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 casesVariable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay
Danziger N, Sokol E, Graf R, Hiemenz M, Maule J, Parimi V, Palmieri C, Pusztai L, Ross J, Huang R. Variable Landscape of PD-L1 Expression in Breast Carcinoma as Detected by the DAKO 22C3 Immunohistochemistry Assay. The Oncologist 2023, 28: 319-326. PMID: 36866462, PMCID: PMC10078903, DOI: 10.1093/oncolo/oyad025.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerPD-L1 expressionNegative triple negative breast cancerTNBC tissue samplesPD-L1 positivityPD-L1Dako 22C3Breast cancerDeath ligand 1 (PD-L1) immunohistochemistry (IHC) assaysPD-L1 groupNon-TNBC patientsTissue samplesComprehensive genomic profilingBreast cancer subtypesFoundationOne CDxImmunotherapy efficacyMetastatic sitesTNBC casesBC patientsBreast carcinomaPositive statusImmunohistochemistry assaysOptimum cutoffCancer subtypesGenomic profiling
2022
PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer
Rozenblit M, Blenman K, Harigopal M, Reisenbichler E, Singh K, Qing T, Ibrahim E, Ramkissoon S, Asmelash S, Lin HK, Roberts M, Ross J, Huang RSP, Pusztai L. PD-L1 protein expression in relation to recurrence score values in early-stage ER + breast cancer. Breast Cancer Research And Treatment 2022, 196: 221-227. PMID: 36028784, DOI: 10.1007/s10549-022-06712-2.Peer-Reviewed Original ResearchConceptsPD-L1 positivityPD-L1 protein expressionPD-L1 expressionGrade 3 cancersPD-L1TIL scoreTumor gradeMultivariate analysisHigher PD-L1 positivityTumor-infiltrating lymphocyte countsConclusionPD-L1 expressionProtein expressionPD-L1 immunohistochemistryChi-square testResultsPD-L1T1 cancersLymphocyte countT3 tumorsIndependent predictorsTumor sizeLarge tumorsPositivity rateCell positivityBreast cancerGrade 2
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 inhibitors
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 coefficientBiomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer
Huang RSP, Li X, Haberberger J, Sokol E, Severson E, Duncan DL, Hemmerich A, Edgerly C, Williams E, Elvin J, Vergilio J, Killian J, Lin D, Hiemenz M, Xiao J, McEwan D, Holmes O, Danziger N, Erlich R, Frampton G, Cohen M, McGregor K, Reddy P, Cardeiro D, Anhorn R, Venstrom J, Alexander B, Brown C, Pusztai L, Ross J, Ramkissoon S. Biomarkers in Breast Cancer: An Integrated Analysis of Comprehensive Genomic Profiling and PD‐L1 Immunohistochemistry Biomarkers in 312 Patients with Breast Cancer. The Oncologist 2020, 25: 943-953. PMID: 32869930, PMCID: PMC7648336, DOI: 10.1634/theoncologist.2020-0449.Peer-Reviewed Original ResearchConceptsComprehensive genomic profilingPD-L1 immunohistochemistryPotential therapeutic optionBreast cancerPD-L1Therapeutic optionsTriple negative breast cancer cohortDrug AdministrationHormone receptor-positive breast cancerReceptor-positive breast cancerGenomic profilingTriple-negative breast cancerPD-L1 positivityRoutine clinical careMutations/MbBreast cancer cohortBiomarker landscapeTNBC cohortNab-paclitaxelGermline testingConsecutive patientsReceptor negativeHER2-positiveClinical trialsPIK3CA mutations
2018
Immunological differences between primary and metastatic breast cancer
Szekely B, Bossuyt V, Li X, Wali VB, Patwardhan GA, Frederick C, Silber A, Park T, Harigopal M, Pelekanou V, Zhang M, Yan Q, Rimm DL, Bianchini G, Hatzis C, Pusztai L. Immunological differences between primary and metastatic breast cancer. Annals Of Oncology 2018, 29: 2232-2239. PMID: 30203045, DOI: 10.1093/annonc/mdy399.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAntineoplastic Agents, ImmunologicalB7-H1 AntigenBiomarkers, TumorBiopsyBreast NeoplasmsDisease ProgressionDrug Resistance, NeoplasmFemaleGene Expression RegulationHumansImmunologic SurveillanceLymphocyte CountLymphocytes, Tumor-InfiltratingMiddle AgedMutation RateTumor EscapeTumor MicroenvironmentYoung AdultConceptsMetastatic breast cancerBreast cancerTherapeutic targetToll-like receptor pathway genesImmuno-oncology therapeutic targetsBreast cancer evolvesImmune proteasome expressionPD-L1 positivityCorresponding primary tumorsPotential therapeutic targetMHC class IImmune-related genesMetastatic cancer samplesLigand/receptor pairLymphocyte countT helperT-regsPD-L1Immune microenvironmentCytotoxic TPrimary tumorMastoid cellsDisease progressionTherapeutic combinationsMacrophage markers