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 ResearchConceptsNeoadjuvant 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
2021
Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial
Paoletti C, Barlow WE, Cobain EF, Bergqvist M, Mehta RS, Gralow JR, Hortobagyi GN, Albain KS, Pusztai L, Sharma P, Godwin AK, Thompson AM, Hayes DF, Rae JM. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial. Clinical Cancer Research 2021, 27: clincanres.1562.2021. PMID: 34521624, PMCID: PMC8595696, DOI: 10.1158/1078-0432.ccr-21-1562.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicFemaleHumansKaplan-Meier EstimateMiddle AgedPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesThymidine KinaseTreatment OutcomeConceptsProgression-free survivalMetastatic breast cancerFirst-line endocrine therapyOverall survivalEndocrine therapyHormone receptor-positive metastatic breast cancer patientsHormone receptor-positive metastatic breast cancerPositive metastatic breast cancer patientsSubsequent progression-free survivalMetastatic breast cancer patientsWorse progression-free survivalCombination endocrine therapySerum thymidine kinase 1Trial of anastrozoleThymidine kinase 1 activityBreast cancer patientsLog-rank testLine endocrine therapyDu/LAdjuvant tamoxifenPrognostic effectCox regressionPoor prognosisWorse prognosisKaplan-Meier
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 increases
2017
Association Between Genomic Metrics and Immune Infiltration in Triple-Negative Breast Cancer
Karn T, Jiang T, Hatzis C, Sänger N, El-Balat A, Rody A, Holtrich U, Becker S, Bianchini G, Pusztai L. Association Between Genomic Metrics and Immune Infiltration in Triple-Negative Breast Cancer. JAMA Oncology 2017, 3: 1707-1711. PMID: 28750120, PMCID: PMC5824276, DOI: 10.1001/jamaoncol.2017.2140.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCohort StudiesGene DosageGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic HeterogeneityHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingPrognosisSequence Analysis, DNASequence Analysis, RNASurvival AnalysisTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerImmune infiltrationTNBC cohortBetter prognosisPrognostic categoriesPoor prognosisInverse associationBreast cancerImmune surveillanceImmune checkpoint inhibitor therapyMore effective immunotherapy strategiesSubset of TNBCLow immune cell infiltrationClonal heterogeneityCheckpoint inhibitor therapySelection of patientsImmune cell infiltrationEffective immunotherapy strategiesIndependent validation cohortPatient survival informationLymphocyte countImmunotherapy strategiesInhibitor therapyNeoantigen loadValidation cohort
2014
Mitochondrial 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
DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes
Santarpia L, Iwamoto T, Di Leo A, Hayashi N, Bottai G, Stampfer M, André F, Turner NC, Symmans WF, Hortobágyi GN, Pusztai L, Bianchini G. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes. The Oncologist 2013, 18: 1063-1073. PMID: 24072219, PMCID: PMC3805146, DOI: 10.1634/theoncologist.2013-0163.Peer-Reviewed Original ResearchConceptsResidual invasive cancerHER2-negative tumorsInvasive cancerER-positive/HER2-negative tumorsPredictive valueUntreated breast cancer patientsAffymetrix gene expression profilesHER2-negative subgroupMolecular breast cancer subtypesTaxane/anthracyclinePathological complete responseER-positive tumorsAnthracycline-treated patientsHER2-positive tumorsBreast cancer patientsER-negative tumorsBreast cancer subtypesAnthracycline regimensComplete responseBetter prognosisClinical outcomesBC patientsPoor prognosisPredictive factorsPrognostic valueDeveloping Safety Criteria for Introducing New Agents into Neoadjuvant Trials
