2024
Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer
Campbell M, Wolf D, Yau C, Brown-Swigart L, Wulfkuhle J, Gallagher I, Zhu Z, Bolen J, Vandenberg S, Hoyt C, Mori H, Borowsky A, Sit L, Perlmutter J, Asare S, Investigators I, Nanda R, Liu M, Yee D, DeMichele A, Hylton N, Pusztai L, Berry D, Hirst G, Petricoin E, Veer L, Esserman L. Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer. Cell Reports Medicine 2024, 5: 101799. PMID: 39510069, PMCID: PMC11604542, DOI: 10.1016/j.xcrm.2024.101799.Peer-Reviewed Original ResearchImmune checkpoint blockadeI-SPY 2 TRIALPathological complete responseTumor microenvironmentBreast cancerAssociated with pathologic complete responseBreast cancer receptor subtypesNeoadjuvant immune checkpoint blockadePD-L1<sup>+</sup> cellsSpatial distribution of immune cellsDistribution of immune cellsEarly-stage breast cancerImmune checkpoint inhibitorsBiomarkers of responseImmune cell populationsImmune cell densityAssociated with responseImmune cell signalingCheckpoint blockadeCheckpoint inhibitorsComplete responsePretreatment biopsiesReceptor subtypesT cellsImmune cellsPeripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer
Foldi J, Blenman K, Marczyk M, Gunasekharan V, Polanska A, Gee R, Davis M, Kahn A, Silber A, Pusztai L. Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 369-377. PMID: 39002068, DOI: 10.1007/s10549-024-07426-3.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerAssociated with pathological responsePathological complete responseNeoadjuvant chemotherapyCytokine levelsPathological responseAdverse eventsBreast cancerEarly-stage triple-negative breast cancerPatients treated with immune checkpoint inhibitorsB cell clonal expansionMeasured serum cytokine levelsImmune checkpoint inhibitorsGM-CSF levelsPeripheral blood cytokine levelsBlood cytokine levelsSerum cytokine levelsB cell receptorMagnetic bead panelBenjamini-Hochberg correctionSample of patientsImmunoSEQ platformCheckpoint inhibitorsComplete responseIncidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial.
Nanda R, Cohen R, Quandt Z, Basu A, Yau C, Chien A, Pusztai L, Han H, Stringer-Reasor E, Isaacs C, Hershman D, Shatsky R, Perlmutter J, Yee D, DeMichele A, van 't Veer L, Hylton N, Esserman L, Rugo H. Incidence and time to onset of immunotherapy-related adrenal insufficiency in the I-SPY2 trial. Journal Of Clinical Oncology 2024, 42: 584-584. DOI: 10.1200/jco.2024.42.16_suppl.584.Peer-Reviewed Original ResearchImmune-related adverse eventsImmune checkpoint inhibitorsEarly breast cancerIncidence of AIAdrenal insufficiencyI-SPY2Advanced diseaseBreast cancerRisk of immune-related adverse eventsHigh-risk early breast cancerImmune checkpoint inhibitor doseTriple-negative breast cancerAnti-LAG-3Approval of pembrolizumabEvaluate novel agentsICI-based therapyWeekly x 4Rate of adrenal insufficiencyPhase 2 trialI-SPY2 trialTime to onsetAge of ptsCheckpoint inhibitorsNeoadjuvant settingWeekly paclitaxelNavigating 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
The effectiveness of immune checkpoint inhibitors in the neoadjuvant and post-neoadjuvant breast cancer settings.
Pusztai L. The effectiveness of immune checkpoint inhibitors in the neoadjuvant and post-neoadjuvant breast cancer settings. Clinical Advances In Hematology And Oncology 2022, 20: 552-555. PMID: 36125946.Peer-Reviewed Original ResearchTumor 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 agentsPatients
2021
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).
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 inhibitorsDiverse immune response of DNA damage repair-deficient tumors
Qing T, Jun T, Lindblad KE, Lujambio A, Marczyk M, Pusztai L, Huang KL. Diverse immune response of DNA damage repair-deficient tumors. Cell Reports Medicine 2021, 2: 100276. PMID: 34095878, PMCID: PMC8149377, DOI: 10.1016/j.xcrm.2021.100276.Peer-Reviewed Original ResearchConceptsCancer typesDDR-deficient tumorsImmune checkpoint inhibitorsHigh neoantigen loadDifferent immune phenotypesDiverse immune responsesAdaptive immune markersRepair-deficient tumorsDDR deficiencyCheckpoint inhibitorsImmunotherapy outcomesDNA damage repair deficiencyImmune infiltratesImmune markersNeoantigen loadSurvival outcomesImmune phenotypeTumor neoantigensImmune responseAnimal modelsGenomic biomarkersGermline mutationsPathway mutationsTumorsRepair deficiency
2019
Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial.
