2024
Circulating tumor DNA fraction predicts residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer
Shan N, Gould B, Wang X, Bonora G, Blenman K, Foldi J, Campos G, Walsh M, Du P, Pusztai L. Circulating tumor DNA fraction predicts residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer. The Journal Of Liquid Biopsy 2024, 6: 100168. DOI: 10.1016/j.jlb.2024.100168.Peer-Reviewed Original ResearchTriple negative breast cancerResidual cancer burdenCirculating tumor DNANegative breast cancerPathological responsePost-NACBreast cancerPlasma circulating tumor DNATriple negative breast cancer patientsResidual cancer burden scoreCirculating tumour DNA fractionPost-neoadjuvant chemotherapyPre-NAC samplesWeekly nab-paclitaxelTumor DNA methylation profilesTumor DNA fractionHot spot mutationsYouden's J statisticNab-paclitaxelPre-NACTumor variantsTumor DNATumor fractionClinical trialsDNA methylation profilesCorrelation of hormone receptor positive HER2-negative/MammaPrint high-2 breast cancer with triple negative breast cancer: Results from gene expression data from the ISPY2 trial.
Rios-Hoyo A, Xiong K, Marczyk M, García-Millán R, Wolf D, Huppert L, Nanda R, Yau C, Hirst G, van 't Veer L, Esserman L, Pusztai L. Correlation of hormone receptor positive HER2-negative/MammaPrint high-2 breast cancer with triple negative breast cancer: Results from gene expression data from the ISPY2 trial. Journal Of Clinical Oncology 2024, 42: 573-573. DOI: 10.1200/jco.2024.42.16_suppl.573.Peer-Reviewed Original ResearchGene expression dataGene expression analysisExpression dataExpressed genesExpression analysisTriple-negativeDistance analysisPathway analysisDifferential gene expression analysisCell cycle pathwayGene set enrichment analysisBreast cancerIngenuity Pathway AnalysisRate of pathological complete responseHigh-risk stage IIGlucocorticoid receptor signalingTriple negative breast cancerCycle pathwayPathological complete responseDNA repairEnrichment analysisOptimal treatment strategyNegative breast cancerI-SPY2 trialGenesPopulation attributable fraction of reproductive factors in triple negative breast cancer by race.
Jaber Chehayeb R, Odzer N, Albany R, Phipps A, Meisner A, Pusztai L. Population attributable fraction of reproductive factors in triple negative breast cancer by race. Journal Of Clinical Oncology 2024, 42: 10522-10522. DOI: 10.1200/jco.2024.42.16_suppl.10522.Peer-Reviewed Original ResearchPopulation-attributable fractionAA womenIncidence of triple negative breast cancerPooled odds ratioOdds ratioWhite womenTriple negative breast cancerNon-Hispanic White (WhiteRelative riskRace-specific odds ratiosBreast cancerIncidence rates of triple negative breast cancerEstimates of relative riskContribution of multiple risk factorsTNBC incidenceRelevant case-control studiesPopulation attributable fractionRisk factorsYounger ageNegative breast cancerCase-control studyMultiple risk factorsBreastfeeding uptakeAttributable fractionLevin's formulaNavigating practical challenges in immunotherapy for metastatic triple negative breast cancer
Licata L, Dieci M, De Angelis C, Marchiò C, Miglietta F, Cortesi L, Fabi A, Schmid P, Cortes J, Pusztai L, Bianchini G, Curigliano G. Navigating practical challenges in immunotherapy for metastatic triple negative breast cancer. Cancer Treatment Reviews 2024, 128: 102762. PMID: 38776613, DOI: 10.1016/j.ctrv.2024.102762.Peer-Reviewed Original ResearchTriple-negative breast cancerBreast cancerMetastatic triple negative breast cancerManagement of breast cancer patientsTriple negative breast cancerApproval of immunotherapyImmune checkpoint inhibitorsNegative breast cancerBreast cancer patientsEveryday clinical practiceCheckpoint inhibitorsTumor typesCancer patientsClinical trialsCancer therapyImmunotherapyCancerClinical practicePositive resultsCliniciansTumorTherapyPatientsTrialsInhibitors
2023
Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer
Kahn A, Golestani R, Harigopal M, Pusztai L. Intratumor spatial heterogeneity in programmed death-ligand 1 (PD-L1) protein expression in early-stage breast cancer. Breast Cancer Research And Treatment 2023, 201: 289-298. PMID: 37378695, DOI: 10.1007/s10549-023-06977-1.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPD-L1 expressionBreast cancerPD-L1Metastatic triple-negative breast cancerPD-L1 positive casesEarly-stage breast cancerPD-L1 protein expressionImmune checkpoint inhibitorsPD-L1 positivityPD-L1 statusProtein expressionWhole study populationPrimary breast tumorsNegative breast cancerConcordant negative resultsCheckpoint inhibitorsMultiple biopsiesPositive cancersCohen's kappa coefficientStudy populationE1L3N antibodyDiscordance rateBreast tumorsPositive cases
2022
Tumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer
Marczyk M, Qing T, O’Meara T, Yagahoobi V, Pelekanou V, Bai Y, Reisenbichler E, Cole KS, Li X, Gunasekharan V, Ibrahim E, Fanucci K, Wei W, Rimm DL, Pusztai L, Blenman KRM. Tumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer. Npj Breast Cancer 2022, 8: 88. PMID: 35869114, PMCID: PMC9307813, DOI: 10.1038/s41523-022-00449-3.Peer-Reviewed Original ResearchTumor immune microenvironmentImmune microenvironmentTriple-negative breast cancer tissuesTriple-negative breast cancerAfrican AmericansImmune checkpoint inhibitorsTumor mutation burdenNegative breast cancerBreast cancer tissuesImmune-related pathwaysStromal TILsCheckpoint inhibitorsImmune exclusionClinical outcomesPD-L1Self-identified African AmericansCancer patientsImmune infiltrationBreast cancerMutation burdenCancer tissuesPredictive signatureMRNA expressionTherapeutic agentsPatientsThe mutational profile of ER-, PR+, HER2- metastatic breast cancer.
Fischbach N, Huang R, Lustberg M, Pelletier M, Pusztai L, Sivakumar S, Sokol E, Ross J, Levy M. The mutational profile of ER-, PR+, HER2- metastatic breast cancer. Journal Of Clinical Oncology 2022, 40: 1025-1025. DOI: 10.1200/jco.2022.40.16_suppl.1025.Peer-Reviewed Original ResearchTriple-negative breast cancerComprehensive genomic profilingMetastatic breast cancerBreast cancerClinical trialsPathology reportsMutational profileHER2- metastatic breast cancerConsecutive breast cancersAnti-estrogen therapyNegative breast cancerPD-L1 IHCPotential therapeutic implicationsHigh rateEndocrine therapyEstrogen therapyPatient ageFoundation MedicineKRAS alterationsRare subtypeHER2 expressionClinical behaviorReceptor phenotypeBreast carcinomaTreatment strategiesBiomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update
Andre F, Ismaila N, Allison KH, Barlow WE, Collyar DE, Damodaran S, Henry NL, Jhaveri K, Kalinsky K, Kuderer NM, Litvak A, Mayer EL, Pusztai L, Raab R, Wolff AC, Stearns V. Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update. Journal Of Clinical Oncology 2022, 40: 1816-1837. PMID: 35439025, DOI: 10.1200/jco.22.00069.Peer-Reviewed Original ResearchConceptsBreast Cancer IndexEarly-stage breast cancerHER2- breast cancerAdjuvant endocrinePositive nodesBreast cancerEndocrine therapyPostmenopausal patientsPremenopausal patientsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Early-stage estrogen receptorTriple-negative breast cancerAdjuvant therapy decisionsASCO Guideline UpdateExtended endocrine therapyProspective-retrospective studyEvidence of recurrenceGrowth factor receptor 2Recurrence-free survivalGenomic testsNegative breast cancerEvidence-based recommendationsFactor receptor 2Outcomes of interestPredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycle
2021
Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study
Yaghoobi V, Moutafi M, Aung TN, Pelekanou V, Yaghoubi S, Blenman K, Ibrahim E, Vathiotis IA, Shafi S, Sharma A, O’Meara T, Fernandez AI, Pusztai L, Rimm DL. Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case–control study. Breast Cancer Research 2021, 23: 113. PMID: 34906209, PMCID: PMC8670126, DOI: 10.1186/s13058-021-01493-w.Peer-Reviewed Original ResearchConceptsNegative breast cancerT cellsTumor microenvironmentAA patientsImmune cellsAA tumorsBreast cancerPurposeTriple-negative breast cancerAfrican AmericansTriple-negative breast cancerCase-control studySignificant differencesActivated T cellsImmunologic biomarkersPD-L1Lymphocytic infiltrationLymphoid infiltrationImmune microenvironmentControl cohortTNBC tumorsMyeloid markersQuantitative immunofluorescenceMean expression levelPatientsTNBCCharacterization of the tumor immune microenvironment of triple-negative breast cancer (TNBC) patients who self-identify as African American (AA) or non-African American (NonAA).
