2023
LBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC)
Loi S, Curigliano G, Salgado R, Diaz R, Delaloge S, Rojas C, Kok M, Manich C, Harbeck N, Mittendorf E, Yardley D, Pusztai L, Zaizar A, Ungureanu A, Ades F, Chandra R, Nathani R, Pacius M, Wu J, McArthur H. LBA20 A randomized, double-blind trial of nivolumab (NIVO) vs placebo (PBO) with neoadjuvant chemotherapy (NACT) followed by adjuvant endocrine therapy (ET) ± NIVO in patients (pts) with high-risk, ER+ HER2− primary breast cancer (BC). Annals Of Oncology 2023, 34: s1259-s1260. DOI: 10.1016/j.annonc.2023.10.010.Peer-Reviewed Original ResearchHRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).
Jeon J, Chen K, Madison R, Schrock A, Sokol E, Levy M, Oxnard G, Huang R, Pusztai L. HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC). Journal Of Clinical Oncology 2023, 41: 539-539. DOI: 10.1200/jco.2023.41.16_suppl.539.Peer-Reviewed Original ResearchEarly-stage breast cancerPrimary breast cancerEarly breast cancerBreast cancerStage IHR-/HER2HRR deficiencyPALB2 mutationsEarly-stage primary breast cancerPARP inhibitorsStage IV diseaseHormone receptor statusMonths of diagnosisPositive breast cancerHomologous recombination repairComprehensive genomic profilingHRD signaturesClinical trial dataHigh rateSEER studySomatic BRCAAdjuvant therapyAdvanced diseaseReceptor statusBC subtypes
2021
Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples
Fu C, Marczyk M, Samuels M, Trevarton AJ, Qu J, Lau R, Du L, Pappas T, Sinn BV, Gould RE, Pusztai L, Hatzis C, Symmans WF. Targeted RNAseq assay incorporating unique molecular identifiers for improved quantification of gene expression signatures and transcribed mutation fraction in fixed tumor samples. BMC Cancer 2021, 21: 114. PMID: 33541297, PMCID: PMC7860187, DOI: 10.1186/s12885-021-07814-8.Peer-Reviewed Original ResearchConceptsPolymerase chain reactionParaffin-embedded tumor tissue samplesConcordance correlation coefficientFresh frozenFFPE samplesPrimary breast cancerMulti-gene signatureTumor tissue samplesActivating point mutationMutant allele fractionReverse transcriptionKey breast cancer genesGene expression signaturesBreast cancer genesPIK3CA mutationsBackgroundOur objectiveBreast cancerWhole transcriptome RNAseqTumor samplesLin's concordance correlation coefficientHormone receptorsFF samplesTissue samplesExpression signaturesChain reaction
2020
A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL.
Loi S, McArthur H, Harbeck N, Pusztai L, Delaloge S, Letrent K, Chen T, Li B, Tatsuoka K, Zardavas D, Curigliano G. A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL. Journal Of Clinical Oncology 2020, 38: tps604-tps604. DOI: 10.1200/jco.2020.38.15_suppl.tps604.Peer-Reviewed Original ResearchAdjuvant endocrine therapyPathologic complete responsePrimary breast cancerEndocrine therapyNeoadjuvant chemotherapyBreast cancerNeoadjuvant phaseER expressionGlobal phase 3 studyDeath ligand 1 (PD-L1) expressionLong-term clinical outcomesAdequate organ functionDeath-1 (PD-1) inhibitionLow ER expressionAxillary nodal statusDisease-free survivalEvent-free survivalLigand 1 expressionPhase III trialsResidual cancer burdenPhase 3 studyOverall response rateRisk of relapseValid surrogate endpointQuality of life134TiP A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2− primary breast cancer: CheckMate 7FL
Curigliano G, McArthur H, Harbeck N, Pusztai L, Delaloge S, Letrent K, Chen T, Li B, Tatsuoka K, Zardavas D, Loi S. 134TiP A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2− primary breast cancer: CheckMate 7FL. Annals Of Oncology 2020, 31: s60-s61. DOI: 10.1016/j.annonc.2020.03.236.Peer-Reviewed Original Research
2019
Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