Wulfkuhle J, Yau C, Wolf D, Gallagher R, Brown Swigart L, Hirst G, Campbell M, Nanda R, Liu M, Pusztai L, Esserman L, Berry D, van 't Veer L, Petricoin E. Quantitative MHC II protein expression levels in tumor epithelium to predict response to the PD1 inhibitor pembrolizumab in the I-SPY 2 Trial. Journal Of Clinical Oncology 2019, 37: 2631-2631. DOI: 10.1200/jco.2019.37.15_suppl.2631.Peer-Reviewed Original ResearchI-SPY 2 TRIALImmune checkpoint inhibitorsCheckpoint inhibitorsTumor epitheliumPD1 inhibitor pembrolizumabTumor antigen presentationHER2-negative subtypeMHC-II expressionTumor cell expressionPredictors of responseWilcoxon rank sum testPositive associationRank sum testProtein expression levelsImmune activationControl armAntigen presentationResponse predictorsHR subgroupsB cellsCell expressionPatientsSum testProtein expressionTumorsImmunotherapy and targeted therapy combinations in metastatic breast cancer
Esteva FJ, Hubbard-Lucey VM, Tang J, Pusztai L. Immunotherapy and targeted therapy combinations in metastatic breast cancer. The Lancet Oncology 2019, 20: e175-e186. PMID: 30842061, DOI: 10.1016/s1470-2045(19)30026-9.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerImmune checkpoint inhibitorsTumor-infiltrating lymphocytesDeath ligand 1Most breast cancersNew treatment modalitiesSingle-drug therapyCyclin-dependent kinase 4Development of combinationsCheckpoint inhibitorsEndocrine therapyDeath-1Immunotherapeutic approachesBiological therapyTherapy combinationsTreatment modalitiesLittle efficacyImmune evasionAngiogenesis inhibitorsTherapyImmunotherapyCancerPolymerase inhibitorsMonoclonal antibodies
2017
Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer
Safonov A, Jiang T, Bianchini G, Győrffy B, Karn T, Hatzis C, Pusztai L. Immune Gene Expression Is Associated with Genomic Aberrations in Breast Cancer. Cancer Research 2017, 77: 3317-3324. PMID: 28428277, DOI: 10.1158/0008-5472.can-16-3478.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesBreast cancer subtypesImmune infiltrationNeoantigen loadImmune surveillanceLower clonal heterogeneityCancer subtypesHigher immune gene expressionClonal heterogeneityImmune checkpoint inhibitorsMajor breast cancer subtypesFavorable prognostic factorTriple-negative cancersOverall mutation loadImmune gene expressionCheckpoint inhibitorsCancer Genome AtlasPrognostic factorsImmune metagenesBreast cancerCNV loadMutation loadGermline polymorphismsCancerCancer ResSafety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial.
Pusztai L, Silber A, Hofstatter E, Chung G, Horowitz N, Lannin D, Killelea B, Chagpar A, Szekely B, Frederick C, Rispoli L, DiGiovanna M. Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial. Journal Of Clinical Oncology 2017, 35: 572-572. DOI: 10.1200/jco.2017.35.15_suppl.572.Peer-Reviewed Original ResearchImmune related adverse eventsTriple-negative breast cancerWeekly nab-paclitaxelWeeks of therapyNeoadjuvant chemotherapyDose levelsNab-paclitaxelPhase I/II trialPathologic complete response rateChest X-ray abnormalitiesDoxorubicin/cyclophosphamidePhase I toxicityComplete response rateImmune checkpoint inhibitorsPhase I portionRelated adverse eventsPhase II portionPhase I partX-ray abnormalitiesNegative breast cancerSequential taxaneAnthracycline chemotherapyCheckpoint inhibitorsII trialAdverse eventsNew Therapeutic Strategies for Triple-Negative Breast Cancer.
Székely B, Silber AL, Pusztai L. New Therapeutic Strategies for Triple-Negative Breast Cancer. Oncology 2017, 31: 130-7. PMID: 28205193.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerResidual cancerBreast cancerEarly-stage triple-negative breast cancerUnselected triple negative breast cancerIntroduction of taxanesOngoing adjuvant trialsImmune checkpoint inhibitorsSurvival of patientsImportant clinical trialsImportant therapeutic advanceBRCA-mutant cancersNew therapeutic strategiesAntibody-drug conjugatesAdjuvant trialsNeoadjuvant chemotherapyAdjuvant therapyCheckpoint inhibitorsIdentifies patientsTherapeutic advancesClinical trialsHigh riskTherapeutic strategiesCancerTrials
2016
New Strategies in Breast Cancer: Immunotherapy
Pusztai L, Karn T, Safonov A, Abu-Khalaf MM, Bianchini G. New Strategies in Breast Cancer: Immunotherapy. Clinical Cancer Research 2016, 22: 2105-2110. PMID: 26867935, PMCID: PMC9359478, DOI: 10.1158/1078-0432.ccr-15-1315.Peer-Reviewed Original ResearchConceptsBreast cancerClinical trialsEffective immune checkpoint inhibitorsObjective tumor response rateEstrogen receptor-positive cancersLocal antitumor immune responsePhase I clinical trialImmune checkpoint inhibitorsTumor response rateAntitumor immune responseReceptor-positive cancersTriple-negative cancersLocal immune microenvironmentHER2-positive cancersMost breast cancersNew treatment modalitiesCheckpoint inhibitorsDurable responsesL1 antibodyLymphocytic infiltrationImmune microenvironmentImmune infiltrationTreatment modalitiesImmune responsePreclinical studies
2015
Immunotherapy opportunities in breast cancer.
Pusztai L, Ladányi A, Székely B, Dank M. Immunotherapy opportunities in breast cancer. Magyar Onkológia 2015, 60: 34-40. PMID: 26934349.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseLocal anti-tumour immune responseBreast cancerImmune responseClinical trialsEffective immune checkpoint inhibitorsEarly-stage breast cancerTriple-negative breast cancerPhase I clinical trialImmune checkpoint inhibitorsTumor response rateExtensive lymphocytic infiltrationPD-L1 antibodiesDirect clinical evidenceBreast cancer patientsStage breast cancerNew treatment modalitiesNegative breast cancerCheckpoint inhibitorsChemotherapy regimensMetastatic settingNeoadjuvant chemotherapyLymphocytic infiltrationClinical benefitClinical evidence