DeMichele A, Berry DA, Zujewski J, Hunsberger S, Rubinstein L, Tomaszewski JE, Kelloff G, Perlmutter J, Buxton M, Lyandres J, Albain KS, Benz C, Chien AJ, Haluska P, Leyland-Jones B, Liu MC, Munster P, Olopade O, Park JW, Parker BA, Pusztai L, Tripathy D, Rugo H, Yee D, Esserman L. Developing Safety Criteria for Introducing New Agents into Neoadjuvant Trials. Clinical Cancer Research 2013, 19: 2817-2823. PMID: 23470967, PMCID: PMC4096560, DOI: 10.1158/1078-0432.ccr-12-2620.Peer-Reviewed Original ResearchConceptsNeoadjuvant trialsNeoadjuvant settingStandard therapyInvestigational agentsDrug developmentPhase II neoadjuvant trialI-SPY2 trialSafe drug developmentShort-term endpointsNeoadjuvant studiesCurable patientsPathologic responsePoor prognosisNovel therapiesBreast cancerNovel agentsSafety dataStudy populationDisease processEfficacious drugsNew agentsDrug AdministrationPatient exposurePatient safetyStudy designComparison of molecular subtype distribution in triple-negative inflammatory and non-inflammatory breast cancers
Masuda H, Baggerly KA, Wang Y, Iwamoto T, Brewer T, Pusztai L, Kai K, Kogawa T, Finetti P, Birnbaum D, Dirix L, Woodward WA, Reuben JM, Krishnamurthy S, Symmans W, Van Laere SJ, Bertucci F, Hortobagyi GN, Ueno NT. Comparison of molecular subtype distribution in triple-negative inflammatory and non-inflammatory breast cancers. Breast Cancer Research 2013, 15: r112. PMID: 24274653, PMCID: PMC3978878, DOI: 10.1186/bcr3579.Peer-Reviewed Original ResearchConceptsInflammatory breast cancerTriple-negative breast cancerTN-IBCIBC statusTNBC subtypesBreast cancerTNBC cohortClinical outcomesNon-inflammatory breast cancerMolecular subtype distributionWorld IBC ConsortiumRecurrence-free survivalNon-inflammatory typeClinical characteristicsOverall survivalPoor prognosisClinical behaviorSubtype distributionConclusionsOur dataHeterogeneous diseaseSubtypesCancerSignificant predictorsGene expression profilesCohort
2012
172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups
Iwamoto T, Pusztai L, Matsuoka J, Callari M, Kelly C, Qi Y, Motoki T, Taira N, Santarpia L, Doihara H, Gianni L, Bianchini G. 172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups. Annals Of Oncology 2012, 23: ix74-ix75. DOI: 10.1016/s0923-7534(20)32783-6.Peer-Reviewed Original ResearchPathologic complete responseER statusResidual diseaseER-/HER2HER2 cancersBetter prognosisBreast cancerHER2-positive breast cancerImmune gene signaturesSystemic adjuvant therapyPositive breast cancerEstrogen receptor statusHigher chemotherapy sensitivityDistinct molecular subtypesNeoadjuvant taxaneAdjuvant therapyImmune signaturesComplete responseReceptor statusHER2 patientsPoor prognosisMolecular subtypesChemotherapy sensitivityPredictive valueHER2DNA repair metagene signature as a prognostic and predictive factor in molecular breast cancer subtypes.
Santarpia L, Iwamoto T, Di Leo A, Hayashi N, Stampfer M, Guarducci C, Symmans W, Hortobagyi G, Pusztai L, Giampaolo B. DNA repair metagene signature as a prognostic and predictive factor in molecular breast cancer subtypes. Journal Of Clinical Oncology 2012, 30: 1012-1012. DOI: 10.1200/jco.2012.30.15_suppl.1012.Peer-Reviewed Original ResearchPathological complete responseHigher pathological complete responseBreast cancer molecular subtypesTaxane-based regimensTaxane-containing regimensCisplatin-containing regimensMolecular breast cancer subtypesTaxane-based chemotherapyPotential predictive markerBreast cancer subtypesCancer molecular subtypesBC cell linesFalse discovery correctionDistant relapseComplete responseBetter prognosisPoor prognosisPredictive factorsPrognostic valueBC subtypesER-/HER2Predictive markerN patientsPrognostic markerMolecular subtypesA dendritic metagene that predicts prognosis and endocrine resistance in breast cancer.
