2021
Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers
Li X, Kumar S, Harmanci A, Li S, Kitchen RR, Zhang Y, Wali VB, Reddy SM, Woodward WA, Reuben JM, Rozowsky J, Hatzis C, Ueno NT, Krishnamurthy S, Pusztai L, Gerstein M. Whole-genome sequencing of phenotypically distinct inflammatory breast cancers reveals similar genomic alterations to non-inflammatory breast cancers. Genome Medicine 2021, 13: 70. PMID: 33902690, PMCID: PMC8077918, DOI: 10.1186/s13073-021-00879-x.Peer-Reviewed Original ResearchConceptsSingle nucleotide variantsWhole-genome sequencingGermline single nucleotide variantsInternational Cancer Genome ConsortiumGenomic featuresGenomic alterationsGenome ConsortiumClonal architectureWhole Genomes (PCAWG) ConsortiumNon-coding regionsCancer-related pathwaysNon-IBC samplesCancer Genome Atlas ProgramMAST2 geneCopy number profilesPan-cancer analysisTGF-β pathwayGenomic architectureGenomic regionsSimilar genomic alterationsSimilar genomic characteristicsComplex SVsIBC samplesGenomic differencesOverall mutational load
2020
Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden
Qing T, Mohsen H, Marczyk M, Ye Y, O’Meara T, Zhao H, Townsend JP, Gerstein M, Hatzis C, Kluger Y, Pusztai L. Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden. Nature Communications 2020, 11: 2438. PMID: 32415133, PMCID: PMC7228928, DOI: 10.1038/s41467-020-16293-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overGerm-Line MutationHumansMiddle AgedNeoplasmsOpen Reading FramesSignal TransductionConceptsAge groupsGermline variantsSomatic mutationsLate-onset cancerEarly-onset cancersCancer hallmark genesSomatic mutation burdenMutation burdenMalignant transformationCancer genesYounger ageGermline alterationsCancerVariant burdenBurdenAverage numberHallmark genesAgeNegative correlationStrong negative correlationMutationsPatientsGroup
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 OutcomeEffects 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 deathOpen-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †
Gonzalez-Angulo AM, Akcakanat A, Liu S, Green MC, Murray JL, Chen H, Palla SL, Koenig KB, Brewster AM, Valero V, Ibrahim NK, Moulder-Thompson S, Litton JK, Tarco E, Moore J, Flores P, Crawford D, Dryden MJ, Symmans WF, Sahin A, Giordano SH, Pusztai L, Do K, Mills GB, Hortobagyi GN, Meric-Bernstam F. Open-label randomized clinical trial of standard neoadjuvant chemotherapy with paclitaxel followed by FEC versus the combination of paclitaxel and everolimus followed by FEC in women with triple receptor-negative breast cancer †. Annals Of Oncology 2014, 25: 1122-1127. PMID: 24669015, PMCID: PMC4037860, DOI: 10.1093/annonc/mdu124.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPathological complete responseStandard neoadjuvant chemotherapyNeoadjuvant chemotherapyReverse phase protein arrayBreast cancerPrimary triple-negative breast cancerMTOR pathwayReceptor-negative breast cancerTriple receptor-negative breast cancerAddition of everolimusGrade 3 pneumonitisGrade 3/4 stomatitisPI3K/AKT/mTOR pathwayRash/desquamationClinical response rateGrade 3/4 toxicitiesPhase II studyClinical end pointsCombination of paclitaxelAKT/mTOR pathwayDirect antiproliferative activityBreast cancer cellsDownregulation of mTORII studyMitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential
Pelicano H, Zhang W, Liu J, Hammoudi N, Dai J, Xu RH, Pusztai L, Huang P. Mitochondrial dysfunction in some triple-negative breast cancer cell lines: role of mTOR pathway and therapeutic potential. Breast Cancer Research 2014, 16: 434. PMID: 25209360, PMCID: PMC4303115, DOI: 10.1186/s13058-014-0434-6.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateCell Line, TumorElectron Transport Chain Complex ProteinsEnergy MetabolismFemaleGlucoseGlutathioneHumansHydrocarbons, BrominatedLactic AcidMitochondriaNADPOxidation-ReductionOxygen ConsumptionPropionatesReactive Oxygen SpeciesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneSignal TransductionTOR Serine-Threonine KinasesTriple Negative Breast NeoplasmsConceptsTNBC cellsBreast cancer cellsBreast cancerCancer cellsPositive cellsMetabolic alterationsIntroductionTriple-negative breast cancerMTOR pathwayEstrogen receptor-positive cellsER-positive cellsEffective therapeutic approachReceptor-positive cellsBreast cancer subtypesBreast cancer cell linesEffective therapeutic strategyTriple-negative breast cancer cell linesCurrent chemotherapeutic agentsMalignant breast cancerProfound metabolic alterationsHigher glucose uptakeInhibition of glycolysisCancer cell linesPoor prognosisLower mitochondrial respirationMitochondrial respiration