Blenman K, Marczyk M, Qing T, O'Meara T, Yaghoobi V, Pelekanou V, Bai Y, Reisenbichler E, Li X, Gunasekharan V, Ibrahim E, Rimm D, Pusztai L, Cole K. Characterization of the tumor immune microenvironment of triple-negative breast cancer (TNBC) patients who self-identify as African American (AA) or non-African American (NonAA). Journal Of Clinical Oncology 2021, 39: 564-564. DOI: 10.1200/jco.2021.39.15_suppl.564.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor immune microenvironmentAA patientsImmune microenvironmentWhole-exome sequencingAfrican AmericansTriple-negative breast cancer patientsYale Cancer CenterImmune checkpoint inhibitorsPD-L1 positivityPD-L1 expressionYear of diagnosisBreast cancer patientsCytokines/chemokinesImmune cell compositionTumor mutational burdenGermline whole-exome sequencingAge of diagnosisNegative breast cancerCorresponding clinical dataAllograft rejection pathwayNon-African AmericansSomatic mutationsFatty acid metabolismCheckpoint inhibitorsPredicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy
Du L, Yau C, Brown-Swigart L, Gould R, Krings G, Hirst G, Bedrosian I, Layman R, Carter J, Klein M, Venters S, Shad S, van der Noordaa M, Chien A, Haddad T, Isaacs C, Pusztai L, Albain K, Nanda R, Tripathy D, Liu M, Boughey J, Schwab R, Hylton N, DeMichele A, Perlmutter J, Yee D, Berry D, Veer L, Valero V, Esserman L, Symmans W. Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy. Annals Of Oncology 2021, 32: 642-651. PMID: 33617937, DOI: 10.1016/j.annonc.2021.02.011.Peer-Reviewed Original ResearchConceptsResidual cancer burdenI-SPY2 trialIndependent prognostic informationPrognostic informationBreast cancerPrognostic signaturePre-treatment tumor biopsiesHER2-negative breast cancerStage IIDistant relapse-free survivalMultivariate Cox regression modelHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Chemo-endocrine therapyEndocrine-based treatmentAdjuvant endocrine therapyGrowth factor receptor 2Primary outcome measureRelapse-free survivalSimilar prognostic informationCox regression modelMolecular prognostic signaturesNegative breast cancerFactor receptor 2MDACC cohort
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 ResearchConceptsPD-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 coefficientImmunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers
O’Meara T, Marczyk M, Qing T, Yaghoobi V, Blenman K, Cole K, Pelekanou V, Rimm DL, Pusztai L. Immunological Differences Between Immune-Rich Estrogen Receptor–Positive and Immune-Rich Triple-Negative Breast Cancers. JCO Precision Oncology 2020, 4: po.19.00350. PMID: 32923897, PMCID: PMC7446500, DOI: 10.1200/po.19.00350.Peer-Reviewed Original ResearchER-positive breast cancerTriple-negative BCM2-like macrophagesTumor-infiltrating lymphocytesBreast cancerImmune-related genesEstrogen receptor-positive breast cancerImmuno-oncology therapeutic targetsRegulatory T cell markersReceptor-positive breast cancerTriple-negative breast cancerImmune activation markersT-cell markersImmune cell markersM1-like macrophagesDifferent immunotherapy strategiesBreast Cancer International ConsortiumNegative breast cancerImmuno-oncology trialsTGF-β pathwayAntitumor immunityCancer Genome AtlasImmunotherapy strategiesActivation markersImmune microenvironmentProspective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer
Reisenbichler ES, Han G, Bellizzi A, Bossuyt V, Brock J, Cole K, Fadare O, Hameed O, Hanley K, Harrison BT, Kuba MG, Ly A, Miller D, Podoll M, Roden AC, Singh K, Sanders MA, Wei S, Wen H, Pelekanou V, Yaghoobi V, Ahmed F, Pusztai L, Rimm DL. Prospective multi-institutional evaluation of pathologist assessment of PD-L1 assays for patient selection in triple negative breast cancer. Modern Pathology 2020, 33: 1746-1752. PMID: 32300181, PMCID: PMC8366569, DOI: 10.1038/s41379-020-0544-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNegative breast cancerOverall percent agreementPD-L1Intraclass correlation coefficientBreast cancerAdvanced triple-negative breast cancerPD-L1 positive casesImmune cell stainingMultiple pathologistsPD-L1 scoringMulti-institutional evaluationLung cancer studiesAtezolizumab therapySP142 assaySP263 assaysPatient selectionSP263SP142US FoodDrug AdministrationPathologist's assessmentPositive casesReal-world settingPercent agreement
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 developmentChanging frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers
Pusztai L, Foldi J, Dhawan A, DiGiovanna MP, Mamounas EP. Changing frameworks in treatment sequencing of triple-negative and HER2-positive, early-stage breast cancers. The Lancet Oncology 2019, 20: e390-e396. PMID: 31267973, DOI: 10.1016/s1470-2045(19)30158-5.Commentaries, Editorials and LettersConceptsEarly-stage breast cancerHER2-positive breast cancerBreast cancerClinical trialsNeoadjuvant chemotherapyEstrogen receptor-negative breast cancerImproved disease-free survivalReceptor-negative breast cancerParticular chemotherapy regimenResidual invasive cancerNeoadjuvant systemic therapyDisease-free survivalImportant clinical trialsAdo-trastuzumab emtansineNegative breast cancerAdjuvant settingKATHERINE trialOperable diseasePostoperative capecitabineChemotherapy regimenMetastatic diseaseSystemic therapyResidual diseaseInvasive cancerTreatment sequencing
2018
Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC).
Pusztai L, Hofstatter E, Chung G, Horowitz N, Lannin D, Killelea B, Chagpar A, DiGiovanna M, Frederick C, Burello T, Harigopal M. Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC). Journal Of Clinical Oncology 2018, 36: 586-586. DOI: 10.1200/jco.2018.36.15_suppl.586.Peer-Reviewed Original Research
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 2Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races.
Szekely B, Safonov A, Karn T, Bhagwagar S, Killelea B, Silber A, Hatzis C, Pusztai L. Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races. Journal Of Clinical Oncology 2017, 35: e13028-e13028. DOI: 10.1200/jco.2017.35.15_suppl.e13028.Peer-Reviewed Original ResearchTriple-negative breast cancerNon-AA patientsImmune microenvironmentAfrican American womenImmune signaturesNeoantigen loadImmune metagenesLower pathologic complete response (pCR) ratesPathologic complete response rateComplete response rateNegative breast cancerAmerican womenMann-Whitney U testSignificant differencesClonal heterogeneityTCGA data setsDeletion loadNeoadjuvant therapyLymphocyte countTIL countAA patientsOverall mutational loadHistologic tumorsBreast cancerTreatment response