2023
De Novo Oligometastatic Breast Cancer
Pusztai L, Rozenblit M, Dubsky P, Bachelot T, Kirby A, Linderholm B, White J, Chmura S, Carey L, Chua B, Miller K. De Novo Oligometastatic Breast Cancer. Journal Of Clinical Oncology 2023, 41: 5237-5241. PMID: 37607325, PMCID: PMC10691789, DOI: 10.1200/jco.23.00911.Peer-Reviewed Original Research
2022
CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression
Zhang M, Liu ZZ, Aoshima K, Cai WL, Sun H, Xu T, Zhang Y, An Y, Chen JF, Chan LH, Aoshima A, Lang SM, Tang Z, Che X, Li Y, Rutter SJ, Bossuyt V, Chen X, Morrow JS, Pusztai L, Rimm DL, Yin M, Yan Q. CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression. Science Translational Medicine 2022, 14: eabf5473. PMID: 35108062, PMCID: PMC9003667, DOI: 10.1126/scitranslmed.abf5473.Peer-Reviewed Original ResearchConceptsBreast cancer metastasisReticuloendotheliosis viral oncogene homolog ACancer metastasisImmune suppressionM2 macrophagesWorse metastasis-free survivalMetastatic breast cancerMetastasis-free survivalV-rel avian reticuloendotheliosis viral oncogene homolog ACancer-related deathPrimary breast tumorsMultiple mouse modelsNF-κB signalingImmunocompetent settingNuclear factor-κB family membersMetastasis-promoting genesDistant metastasisMetastatic sitesPrimary tumorEffective therapyBreast cancerMetastasis treatmentMouse modelBreast tumorsMetastasis
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
Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers
Rozenblit M, Huang R, Danziger N, Hegde P, Alexander B, Ramkissoon S, Blenman K, Ross JS, Rimm DL, Pusztai L. Comparison of PD-L1 protein expression between primary tumors and metastatic lesions in triple negative breast cancers. Journal For ImmunoTherapy Of Cancer 2020, 8: e001558. PMID: 33239417, PMCID: PMC7689582, DOI: 10.1136/jitc-2020-001558.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenFemaleHumansMiddle AgedNeoplasm MetastasisRetrospective StudiesTriple Negative Breast NeoplasmsConceptsPD-L1 positivity ratePD-L1 positivityPD-L1 expressionDifferent metastatic sitesPrimary tumorMetastatic sitesPositivity rateImmune cellsMetastatic lesionsTumor cellsPD-L1 protein expressionTriple-negative breast cancerMore primary tumorsTriple negative breast cancer tumorsPrimary breast lesionsPrimary outcome measureSoft tissueNegative breast cancerLow positivity rateBreast cancer tumorsBone metastasesFoundation MedicineLymph nodesPD-L1Spearman correlation coefficientOverall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis
Schettini F, Giudici F, Giuliano M, Cristofanilli M, Arpino G, Del Mastro L, Puglisi F, De Placido S, Paris I, De Placido P, Venturini S, De Laurentis M, Conte P, Juric D, Llombart-Cussac A, Pusztai L, Prat A, Jerusalem G, Di Leo A, Generali D. Overall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis. Journal Of The National Cancer Institute 2020, 112: 1089-1097. PMID: 32407488, PMCID: PMC7669227, DOI: 10.1093/jnci/djaa071.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6FemaleHumansLetrozoleNeoplasm MetastasisPiperazinesProtein Kinase InhibitorsPyridinesRandomized Controlled Trials as TopicConceptsSecond-line therapyMetastatic breast cancerEndocrine therapyCDK4/6 inhibitorsVisceral involvementBreast cancerPostmenopausal metastatic breast cancerAvailable phase IIChemotherapy-naïve patientsClear OS benefitSpecific clinical subgroupsProgression-free survivalOverall survival dataBreast cancer prognosisStudy-level factorsCyclin-dependent kinase 4Random-effects modelSystematic literature searchEndocrine monotherapyOS benefitOS independentOverall survivalUpfront therapyMenopausal statusMetastatic sites
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 ResearchImmunotherapy and targeted therapy combinations in metastatic breast cancer
Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. The Lancet Oncology 2019, 20: e175-e186. PMID: 30842061, DOI: 10.1016/s1470-2045(19)30026-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerImmune checkpoint inhibitorsTumor-infiltrating lymphocytesDeath ligand 1Most breast cancersNew treatment modalitiesSingle-drug therapyCyclin-dependent kinase 4Development of combinationsCheckpoint inhibitorsEndocrine therapyDeath-1Immunotherapeutic approachesBiological therapyTherapy combinationsTreatment modalitiesLittle efficacyImmune evasionAngiogenesis inhibitorsTherapyImmunotherapyCancerPolymerase inhibitorsMonoclonal antibodies