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 therapy
2012
Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers
Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L. Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Research And Treatment 2012, 134: 333-343. PMID: 22538770, PMCID: PMC3885980, DOI: 10.1007/s10549-012-2035-3.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancer subtypesBreast cancerPIK3CA mutationsCancer subtypesEstrogen receptor-positive cancersBreast cancer molecular subtypesMajor breast cancer subtypesSingle needle biopsyProspective clinical trialsReceptor-positive cancersDifferent breast cancer subtypesDifferent clinical subtypesNegative breast cancerCancer molecular subtypesFine-needle aspirationMutation patternsClinical subtypesClinical trialsNeedle biopsyMolecular subtypesNeedle aspirationInvestigational drugsStage IFBXW7 mutationsSeventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer
Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, Esteva FJ, Egan SE, Zacksenhaus E. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5832-5837. PMID: 22460789, PMCID: PMC3326451, DOI: 10.1073/pnas.1201105109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCalcium-Binding ProteinsCD24 AntigenCell DifferentiationCell DivisionEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsMiceNeoadjuvant TherapyNeoplastic Stem CellsPrognosisReceptor, ErbB-2Serrate-Jagged ProteinsSignal TransductionTrastuzumabTreatment OutcomeConceptsTumor-initiating cellsMammary tumor-initiating cellsBreast cancerClinical outcomesPrognostic signatureHuman epidermal growth factor receptorAnti-HER2 drugsAnti-HER2 therapyHigh-risk patientsHigh-risk subgroupsEpidermal growth factor receptorGrowth factor receptorBC cohortRisk patientsAggressive diseaseBC patientsRetrospective analysisImmune responsePrognostic powerTumor growthPatientsChemotherapyFactor receptorCancerFraction of cellsGene 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
2011
Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial
Hadad S, Iwamoto T, Jordan L, Purdie C, Bray S, Baker L, Jellema G, Deharo S, Hardie DG, Pusztai L, Moulder-Thompson S, Dewar JA, Thompson AM. Evidence for biological effects of metformin in operable breast cancer: a pre-operative, window-of-opportunity, randomized trial. Breast Cancer Research And Treatment 2011, 128: 783-794. PMID: 21655990, DOI: 10.1007/s10549-011-1612-1.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsCyclic Nucleotide Phosphodiesterases, Type 3FemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansHypoglycemic AgentsInsulinKi-67 AntigenMetforminMiddle AgedReproducibility of ResultsSignal TransductionTumor Suppressor Protein p53ConceptsTumor necrosis factor receptor 1Breast cancerCore biopsyPilot cohortOperable invasive breast cancerNon-diabetic womenOperable breast cancerInvasive breast cancerPrimary breast cancerEffect of metforminNecrosis factor receptor 1Serum insulin determinationsMessenger RNA expressionAnti-proliferative effectsFactor receptor 1Ingenuity Pathway AnalysisDiabetic womenMetformin 500Neoadjuvant chemotherapyControl patientsGastrointestinal upsetMetformin armSerum insulinTherapeutic trialsMetformin treatment
2010
Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer
Iwamoto T, Bianchini G, Booser D, Qi Y, Coutant C, Shiang CY, Santarpia L, Matsuoka J, Hortobagyi GN, Symmans WF, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Andre F, Simon R, Pusztai L. Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer. Journal Of The National Cancer Institute 2010, 103: 264-272. PMID: 21191116, DOI: 10.1093/jnci/djq524.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantConfounding Factors, EpidemiologicCytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemDatabases, GeneticDrug Resistance, NeoplasmFemaleGene Expression Regulation, NeoplasticGTP-Binding ProteinsHumansMiddle AgedNeoadjuvant TherapyNeoplasm StagingPredictive Value of TestsPrognosisReceptors, EstrogenSignal TransductionTreatment OutcomeConceptsER-negative breast cancerPathological complete responseER-positive cancersER-negative cancersBreast cancerChemotherapy responseComplete responseBetter prognosisChemotherapy sensitivityLymph node-negative breast cancerNode-negative breast cancerSystemic adjuvant therapyCell cycle-related gene setsBreast cancer subtypesIngenuity Pathway AnalysisAdjuvant therapyPreoperative chemotherapyPoor prognosisPooled analysisEstrogen receptorTreatment responseMolecular subtypesAdditional cohortPrognosisStage IDifferent gene expressions are associated with the different molecular subtypes of inflammatory breast cancer
Iwamoto T, Bianchini G, Qi Y, Cristofanilli M, Lucci A, Woodward WA, Reuben JM, Matsuoka J, Gong Y, Krishnamurthy S, Valero V, Hortobagyi GN, Robertson F, Symmans WF, Pusztai L, Ueno NT. Different gene expressions are associated with the different molecular subtypes of inflammatory breast cancer. Breast Cancer Research And Treatment 2010, 125: 785-795. PMID: 21153052, PMCID: PMC4109066, DOI: 10.1007/s10549-010-1280-6.Peer-Reviewed Original ResearchConceptsInflammatory breast cancerClinical subtypesBreast cancerNon-IBC patientsCase-control studyDistinct clinical subtypesDifferent molecular subtypesNon-IBC tumorsSignificant differencesNon-IBC specimensImmune system-related pathwaysLipid metabolism-related pathwaysHER2 statusReceptor phenotypeMetabolism-related pathwaysMolecular subtypesIBC tumorsSurvival curvesSubtypesTumor samplesHormone receptorsCancerPatientsT-testHER2PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer
Loi S, Haibe-Kains B, Majjaj S, Lallemand F, Durbecq V, Larsimont D, Gonzalez-Angulo AM, Pusztai L, Symmans WF, Bardelli A, Ellis P, Tutt AN, Gillett CE, Hennessy BT, Mills GB, Phillips WA, Piccart MJ, Speed TP, McArthur GA, Sotiriou C. PIK3CA mutations associated with gene signature of low mTORC1 signaling and better outcomes in estrogen receptor–positive breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 10208-10213. PMID: 20479250, PMCID: PMC2890442, DOI: 10.1073/pnas.0907011107.Peer-Reviewed Original ResearchMeSH KeywordsAntibiotics, AntineoplasticAntineoplastic Agents, HormonalBase SequenceBreast NeoplasmsCell Line, TumorClass I Phosphatidylinositol 3-KinasesDNA PrimersFemaleGene Expression ProfilingHumansMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesMutationNeoplasms, Hormone-DependentOligonucleotide Array Sequence AnalysisPhosphatidylinositol 3-KinasesPrognosisProteinsProto-Oncogene Proteins c-aktReceptor, ErbB-2Receptors, EstrogenSignal TransductionSirolimusTamoxifenTOR Serine-Threonine KinasesTranscription FactorsConceptsBreast cancerPIK3CA mutationsClinical outcomesEstrogen receptor-positive breast cancerReceptor-positive breast cancerGene signaturePIK3CA mutation statusPI3K/mTOR inhibitorBetter clinical outcomesPI3K/mTOR inhibitionHuman breast cancerBC cell linesPIK3CA mutant breast cancersCommon genetic aberrationsTamoxifen monotherapyBetter prognosisMTOR inhibitorsBetter outcomesMutation statusMTOR inhibitionPathway activationExperimental modelGenetic aberrationsPrognosisCell lines
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 numberInhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis
Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, Feig B, Zhang W, Pusztai L, Symmans WF, Wu Y, Arlinghaus RB. Inhibition of Lipocalin 2 Impairs Breast Tumorigenesis and Metastasis. Cancer Research 2009, 69: 8579-8584. PMID: 19887608, DOI: 10.1158/0008-5472.can-09-1934.Peer-Reviewed Original ResearchMeSH KeywordsAcute-Phase ProteinsAnimalsBlotting, WesternBreast NeoplasmsCell Line, TumorFemaleFlow CytometryGene Expression Regulation, NeoplasticHumansImmunohistochemistryLipocalin-2LipocalinsMatrix Metalloproteinase 9MiceMice, KnockoutNeoplasm InvasivenessNF-kappa BOncogene ProteinsReceptor, ErbB-2Reverse Transcriptase Polymerase Chain ReactionSignal TransductionConceptsLCN2 expressionBreast cancerBreast tumorigenesisMatrix metalloproteinase-9 activityTumor formationMammary tumor mouse modelMammary tumor formationMetalloproteinase-9 activityMatrix metalloproteinase-9Breast cancer therapyTumor mouse modelBreast tumor formationAkt/NFBreast cancer cellsMurine breast tumorsInhibitory monoclonal antibodiesLCN2 functionsLung metastasesLipocalin-2Metalloproteinase-9Mouse modelAggressive typeBreast tumorsKappaB pathwayMetastasis
