2023
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Licata L, Barreca M, Galbardi B, Dugo M, Viale G, Győrffy B, Karn T, Pusztai L, Gianni L, Callari M, Bianchini G. Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy. British Journal Of Cancer 2023, 129: 2025-2033. PMID: 37935787, PMCID: PMC10703787, DOI: 10.1038/s41416-023-02477-7.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkersBreast NeoplasmsCell ProliferationCyclinsDisease-Free SurvivalFemaleHumansNeoadjuvant TherapyPrognosisConceptsNeoadjuvant chemotherapyPoor prognosisBreast cancerTreatment responseHigher pathological complete response rateResponse rateHigh pathological response ratePathological complete response ratePathological response rateComplete response rateHigher proliferationHigh recurrence riskMolecular featuresEndocrine therapyLower ERHigh TMBDismal outcomePIK3CA mutationsMethodsGene expression dataClinical dataT cellsPotential therapyRecurrence riskTumorsUnique molecular features
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
Identification 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
2017
Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer
Wali VB, Langdon CG, Held MA, Platt JT, Patwardhan GA, Safonov A, Aktas B, Pusztai L, Stern DF, Hatzis C. Systematic Drug Screening Identifies Tractable Targeted Combination Therapies in Triple-Negative Breast Cancer. Cancer Research 2017, 77: 566-578. PMID: 27872098, PMCID: PMC5582957, DOI: 10.1158/0008-5472.can-16-1901.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTNBC cell linesPairwise drug combinationsClinical translationAggressive diseaseCombination therapyBreast cancerPreclinical proofDrug combinationsCombination treatmentInvestigational drugsSingle agentSensitivity patternCell sensitivityCell linesTherapyApoptotic activityAnticancer activityDownregulated genesMitogenic signalingCrizotinibBlockadeClinicAgentsCancer
2014
Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer
Fuentes-Mattei E, Velazquez-Torres G, Phan L, Zhang F, Chou PC, Shin JH, Choi HH, Chen JS, Zhao R, Chen J, Gully C, Carlock C, Qi Y, Zhang Y, Wu Y, Esteva FJ, Luo Y, McKeehan WL, Ensor J, Hortobagyi GN, Pusztai L, Symmans W, Lee MH, Yeung SC. Effects of Obesity on Transcriptomic Changes and Cancer Hallmarks in Estrogen Receptor–Positive Breast Cancer. Journal Of The National Cancer Institute 2014, 106: dju158. PMID: 24957076, PMCID: PMC4110474, DOI: 10.1093/jnci/dju158.Peer-Reviewed Original ResearchMeSH KeywordsAdipocytesAdipokinesAgedAnimalsAntineoplastic AgentsBiomarkers, TumorBreast NeoplasmsCell ProliferationDisease Models, AnimalEverolimusFemaleHumansKaplan-Meier EstimateMetforminMiceMice, TransgenicMiddle AgedObesityPostmenopauseProspective StudiesProto-Oncogene Proteins c-aktReceptors, EstrogenSignal TransductionSirolimusTOR Serine-Threonine KinasesTranscriptomeConceptsEstrogen receptor-positive breast cancerReceptor-positive breast cancerBreast cancer cell proliferationEffect of obesityBreast cancer patientsObese mouse modelAdipocyte-secreted adipokineCancer cell proliferationCancer patientsBreast cancerMouse modelCell proliferationAssociation of obesityAkt/mTOR activationMammary tumor growthEpithelial-mesenchymal transition genesAKT/mTOR pathwayBreast cancer aggressivenessBreast tumor formationCancer hallmarksPostmenopausal womenPretreatment biopsiesProspective cohortAdipokine secretionCancer death
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 propertiesProliferation 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 therapyA 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories
Szekely B, Iwamoto T, Szasz AM, Qi Y, Matsuoka J, Symmans WF, Tokes AM, Kulka J, Swanton C, Pusztai L. A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. Breast Cancer Research And Treatment 2013, 138: 691-698. PMID: 23504136, DOI: 10.1007/s10549-013-2475-4.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmBreast NeoplasmsCell ProliferationChemotherapy, AdjuvantCohort StudiesDatabases, GeneticDNA Topoisomerases, Type IIDNA-Binding ProteinsFemaleForkhead Box Protein M1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticGenome, HumanHumansKi-67 AntigenPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsPrognosisReceptors, EstrogenSurvival RateTamoxifenConceptsGenomic grade indexGrade 2 cancersPrognostic valueProliferation scoreBreast cancerDistant metastasis-free survival curvesGrade 2Metastasis-free survival curvesER-positive breast cancerSystemic adjuvant therapyHigh expressionCohort of patientsHistological grade 2Intermediate-risk cancerPositive breast cancerSimilar prognostic valueGrade 2 tumorsHigh-risk groupGrade 1 cancersHistological grade groupsNon-significant trendWorse DMFSAdjuvant tamoxifenAdjuvant therapyWorse survival
2012
Gene Expression, Molecular Class Changes, and Pathway Analysis after Neoadjuvant Systemic Therapy for Breast Cancer
Gonzalez-Angulo AM, Iwamoto T, Liu S, Chen H, Do KA, Hortobagyi GN, Mills GB, Meric-Bernstam F, Symmans WF, Pusztai L. Gene Expression, Molecular Class Changes, and Pathway Analysis after Neoadjuvant Systemic Therapy for Breast Cancer. Clinical Cancer Research 2012, 18: 1109-1119. PMID: 22235097, PMCID: PMC3288822, DOI: 10.1158/1078-0432.ccr-11-2762.Peer-Reviewed Original ResearchConceptsResidual cancerBreast cancerAdjuvant treatment strategiesNeoadjuvant systemic therapyLike breast cancerBasal-like cancersSmall G proteinsCalmodulin-dependent protein kinase IICancer stem cell signaturesEnergy metabolismFine-needle aspiration specimensGene expression differencesEpithelial-mesenchymal transitionSonic hedgehog (Shh) signalingNeedle aspiration specimensProtein kinase IIImmune-related pathwaysNew therapeutic insightsGene expression dataStem cell signatureSonic hedgehog pathwaySystemic therapy
2009
Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate
Shiang CY, Qi Y, Wang B, Lazar V, Wang J, Fraser Symmans W, Hortobagyi GN, Andre F, Pusztai L. Amplification of fibroblast growth factor receptor-1 in breast cancer and the effects of brivanib alaninate. Breast Cancer Research And Treatment 2009, 123: 747-755. PMID: 20024612, DOI: 10.1007/s10549-009-0677-6.Peer-Reviewed Original ResearchMeSH KeywordsAlanineAntineoplastic AgentsBreast NeoplasmsCell Line, TumorCell ProliferationComparative Genomic HybridizationDose-Response Relationship, DrugFemaleFibroblast Growth Factor 2Gene AmplificationGene DosageGene Expression ProfilingGene Expression Regulation, NeoplasticHumansInhibitory Concentration 50Mitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProto-Oncogene Proteins c-aktReceptor, Fibroblast Growth Factor, Type 1RNA, MessengerSignal TransductionTriazinesConceptsFibroblast growth factor receptor 1Growth factor receptor 1Breast cancer cell linesBreast cancerFactor receptor 1Cancer cell linesKinase activityProtein overexpressionReceptor 1Cell linesCopy numberDirect anti-proliferative effectsGene expression profilingHuman breast cancerTyrosine kinase activityAnti-angiogenic effectsMDA-MB-361Small molecule inhibitorsAnti-proliferative effectsGrowth inhibitionDNA copy numberProtein expression levelsBrivanib treatmentFGFR-1 mRNANormal copy number
2008
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Garber JE, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski J. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer. Journal Of Clinical Oncology 2008, 26: 806-813. PMID: 18258990, DOI: 10.1200/jco.2007.15.2983.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic AgentsApoptosisBiomarkersBiomedical ResearchBreast NeoplasmsCell ProliferationEpidemiologic Research DesignErbB ReceptorsEthics, ClinicalFemaleGene Expression ProfilingHumansMastectomy, SegmentalNeoadjuvant TherapyPatient AdvocacyPreoperative CarePrognosisReceptors, SteroidTreatment OutcomeConceptsPreoperative systemic therapyOperable breast cancerSystemic therapyBreast cancerTrial designEnd pointCohesive multidisciplinary teamBreast conservation ratesEffective alternative therapyTrial end pointsLong-term outcomesSpecific breast cancer subtypesPredictors of responseNovel trial designsIntermediate end pointsBreast cancer subtypesIndividual patient subgroupsAdjuvant trialsPatient subgroupsSmall trialsAlternative therapiesMAIN OUTCOMEClinical careCancer subtypesMultidisciplinary team
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