2017
Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer
Chung JH, Pavlick D, Hartmaier R, Schrock AB, Young L, Forcier B, Ye P, Levin MK, Goldberg M, Burris H, Gay LM, Hoffman AD, Stephens PJ, Frampton GM, Lipson DM, Nguyen DM, Ganesan S, Park BH, Vahdat LT, Leyland-Jones B, Mughal TI, Pusztai L, O’Shaughnessy J, Miller VA, Ross JS, Ali SM. Hybrid capture-based genomic profiling of circulating tumor DNA from patients with estrogen receptor-positive metastatic breast cancer. Annals Of Oncology 2017, 28: 2866-2873. PMID: 28945887, PMCID: PMC5834148, DOI: 10.1093/annonc/mdx490.Peer-Reviewed Original ResearchConceptsEstrogen receptor-positive metastatic breast cancerMetastatic breast cancerBreast cancerGenomic profilingGenomic alterationsEstrogen receptor-positive breast cancerMetastatic breast cancer managementReceptor-positive breast cancerTumor DNACo-occurring genomic alterationsMetastatic tissue biopsiesTissue samplesRoutine clinical careBreast cancer managementCourse of diseasePeripheral blood samplesMetastatic tumor tissueMetastatic diseaseFemale patientsInvasive alternativeCtDNA fractionCancer managementClinical careBlood samplesPatientsPhylogenetic 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
Characterization of DNA variants in the human kinome in breast cancer
Agarwal D, Qi Y, Jiang T, Liu X, Shi W, Wali VB, Turk B, Ross JS, Fraser Symmans W, Pusztai L, Hatzis C. Characterization of DNA variants in the human kinome in breast cancer. Scientific Reports 2015, 5: 14736. PMID: 26420498, PMCID: PMC4588561, DOI: 10.1038/srep14736.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsFemaleGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenetic VariationHigh-Throughput Nucleotide SequencingHumansMiddle AgedMutationNeoplasm GradingNeoplasm MetastasisNeoplasm StagingPhosphotransferasesPolymorphism, Single NucleotideReproducibility of ResultsTranscriptomeConceptsBreast cancerHuman kinomeKinase geneGreater mutational loadNucleic acid variationPrimary cancer samplesPrimary breast cancerHistologic grade 1Major functional impactSOLiD sequencing platformIndividual breast cancersNon-synonymous variantsFine-needle biopsyGrade 3 casesCancer-related genesNucleotide variationsDNA variantsSequencing platformsMetastatic lesionsMutational loadAcid variationsCancer biologyGenesNeedle biopsyAdditional cancers
2014
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, Fend L, Hannani D, Aymeric L, Ma Y, Niso-Santano M, Kepp O, Schultze JL, Tüting T, Belardelli F, Bracci L, La Sorsa V, Ziccheddu G, Sestili P, Urbani F, Delorenzi M, Lacroix-Triki M, Quidville V, Conforti R, Spano JP, Pusztai L, Poirier-Colame V, Delaloge S, Penault-Llorca F, Ladoire S, Arnould L, Cyrta J, Dessoliers MC, Eggermont A, Bianchi ME, Pittet M, Engblom C, Pfirschke C, Préville X, Uzè G, Schreiber RD, Chow MT, Smyth MJ, Proietti E, André F, Kroemer G, Zitvogel L. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nature Medicine 2014, 20: 1301-1309. PMID: 25344738, DOI: 10.1038/nm.3708.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsAnthracyclinesBreast NeoplasmsChemokine CXCL10DoxorubicinFemaleGene Expression Regulation, NeoplasticHumansImmunocompetenceInterferon Type IMice, Inbred C57BLMyxovirus Resistance ProteinsNeoadjuvant TherapyNeoplasm MetastasisReceptor, Interferon alpha-betaReceptors, Pattern RecognitionRNARNA, MessengerSignal TransductionToll-Like Receptor 3Treatment OutcomeGene 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
2013
Proliferation 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 therapy
2010
Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor‐positive, HER2‐normal, grade II, lymph node‐negative breast cancers