2008
Evaluation of biological pathways involved in chemotherapy response in breast cancer
Tordai A, Wang J, Andre F, Liedtke C, Yan K, Sotiriou C, Hortobagyi GN, Symmans WF, Pusztai L. Evaluation of biological pathways involved in chemotherapy response in breast cancer. Breast Cancer Research 2008, 10: r37. PMID: 18445275, PMCID: PMC2397539, DOI: 10.1186/bcr2088.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDoxorubicinDrug Resistance, NeoplasmE2F3 Transcription FactorFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, p53HumansKi-67 AntigenLymphatic MetastasisMiddle AgedMutationNeoadjuvant TherapyNeoplasm StagingPaclitaxelReceptors, EstrogenSignal TransductionTreatment OutcomeConceptsER-positive breast cancerPathologic complete responseER-positive cancersER-negative cancersGenomic grade indexBreast cancerChemotherapy sensitivityGene signatureER-negative breast cancerProliferation signatureER-positive patientsPositive breast cancerExpression of ERPreoperative paclitaxelProliferation gene signatureCyclophosphamide chemotherapyComplete responseResidual cancerChemotherapy responsePCR groupKi67 expressionEstrogen receptorIntroductionOur goalCancerChemotherapy
2007
CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer
Esteva FJ, Wang J, Lin F, Mejia JA, Yan K, Altundag K, Valero V, Buzdar AU, Hortobagyi GN, Symmans WF, Pusztai L. CD40 signaling predicts response to preoperative trastuzumab and concomitant paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in HER-2-overexpressing breast cancer. Breast Cancer Research 2007, 9: r87. PMID: 18086299, PMCID: PMC2246190, DOI: 10.1186/bcr1836.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, Fine-NeedleBreast NeoplasmsCD40 AntigensCyclophosphamideEpirubicinFemaleFluorouracilGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMastectomyMastectomy, Modified RadicalMastectomy, SegmentalMiddle AgedNeoadjuvant TherapyNeoplasm StagingNeoplasm, ResidualPaclitaxelPredictive Value of TestsReceptor, ErbB-2RNA, MessengerSignal TransductionTranscription, GeneticTrastuzumabTreatment OutcomeUp-RegulationConceptsPathologic complete responseBreast cancerIIIA breast cancerFine-needle aspirationConcomitant paclitaxelConcomitant trastuzumabFEC therapyPreoperative trastuzumabPreoperative chemotherapyPrimary endpointComplete responseNodal statusResidual cancerTumor sizeTumor responseNuclear gradeReceptor mRNAMolecular predictorsTrastuzumabStage IIGreater riskLow expressionCancerCyclophosphamidePatients
2005
The Nuclear Transcription Factor κB/bcl-2 Pathway Correlates with Pathologic Complete Response to Doxorubicin-Based Neoadjuvant Chemotherapy in Human Breast Cancer
Buchholz TA, Garg AK, Chakravarti N, Aggarwal BB, Esteva FJ, Kuerer HM, Singletary SE, Hortobagyi GN, Pusztai L, Cristofanilli M, Sahin AA. The Nuclear Transcription Factor κB/bcl-2 Pathway Correlates with Pathologic Complete Response to Doxorubicin-Based Neoadjuvant Chemotherapy in Human Breast Cancer. Clinical Cancer Research 2005, 11: 8398-8402. PMID: 16322301, DOI: 10.1158/1078-0432.ccr-05-0885.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBcl-2-Associated X ProteinBreast NeoplasmsCell NucleusChemotherapy, AdjuvantCyclophosphamideCytoplasmDoxorubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm StagingNF-kappa BProto-Oncogene Proteins c-bcl-2Signal TransductionSurvival RateTreatment OutcomeConceptsPathologic complete responseHuman breast cancerNF-kappaBNeoadjuvant chemotherapyComplete responseNeoadjuvant doxorubicinBcl-2Poor responseBreast cancerAnthracycline-based neoadjuvant chemotherapyNF-kappaB.Bcl-2-positive tumorsHuman breast cancer samplesBreast cancer responseClinical outcome dataTranscription factor NF-kappaBBreast cancer pathologistNuclear factor-kappaBBreast cancer samplesPCR ratePositive tumorsChemotherapy responseTumor stainingImmunohistochemical stainingCancer response