerAggressive properties
2010
Stability of estrogen receptor status in breast carcinoma
Gong Y, Han EY, Guo M, Pusztai L, Sneige N. Stability of estrogen receptor status in breast carcinoma. Cancer 2010, 117: 705-713. PMID: 20939012, DOI: 10.1002/cncr.25506.Peer-Reviewed Original ResearchConceptsER statusBreast carcinomaEndocrine therapyMetastatic sitesPrimary tumorMetastatic tumorsMetastatic breast carcinomaEstrogen receptor statusER discordanceDisease courseReceptor statusSystemic therapyClinical courseER expressionER testingClinical managementNegative conversionER assaysDiscordant casesCarcinomaPositive conversionTumorsPatientsMetastasisTherapyThe role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches
Lacerda L, Pusztai L, Woodward WA. The role of tumor initiating cells in drug resistance of breast cancer: Implications for future therapeutic approaches. Drug Resistance Updates 2010, 13: 99-108. PMID: 20739212, DOI: 10.1016/j.drup.2010.08.001.Peer-Reviewed Original ResearchConceptsTumor initiating cellsInitiating cellsCancer cellsLong-term outcomesBreast cancer recurrenceFuture therapeutic approachesTumor-stromal interactionsBreast cancer cellsHedgehog inhibitor cyclopamineNeoadjuvant chemotherapyResidual diseaseEffective therapyCancer recurrenceBreast cancerTherapeutic approachesInhibitor lapatinibInhibitor cyclopamineTherapy resistanceRegulation of tumorChemical library screenDrug resistanceChemotherapy-resistant subpopulationMultidrug resistanceNovel targetResistant subpopulationsPredictors of Tumor Progression During Neoadjuvant Chemotherapy in Breast Cancer
Caudle AS, Gonzalez-Angulo AM, Hunt KK, Liu P, Pusztai L, Symmans WF, Kuerer HM, Mittendorf EA, Hortobagyi GN, Meric-Bernstam F. Predictors of Tumor Progression During Neoadjuvant Chemotherapy in Breast Cancer. Journal Of Clinical Oncology 2010, 28: 1821-1828. PMID: 20231683, PMCID: PMC2860366, DOI: 10.1200/jco.2009.25.3286.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsCarcinoma, Ductal, BreastCarcinoma, LobularChemotherapy, AdjuvantDisease ProgressionFemaleHumansMiddle AgedNeoadjuvant TherapyReceptors, EstrogenReceptors, ProgesteroneSurvival RateTaxoidsTreatment OutcomeYoung AdultConceptsHigh Ki-67 scoreNeoadjuvant chemotherapyKi-67 scoreStable diseaseBreast cancerEstrogen receptorMultivariate analysisDistant disease-free survivalER/PR negativityFirst-line surgical approachTumor progressionMost breast cancer patientsDisease-free survivalStandard neoadjuvant chemotherapyCancer clinical stageAmerican Joint CommitteeBreast cancer patientsAfrican American raceAdvanced tumor stagePredictors of responseHigh nuclear gradeHigh tumor gradeNegative estrogen receptorNovel molecular predictorsPR negativity
2006
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
Yang CH, Gonzalez-Angulo AM, Reuben JM, Booser DJ, Pusztai L, Krishnamurthy S, Esseltine D, Stec J, Broglio KR, Islam R, Hortobagyi GN, Cristofanilli M. Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Annals Of Oncology 2006, 17: 813-817. PMID: 16403809, DOI: 10.1093/annonc/mdj131.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBone NeoplasmsBoronic AcidsBortezomibBreast NeoplasmsDisease ProgressionDisease-Free SurvivalFemaleHumansMaleMaximum Tolerated DoseMiddle AgedPleural NeoplasmsProtease InhibitorsPyrazinesReceptors, EstrogenReceptors, ProgesteroneSoft Tissue NeoplasmsSurvival RateTreatment OutcomeConceptsMetastatic breast cancerBreast cancerPlasma interleukin-6 levelsCommon grade 3Limited clinical activityClinical response ratePhase II studyInterleukin-6 levelsMedian survival timeWeek of restBroad antitumor activityStable diseaseII studyObjective responseSkin rashClinical effectsClinical benefitDisease progressionClinical activityGrade 3Pharmacodynamic dataSurvival timeMean inhibitionSingle agentResponse rateContinued Use of Trastuzumab (Herceptin) after Progression on Prior Trastuzumab Therapy in HER-2-Positive Metastatic Breast Cancer
Pusztai L, Esteva FJ. Continued Use of Trastuzumab (Herceptin) after Progression on Prior Trastuzumab Therapy in HER-2-Positive Metastatic Breast Cancer. Cancer Investigation 2006, 24: 187-191. PMID: 16619408, DOI: 10.1080/07357900500524629.Peer-Reviewed Original ResearchConceptsTrastuzumab therapyClinical trialsBreast cancerImportant unanswered clinical questionsLong-term side effectsContinuation of trastuzumabPrior trastuzumab therapyTrastuzumab-containing therapyUse of trastuzumabMetastatic breast cancerUnanswered clinical questionsPositive breast cancerRandomized clinical trialsTerm side effectsAccrue patientsMetastatic diseaseContinued administrationRandomized trialsControl armRegistry programDisease progressionClinical questionsSide effectsModest toxicityTrastuzumab
2005
Optimizing outcomes in HER2-positive breast cancer: the molecular rationale.