Kelly CM, Krishnamurthy S, Bianchini G, Litton JK, Gonzalez‐Angulo A, Hortobagyi GN, Pusztai L. Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor‐positive, HER2‐normal, grade II, lymph node‐negative breast cancers. Cancer 2010, 116: 5161-5167. PMID: 20665886, DOI: 10.1002/cncr.25269.Peer-Reviewed Original ResearchConceptsTrial Assigning Individualized OptionsRisk of recurrenceOncotype DXRecurrence scoreBreast cancerIntermediate riskGrade I/II tumorsLymph node-negative breast cancerNode-negative breast cancerStage I/IID. Anderson Cancer CenterOncotype DX breast cancerRisk estimatesIntermediate-risk populationEarly breast cancerRoutine clinical variablesHigh-risk groupOncotype DX testingAnderson Cancer CenterAdjuvant chemotherapyDistant recurrenceConsecutive patientsII tumorsClinicopathological variablesLobular carcinomaEstrogen and HER-2 Receptor Discordance Between Primary Breast Cancer and Metastasis
Pusztai L, Viale G, Kelly CM, Hudis CA. Estrogen and HER-2 Receptor Discordance Between Primary Breast Cancer and Metastasis. The Oncologist 2010, 15: 1164-1168. PMID: 21041379, PMCID: PMC3227913, DOI: 10.1634/theoncologist.2010-0059.Peer-Reviewed Original ResearchConceptsReceptors resultsBreast cancerHuman epidermal growth factor receptor 2 receptor statusRepeat tumor biopsiesRoutine repeat biopsyPrimary breast cancerReceptor-positive cancersReceptor-negative cancersEndocrine therapyFalse-negative resultsReceptor discordanceMetastatic diseaseReceptor statusRepeat biopsyClinical courseRecurrent cancerClinical groundsPrimary tumorTumor nestsEstrogen receptorTumor biopsiesHormone responsivenessReceptor assayCancerDiscordant resultsStability 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 conversionTumorsPatientsMetastasisTherapyEstrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials
Andre F, Broglio K, Pusztai L, Berrada N, Mackey JR, Nabholtz JM, Chan S, Hortobagyi GN. Estrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials. The Oncologist 2010, 15: 476-483. PMID: 20421265, PMCID: PMC3227977, DOI: 10.1634/theoncologist.2009-0150.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerEfficacy of docetaxelBreast cancerHigh response rateER expressionResponse rateEstrogen receptorHazard ratioRandomized trialsDisease progressionProgression-free survival timeCox proportional hazards modelDocetaxel-based regimenEstrogen receptor expressionProportional hazards modelEffect of docetaxelER- diseasePFS timeDocetaxel efficacyPooled analysisTumor responseReceptor expressionSurvival timeLower riskHazards model
2009
CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence
Andre F, Xia W, Conforti R, Wei Y, Boulet T, Tomasic G, Spielmann M, Zoubir M, Berrada N, Arriagada R, Hortobagyi GN, Hung M, Pusztai L, Delaloge S, Michiels S, Cristofanilli M. CXCR4 Expression in Early Breast Cancer and Risk of Distant Recurrence. The Oncologist 2009, 14: 1182-1188. PMID: 19939894, DOI: 10.1634/theoncologist.2009-0161.Peer-Reviewed Original ResearchConceptsPrimary breast tumorsCXCR4 expressionBone metastasesBreast tumorsClinical characteristicsDistant metastasisPrognostic valueHigh riskLigand stromal cell-derived factor-1Stromal cell-derived factor-1Cell-derived factor-1Bone-targeted agentsEarly breast cancerProspective clinical trialsCox regression modelNovel adjuvant strategyExpression of CXCR4Chemokine receptor 4Early metastatic processOccurrence of metastasesSpecific organ sitesCXCR4 tumorsDistant recurrenceOverall survivalAdjuvant strategiesMetastatic gene signatures and emerging novel prognostic tests in the management of early stage breast cancer
Tordai A, Liedtke C, Pusztai L. Metastatic gene signatures and emerging novel prognostic tests in the management of early stage breast cancer. Clinical & Experimental Metastasis 2009, 26: 625-632. PMID: 19381845, DOI: 10.1007/s10585-009-9261-z.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsEarly DiagnosisGene Expression ProfilingHumansNeoplasm MetastasisOligonucleotide Array Sequence AnalysisPrognosisConceptsMetastatic gene signatureGene expression studiesGene expression profilingDistinct neoplastic diseasesExpression profilingDNA microarraysExpression studiesGene expressionMRNA transcriptsGene signatureSingle experimentNovel diagnostic assaysTranscriptsDiagnostic assaysNovel prognostic testsMicroarrayProfilingExpression