Li X, Warren S, Pelekanou V, Wali V, Cesano A, Liu M, Danaher P, Elliott N, Nahleh ZA, Hayes DF, Hortobagyi GN, Barlow WE, Hatzis C, Pusztai L. Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial. Journal For ImmunoTherapy Of Cancer 2019, 7: 88. PMID: 30967156, PMCID: PMC6457012, DOI: 10.1186/s40425-019-0563-7.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual diseaseTIL countGene expression levelsHigh expressionCellular stressNeoadjuvant chemotherapyImmune genesImmune-related genesStromal genesImmune functionImmune microenvironment changesMost immune functionsGenesCell typesPD-L1 protein expressionStem cellsHigher TIL countsPD-L1 expressionExpression levelsPrimary breast cancerT-cell markersImmune cell typesProtein expressionStromal function
2017
Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer
Fujii T, Kogawa T, Dong W, Sahin AA, Moulder S, Litton JK, Tripathy D, Iwamoto T, Hunt KK, Pusztai L, Lim B, Shen Y, Ueno NT. Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Annals Of Oncology 2017, 28: 2420-2428. PMID: 28961844, PMCID: PMC5834134, DOI: 10.1093/annonc/mdx397.Peer-Reviewed Original ResearchConceptsHER2-negative primary breast cancerAdjuvant hormonal therapyPrimary breast cancerTriple-negative breast cancerEstrogen receptor positivityHormonal therapyBreast cancerER expressionNeoadjuvant chemotherapyOverall survivalReceptor positivityPathological complete response rateHER2-negative breast cancerStage IIHuman epidermal growth factor 2Better long-term outcomesEpidermal growth factor 2Complete response rateProgesterone receptor expressionLong-term outcomesNegative breast cancerTerms of pCRLogistic regression modelsDefinitive surgeryGrowth factor 2
2016
A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer
Hadad SM, Jordan LB, Roy PG, Purdie CA, Iwamoto T, Pusztai L, Moulder-Thompson SL, Thompson AM. A prospective comparison of ER, PR, Ki67 and gene expression in paired sequential core biopsies of primary, untreated breast cancer. BMC Cancer 2016, 16: 745. PMID: 27658825, PMCID: PMC5034430, DOI: 10.1186/s12885-016-2788-x.Peer-Reviewed Original ResearchIngenuity Pathway AnalysisBreast cancerCore biopsyDrug therapyOperable breast cancerSequential core biopsiesUntreated breast cancerHormone receptor statusPrimary breast cancerPathway analysisPR immunohistochemistryUntreated patientsReceptor statusPrimary cancerNon-treatment controlBiomarker statusProspective comparisonBiomarker changesDrug interventionKi67 scoreBiopsyBiomarker effectsDrug efficacyKi67MRNA expression
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
Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer
Jeselsohn R, Yelensky R, Buchwalter G, Frampton G, Meric-Bernstam F, Gonzalez-Angulo AM, Ferrer-Lozano J, Perez-Fidalgo JA, Cristofanilli M, Gómez H, Arteaga CL, Giltnane J, Balko JM, Cronin MT, Jarosz M, Sun J, Hawryluk M, Lipson D, Otto G, Ross JS, Dvir A, Soussan-Gutman L, Wolf I, Rubinek T, Gilmore L, Schnitt S, Come SE, Pusztai L, Stephens P, Brown M, Miller VA. Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer. Clinical Cancer Research 2014, 20: 1757-1767. PMID: 24398047, PMCID: PMC3998833, DOI: 10.1158/1078-0432.ccr-13-2332.Peer-Reviewed Original ResearchConceptsEstrogen receptor α mutationBreast cancerAdvanced estrogen receptor-positive breast cancerEstrogen receptor-positive breast cancerReceptor-positive breast cancerHormone-dependent breast cancerPrimary breast cancerSubgroup of patientsER-negative tumorsLine of treatmentCodon 537ER- diseaseEndocrine treatmentTreatment-naïveESR1 mutationsMetastatic diseaseCell line modelsEndocrine resistanceMetastatic tumorsReceptor constitutive activityEstrogen receptorMetastatic samplesTumor specimensCancer-related genesNatural history
2013
Genomic alterations in matching primary tumors and metastasis in breast cancer.
