2022
Predictive 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
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
2018
CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers
Pelekanou V, Villarroel-Espindola F, Schalper KA, Pusztai L, Rimm DL. CD68, CD163, and matrix metalloproteinase 9 (MMP-9) co-localization in breast tumor microenvironment predicts survival differently in ER-positive and -negative cancers. Breast Cancer Research 2018, 20: 154. PMID: 30558648, PMCID: PMC6298021, DOI: 10.1186/s13058-018-1076-x.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic AgentsBiomarkers, TumorBreastBreast NeoplasmsDisease-Free SurvivalFemaleGene Expression Regulation, NeoplasticHumansMacrophagesMatrix Metalloproteinase 9Middle AgedPatient SelectionPrognosisReceptors, Cell SurfaceReceptors, EstrogenRetrospective StudiesSurvival AnalysisTissue Array AnalysisTumor MicroenvironmentConceptsTumor-associated macrophagesOverall survivalQuantitative immunofluorescenceMacrophage markersBreast cancerHigh expressionPan-macrophage marker CD68Triple-negative breast cancerCD163/CD68Multiplexed quantitative immunofluorescenceImproved overall survivalProtein expressionWorse overall survivalPoor overall survivalMMP-9 protein expressionSubclass of patientsMacrophage-targeted therapiesMatrix metalloproteinase-9Tissue microarray formatMMP-9 proteinBreast tumor microenvironmentModulator of responseParaffin-embedded tissuesBreast cancer biomarkersCohort B
2015
Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial
Bianchini G, Pusztai L, Pienkowski T, Im YH, Bianchi GV, Tseng LM, Liu MC, Lluch A, Galeota E, Magazzù D, de la Haba-Rodríguez J, Oh DY, Poirier B, Pedrini JL, Semiglazov V, Valagussa P, Gianni L. Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial. Annals Of Oncology 2015, 26: 2429-2436. PMID: 26387142, DOI: 10.1093/annonc/mdv395.Peer-Reviewed Original Research
2013
A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories
Szekely B, Iwamoto T, Szasz AM, Qi Y, Matsuoka J, Symmans WF, Tokes AM, Kulka J, Swanton C, Pusztai L. A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. Breast Cancer Research And Treatment 2013, 138: 691-698. PMID: 23504136, DOI: 10.1007/s10549-013-2475-4.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmBreast NeoplasmsCell ProliferationChemotherapy, AdjuvantCohort StudiesDatabases, GeneticDNA Topoisomerases, Type IIDNA-Binding ProteinsFemaleForkhead Box Protein M1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticGenome, HumanHumansKi-67 AntigenPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsPrognosisReceptors, EstrogenSurvival RateTamoxifenConceptsGenomic grade indexGrade 2 cancersPrognostic valueProliferation scoreBreast cancerDistant metastasis-free survival curvesGrade 2Metastasis-free survival curvesER-positive breast cancerSystemic adjuvant therapyHigh expressionCohort of patientsHistological grade 2Intermediate-risk cancerPositive breast cancerSimilar prognostic valueGrade 2 tumorsHigh-risk groupGrade 1 cancersHistological grade groupsNon-significant trendWorse DMFSAdjuvant tamoxifenAdjuvant therapyWorse survival
2011
Melanoma 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 responseA clinically relevant gene signature in triple negative and basal-like breast cancer
Rody A, Karn T, Liedtke C, Pusztai L, Ruckhaeberle E, Hanker L, Gaetje R, Solbach C, Ahr A, Metzler D, Schmidt M, Müller V, Holtrich U, Kaufmann M. A clinically relevant gene signature in triple negative and basal-like breast cancer. Breast Cancer Research 2011, 13: r97. PMID: 21978456, PMCID: PMC3262210, DOI: 10.1186/bcr3035.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBasal-like triple-negative breast cancerBreast cancerPrognostic markerMolecular subtypesMultivariate analysisBasal-like molecular subtypeClaudin-low molecular subtypeBasal-like breast cancerAttractive novel therapeutic targetB cell presenceHigh expressionER-positive cancersHigh histological gradeHigher B cellsIL-8 pathwayIL-8 activityNegative breast cancerNew prognostic markerNovel therapeutic targetBiology-based therapiesNon-neoplastic cell populationsRelevant gene signaturesRoutine clinicopathological variablesResultsSeventy-three percent