Giampaolo B, Pusztai L, Qi Y, Iwamoto T, Kelly C, Zambetti M, Symmans W, Gianni L. A dendritic metagene that predicts prognosis and endocrine resistance in breast cancer. Journal Of Clinical Oncology 2012, 30: 545-545. DOI: 10.1200/jco.2012.30.15_suppl.545.Peer-Reviewed Original ResearchHazard ratioEndocrine resistanceBreast cancerNeoadjuvant endocrine therapyProliferative breast cancersAdjuvant tamoxifenEndocrine therapyDistant relapseFree survivalUntreated patientsBetter prognosisDendritic cellsEarly relapseOncotype DXPoor prognosisClinical variablesPoor responseUntreated tumorsLower riskMetagene signaturePredictive valueMultivariate analysisTumorsRelapsePrognosis
2011
Homogeneous Datasets of Triple Negative Breast Cancers Enable the Identification of Novel Prognostic and Predictive Signatures
Karn T, Pusztai L, Holtrich U, Iwamoto T, Shiang CY, Schmidt M, Müller V, Solbach C, Gaetje R, Hanker L, Ahr A, Liedtke C, Ruckhäberle E, Kaufmann M, Rody A. Homogeneous Datasets of Triple Negative Breast Cancers Enable the Identification of Novel Prognostic and Predictive Signatures. PLOS ONE 2011, 6: e28403. PMID: 22220191, PMCID: PMC3248403, DOI: 10.1371/journal.pone.0028403.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsCohort StudiesDatabases, GeneticFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansKaplan-Meier EstimateNeoadjuvant TherapyPredictive Value of TestsPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneReproducibility of ResultsConceptsPrognostic signatureValidation cohortBreast cancerPredictive valueTriple-negative breast cancerEvent-free survivalTriple-negative cancersHigh-risk groupIndependent validation cohortNegative breast cancerModest predictive valuePrognostic gene signaturePrognostic gene setsTNBC cohortNeoadjuvant chemotherapyPrognostic predictorPoor prognosisRisk groupsMultivariate analysisPredictive signatureNovel prognosticGene signatureSmall sample sizeCohortCancerPD03-02: Prognostic and Predictive Predictors for Triple Negative Breast Cancer.
Karn T, Pusztai L, Ruckhäberle E, Liedtke C, Schmidt M, Müller V, Gätje R, Hanker L, Ahr A, Holtrich U, Rody A, Kaufmann M. PD03-02: Prognostic and Predictive Predictors for Triple Negative Breast Cancer. Cancer Research 2011, 71: pd03-02-pd03-02. DOI: 10.1158/0008-5472.sabcs11-pd03-02.Peer-Reviewed Original ResearchTriple-negative breast cancerNegative breast cancerPrognostic signatureBreast cancerResponse of TNBCER-positive cancersPrognostic gene signatureMolecular phenotypesTNBC cohortNeoadjuvant chemotherapyHazard ratioBetter prognosisPrognostic predictorTherapeutic optionsPoor prognosisIndependent cohortPredictive valuePrognostic gene expression profilesMultivariate analysisGene signatureCancer ResCohortCancerPrognosisROC analysisMelanoma antigen family A identified by the bimodality index defines a subset of triple negative breast cancers as candidates for immune response augmentation
Karn T, Pusztai L, Ruckhäberle E, Liedtke C, Müller V, Schmidt M, Metzler D, Wang J, Coombes KR, Gätje R, Hanker L, Solbach C, Ahr A, Holtrich U, Rody A, Kaufmann M. Melanoma antigen family A identified by the bimodality index defines a subset of triple negative breast cancers as candidates for immune response augmentation. European Journal Of Cancer 2011, 48: 12-23. PMID: 21741824, DOI: 10.1016/j.ejca.2011.06.025.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAlgorithmsBreast NeoplasmsCancer VaccinesCarcinomaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHealth Status IndicatorsHumansImmunotherapyMelanoma-Specific AntigensMicroarray AnalysisMiddle AgedReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsTriple-negative breast cancerCancer/testis antigensNegative breast cancerBreast cancerTestis antigensMelanoma antigen family AHuman epidermal growth factor receptor 2 (HER2) receptorsImmune response augmentationImmune-stimulatory drugsMAGE-A antigensHigh expressionLymph node statusDistinct disease subsetsLess prognostic valueHigher MAGELow MAGEWorse survivalNode statusPoor prognosisPrognostic valueDisease subsetsImmune infiltrationPredictive markerImmune metagenesImmune responseDistinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers
Coutant C, Rouzier R, Qi Y, Lehmann-Che J, Bianchini G, Iwamoto T, Hortobagyi GN, Symmans WF, Uzan S, Andre F, de Thé H, Pusztai L. Distinct p53 Gene Signatures Are Needed to Predict Prognosis and Response to Chemotherapy in ER-Positive and ER-Negative Breast Cancers. Clinical Cancer Research 2011, 17: 2591-2601. PMID: 21248301, DOI: 10.1158/1078-0432.ccr-10-1045.Peer-Reviewed Original ResearchConceptsER- cancersPredictive valueBreast cancerP53 signatureWorse distant metastasis-free survivalDistant metastasis-free survivalER-negative breast cancerAdjuvant tamoxifen therapyDifferent molecular subsetsMetastasis-free survivalDifferent prognostic valueNegative breast cancerHigher chemotherapy sensitivityTamoxifen therapyFree survivalBetter prognosisER-positivePoor prognosisPrognostic valuePrognostic markerMolecular subsetsChemotherapy sensitivityMutation statusP53 mutationsMultivariate analysis
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 I