Jiang T, Szekely B, Szasz A, Kluger Y, Kulka J, Pusztai L. Genomic alterations in matching primary tumors and metastasis in breast cancer. Journal Of Clinical Oncology 2013, 31: 1549-1549. DOI: 10.1200/jco.2013.31.15_suppl.1549.Peer-Reviewed Original ResearchPrimary tumorPrimary cancerBreast cancerMetastatic lesionsDisease historyExtensive prior therapyPrimary breast cancerLonger disease historyWhole-exome sequencingDifferent tumor sitesFunctional impactPrior therapyNucleotide variantsMetastasisPatientsTumor siteTumorsCancerNormal tissuesCancer samplesExome sequencingGenomic alterationsLesionsMore mutationsExon Kit
2012
High stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients
Holder AM, Gonzalez-Angulo AM, Chen H, Akcakanat A, Do KA, Fraser Symmans W, Pusztai L, Hortobagyi GN, Mills GB, Meric-Bernstam F. High stearoyl-CoA desaturase 1 expression is associated with shorter survival in breast cancer patients. Breast Cancer Research And Treatment 2012, 137: 319-327. PMID: 23208590, PMCID: PMC3556743, DOI: 10.1007/s10549-012-2354-4.Peer-Reviewed Original ResearchConceptsRelapse-free survivalShorter relapse-free survivalBreast cancerOverall survivalPatient ageMultivariable analysisClinical stageSCD1 levelsSCD1 expressionTumor subtypesStearoyl-CoA desaturase 1 expressionTriple-negative breast cancerMartingale residual plotsPrimary breast cancerSurvival of patientsBreast cancer patientsClinical pathologic characteristicsTumor clinical stageDesaturase 1 expressionBreast cancer subtypesBreast cancer cell linesExpression levelsRole of SCD1Fine needle aspiratesOverexpression of SCD112O_PR Independent Blinded Validation of the Genomic Index of Sensitivity to Endocrine Therapy (Set)
Karn T, Hatzis C, Symmans W, Pusztai L, Ruckhäberle E, Schmidt M, Müller V, Holtrich U, Rody A, Kaufmann M. 12O_PR Independent Blinded Validation of the Genomic Index of Sensitivity to Endocrine Therapy (Set). Annals Of Oncology 2012, 23: ii18. DOI: 10.1016/s0923-7534(19)65684-x.Peer-Reviewed Original ResearchEndocrine therapyPositive patientsPrognostic valueTumor sizeER-positive primary breast cancerPositive primary breast cancerAdjuvant endocrine therapyNegative PgR statusNode-negative cohortPure prognostic valueNode-negative patientsStepwise Cox regressionER-positive patientsPrimary breast cancerBest independent predictorPgR statusAdjuvant treatmentRetrospective cohortIndependent predictorsLymph nodesNegative cohortSurvival benefitCox regressionClinical associationsHER2 statusEstrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry
Iwamoto T, Booser D, Valero V, Murray JL, Koenig K, Esteva FJ, Ueno NT, Zhang J, Shi W, Qi Y, Matsuoka J, Yang EJ, Hortobagyi GN, Hatzis C, Symmans WF, Pusztai L. Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry. Journal Of Clinical Oncology 2012, 30: 729-734. PMID: 22291085, DOI: 10.1200/jco.2011.36.2574.Peer-Reviewed Original ResearchConceptsER-positive patientsIHC-positive patientsER-positive cancersESR1 mRNA expressionGene signature scoreER statusBreast cancerSignature scoreEstrogen receptor-positive cancersMRNA expressionAdjuvant endocrine therapyEndocrine-sensitive tumorsER-negative cohortER-positive cohortER-negative groupER-positive tumorsOverall survival ratePrimary breast cancerER-negative cancersReceptor-positive cancersSafe clinical approachEstrogen receptor mRNAEndocrine therapyER-positiveAffymetrix U133A gene chipsLapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, Team O. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2012, 379: 633-640. PMID: 22257673, PMCID: PMC5705192, DOI: 10.1016/s0140-6736(11)61847-3.