Esteva FJ, Pusztai L. Optimizing outcomes in HER2-positive breast cancer: the molecular rationale. Oncology 2005, 19: 5-16. PMID: 19364051.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCell ProliferationCombined Modality TherapyDisease ProgressionDrug Resistance, NeoplasmErbB ReceptorsFemaleGenetic TherapyHSP90 Heat-Shock ProteinsHumansProtein Kinase InhibitorsReceptor, ErbB-2TrastuzumabConceptsAnti-HER2 therapyHER2-positive breast cancerBreast cancerEpidermal growth factor receptor HER2Small molecule tyrosine kinase inhibitorsGrowth factor receptor HER2Common chemotherapy regimensSuppression of HER2Anti-HER2 agentsHER2-positive cancersStandard of careOverexpression of HER2Use of therapiesTyrosine kinase inhibitorsHER2 blockersChemotherapy regimensSequential regimensRandomized trialsMaximum antitumor effectMechanisms of resistanceClinical trialsOptimizing outcomesAntitumor effectsReceptor HER2HER2 activity
2003
Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer.
Rivera E, Valero V, Arun B, Royce M, Adinin R, Hoelzer K, Walters R, Wade JL, Pusztai L, Hortobagyi GN. Phase II study of pegylated liposomal doxorubicin in combination with gemcitabine in patients with metastatic breast cancer. Journal Of Clinical Oncology 2003, 21: 3249-54. PMID: 12947059, DOI: 10.1200/jco.2003.03.111.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerLiposomal doxorubicinBreast cancerOverall survivalDay 1Median cumulative anthracycline doseLeft ventricular ejection fractionPhase II clinical trialCommon grade 3Cumulative anthracycline doseFrequent nonhematologic toxicitiesPrevious anthracycline exposureHand-foot syndromeMedian overall survivalMedian response durationPhase II studyFront-line therapyVentricular ejection fractionOverall response rateAdjuvant chemotherapyAnthracycline doseAssessable patientsMeasurable diseaseNeutropenic complicationsNonhematologic toxicity
2002
Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer
Esteva FJ, Valero V, Booser D, Guerra LT, Murray JL, Pusztai L, Cristofanilli M, Arun B, Esmaeli B, Fritsche HA, Sneige N, Smith TL, Hortobagyi GN. Phase II Study of Weekly Docetaxel and Trastuzumab for Patients With HER-2–Overexpressing Metastatic Breast Cancer. Journal Of Clinical Oncology 2002, 20: 1800-1808. PMID: 11919237, DOI: 10.1200/jco.2002.07.058.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Agents, PhytogenicAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDisease ProgressionDocetaxelDrug Administration ScheduleFemaleGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceMiddle AgedPaclitaxelReceptor, ErbB-2TaxoidsTime FactorsTrastuzumabTreatment OutcomeUp-RegulationConceptsMetastatic breast cancerOverall response rateWeekly docetaxelBreast cancerPhase II studySecond-line therapyTrastuzumab-based therapyWeek of restExtracellular domain levelsII studyLoading doseMedian timeExcessive tearingFluid retentionECD concentrationsRepetitive dosingWeekly treatmentECD levelsPatientsTrastuzumabActive combinationResponse rateDocetaxelCancerAcute toxicity