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDiarrheaDrug Administration ScheduleFemaleHumansInfusions, IntravenousLapatinibLiverMiddle AgedNeoadjuvant TherapyPaclitaxelQuinazolinesReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsPathological complete responseBreast cancerHER2-positive early breast cancerHER2-positive primary breast cancerAnti-HER2 monoclonal antibody trastuzumabHER2-positive breast cancerHER2-overexpressing breast cancerTyrosine kinase inhibitor lapatinibGrade 3 diarrheaLiver enzyme alterationsAnti-HER2 agentsAnti-HER2 therapyPhase 3 studyPhase 3 trialEarly breast cancerPrimary breast cancerSingle-agent therapySynergistic antitumour activityMajor cardiac dysfunctionKinase inhibitor lapatinibMonoclonal antibody trastuzumabAdjuvant chemotherapyNeoadjuvant phaseNeoadjuvant settingOral lapatinib
2011
Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer
Kaufmann M, von Minckwitz G, Mamounas EP, Cameron D, Carey LA, Cristofanilli M, Denkert C, Eiermann W, Gnant M, Harris JR, Karn T, Liedtke C, Mauri D, Rouzier R, Ruckhaeberle E, Semiglazov V, Symmans WF, Tutt A, Pusztai L. Recommendations from an International Consensus Conference on the Current Status and Future of Neoadjuvant Systemic Therapy in Primary Breast Cancer. Annals Of Surgical Oncology 2011, 19: 1508-1516. PMID: 22193884, DOI: 10.1245/s10434-011-2108-2.Peer-Reviewed Original ResearchConceptsNeoadjuvant systemic therapyPrimary breast cancerBreast cancerSystemic therapyBreast-conserving surgery rateLarge adjuvant trialsPathologic complete responseInflammatory breast cancerNew therapeutic regimensIntermediate end pointsInternational Consensus ConferenceClinical research groupAdjuvant trialsNew regimensPathologic responseComplete responseSurgery ratesTherapeutic regimensConsensus conferenceEnd pointTherapyCancerTrialsRegimensPanel of representativesP1-07-09: Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1%-10% ER-Positive by Immunohistochemistry.
Iwamoto T, Booser D, Valero V, Murray J, Koenig K, Esteva F, Ueno N, Zhang J, Shi W, Qi Y, Matsuoka J, Hortobagyi G, Hatzis C, Symmans W, Pusztai L. P1-07-09: Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1%-10% ER-Positive by Immunohistochemistry. Cancer Research 2011, 71: p1-07-09-p1-07-09. DOI: 10.1158/0008-5472.sabcs11-p1-07-09.Peer-Reviewed Original ResearchER-positive casesER-positive cancersESR1 mRNA expressionGene signature scoreIHC-positive casesLuminal ABreast cancerSignature scoreMRNA expressionER-negative cancersPrimary breast cancerESR1 mRNA levelsEstrogen receptor mRNAER expressionER statusER-positivePositive cancersAffymetrix U133A gene chipsLuminal BSensitive tumorsEstrogen receptorB. ConclusionReceptor mRNAESR1 expressionPositive casesFunctional proteomics can define prognosis and predict pathologic complete response in patients with breast cancer
Gonzalez-Angulo AM, Hennessy BT, Meric-Bernstam F, Sahin A, Liu W, Ju Z, Carey MS, Myhre S, Speers C, Deng L, Broaddus R, Lluch A, Aparicio S, Brown P, Pusztai L, Symmans WF, Alsner J, Overgaard J, Borresen-Dale AL, Hortobagyi GN, Coombes KR, Mills GB. Functional proteomics can define prognosis and predict pathologic complete response in patients with breast cancer. Clinical Proteomics 2011, 8: 11. PMID: 21906370, PMCID: PMC3170272, DOI: 10.1186/1559-0275-8-11.Peer-Reviewed Original ResearchRecurrence-free survivalPathological complete responseBreast cancerComplete responseBiomarker panelDifferent recurrence-free survivalPathologic complete responseCohort of patientsPrimary breast cancerManagement of patientsBreast cancer subgroupsSurgical excision specimensProbability of recurrenceNeoadjuvant taxaneSystemic therapyPrognostic scorePrognostic groupsPrognosis scoreOrdinal logistic regressionCancer subgroupsExcision specimensPatientsFNA biopsySignificant associationPhase protein arrayEvidence 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
Estrogen 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 results