2023
Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer
Takahashi M, Cortés J, Dent R, Pusztai L, McArthur H, Kümmel S, Denkert C, Park Y, Im S, Ahn J, Mukai H, Huang C, Chen S, Kim M, Jia L, Li X, Tryfonidis K, Karantza V, Iwata H, Schmid P. Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer. JAMA Network Open 2023, 6: e2342107. PMID: 37966841, PMCID: PMC10652156, DOI: 10.1001/jamanetworkopen.2023.42107.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAdultAntibodies, Monoclonal, HumanizedAsiaB7-H1 AntigenFemaleHumansMiddle AgedTriple Negative Breast NeoplasmsConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalPathologic complete responseChemotherapy groupNeoadjuvant chemotherapyBreast cancerNeoadjuvant pembrolizumabDefinitive surgeryComplete responseMAIN OUTCOMEEastern Cooperative Oncology Group performance statusCell death ligand 1 (PD-L1) statusDeath ligand 1 (PD-L1) statusTreatment-related adverse eventsNonmetastatic triple-negative breast cancerCycles of pembrolizumabPembrolizumab Plus ChemotherapyTumor PD-L1Unacceptable toxic effectsPD-L1 statusOverall survival analysisAdjuvant pembrolizumabEFS eventsEFS ratesDual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency
Stecklein S, Barlow W, Pusztai L, Timms K, Kennedy R, Logan G, Seitz R, Badve S, Gökmen-Polar Y, Porter P, Linden H, Tripathy D, Hortobagyi G, Godwin A, Thompson A, Hayes D, Sharma P. Dual Prognostic Classification of Triple-Negative Breast Cancer by DNA Damage Immune Response and Homologous Recombination Deficiency. JCO Precision Oncology 2023, 7: e2300197. PMID: 37972336, PMCID: PMC10681491, DOI: 10.1200/po.23.00197.Peer-Reviewed Original ResearchMeSH KeywordsDNA DamageHomologous RecombinationHumansImmunityPrognosisTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsTriple-negative breast cancerHomologous recombination deficiencyBreast cancerAdjuvant anthracycline-based chemotherapyTherapeutic vulnerabilitiesRecombination deficiencyDistinct therapeutic vulnerabilitiesAnthracycline-based chemotherapyImmune response signaturesDNA-damaging therapiesFavorable prognosisIntermediate prognosisWorse prognosisImmunologic microenvironmentImmune responseChemoresistant tumorsPrognostic classificationHeterogeneous diseasePrognosisHeterogeneous groupDistinct subgroupsTumorsCancerResponse signatureSimultaneous assessmentPitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer
Thagaard J, Broeckx G, Page D, Jahangir C, Verbandt S, Kos Z, Gupta R, Khiroya R, Abduljabbar K, Haab G, Acs B, Akturk G, Almeida J, Alvarado‐Cabrero I, Amgad M, Azmoudeh‐Ardalan F, Badve S, Baharun N, Balslev E, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Bouchmaa N, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Dahl A, Portela F, Deman F, Demaria S, Hansen J, Dudgeon S, Ebstrup T, Elghazawy M, Fernandez‐Martín C, Fox S, Gallagher W, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hauberg S, Hewitt S, Hida A, Horlings H, Husain Z, Hytopoulos E, Irshad S, Janssen E, Kahila M, Kataoka T, Kawaguchi K, Kharidehal D, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Kovács A, Laenkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Ly A, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Minhas F, Mittal S, Moore D, Mushtaq S, Nighat H, Papathomas T, Penault‐Llorca F, Perera R, Pinard C, Pinto‐Cardenas J, Pruneri G, Pusztai L, Rahman A, Rajpoot N, Rapoport B, Rau T, Reis‐Filho J, Ribeiro J, Rimm D, Roslind A, Vincent‐Salomon A, Salto‐Tellez M, Saltz J, Sayed S, Scott E, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Fineberg S, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, van Diest P, Verghese G, Viale G, Vieth M, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Zin R, Adams S, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Salgado R, Stovgaard E. Pitfalls in machine learning‐based assessment of tumor‐infiltrating lymphocytes in breast cancer: A report of the International Immuno‐Oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2023, 260: 498-513. PMID: 37608772, PMCID: PMC10518802, DOI: 10.1002/path.6155.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersHumansLymphocytes, Tumor-InfiltratingMachine LearningMammary Neoplasms, AnimalTriple Negative Breast NeoplasmsConceptsTumor-infiltrating lymphocytesTriple-negative breast cancerBreast cancerTIL assessmentHER2-positive breast cancerRoutine clinical managementTIL evaluationTumor-immune interactionsClinical managementDiscordant assessmentsClinical significancePrognostic biomarkerTIL quantificationCancerDaily practicePatientsTrialsTissue patternsAssessmentLymphocytesBiomarkersASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest
Kim L, Coman M, Pusztai L, Park T. ASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest. Annals Of Surgical Oncology 2023, 30: 6452-6453. DOI: 10.1245/s10434-023-13842-4.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleHumansImmunotherapyNeoadjuvant TherapyTriple Negative Breast NeoplasmsIntratumor 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 casesNeoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest
Kim L, Coman M, Pusztai L, Park T. Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest. Annals Of Surgical Oncology 2023, 30: 6441-6449. PMID: 37349612, DOI: 10.1245/s10434-023-13714-x.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCombined Modality TherapyHumansImmunotherapyNeoadjuvant TherapyTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerTumor mutational burdenBreast cancerAdjuvant therapyPathological complete response rateImmune checkpoint modulationComplete response rateExcellent clinical outcomesCombination immunochemotherapyNeoadjuvant immunotherapyNeoadjuvant settingNeoadjuvant chemotherapyOverall survivalPD-L1Checkpoint modulationClinical outcomesMajor trialsMutational burdenResponse rateCancer typesCancerTherapyBiomarkersOutcomesExciting advancesVariable 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 ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorCarcinoma, Non-Small-Cell LungHumansImmunohistochemistryLung NeoplasmsTriple Negative Breast NeoplasmsConceptsTriple-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 profilingCisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial
Rodler E, Sharma P, Barlow W, Gralow J, Puhalla S, Anders C, Goldstein L, Tripathy D, Brown-Glaberman U, Huynh T, Szyarto C, Godwin A, Pathak H, Swisher E, Radke M, Timms K, Lew D, Miao J, Pusztai L, Hayes D, Hortobagyi G. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2023, 24: 162-174. PMID: 36623515, PMCID: PMC9924094, DOI: 10.1016/s1470-2045(22)00739-2.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMedian progression-free survivalProgression-free survivalMetastatic breast cancerMetastatic triple-negative breast cancerGermline BRCA1/2Phase 2 trialVeliparib groupPlacebo groupPlatinum-based chemotherapyBreast cancerHomologous recombination deficiencyAdverse eventsPARP inhibitorsEligible patientsMetastatic diseaseEastern Cooperative Oncology Group performance statusBRCA mutation-associated breast cancerInvestigator-assessed progression-free survivalTreatment-related adverse eventsRecurrent triple-negative breast cancerAcademic clinical sitesAddition of veliparibCommon grade 3Lines of chemotherapy
2022
Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021
Chehayeb R, Hood A, Wang X, Miksad R, Mougalian S, Lustberg M, Wang S, Greenup R, Pusztai L, Kunst N. Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021. JAMA Network Open 2022, 5: e2244204. PMID: 36445704, PMCID: PMC9709649, DOI: 10.1001/jamanetworkopen.2022.44204.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overBlack or African AmericanCost-Benefit AnalysisDrug CostsFemaleHumansMedicareMiddle AgedTriple Negative Breast NeoplasmsUnited StatesConceptsMetastatic breast cancerErbB2-positive metastatic breast cancerHR-positive metastatic breast cancerLines of therapyMBC subtypesDrug costsBreast cancerMedical costsHuman epidermal growth factor receptor 2 receptor statusMBC treatmentERBB2-negative metastatic breast cancerAssociated direct medical costsEarly-stage breast cancerHormone receptorsFlatiron Health databaseMetastatic recurrence ratesDifferent drug regimensBreast cancer careData of patientsDirect medical costsNovel adjuvant therapySupportive care drugsOutcomes of interestCost-effectiveness analysisAdjuvant therapyClinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm DL, Pusztai L. Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. Clinical Cancer Research 2022, 28: 3720-3728. PMID: 35903931, PMCID: PMC9444984, DOI: 10.1158/1078-0432.ccr-22-0862.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkersBreast NeoplasmsFemaleHumansNeoadjuvant TherapyTriple Negative Breast NeoplasmsConceptsImmune-related adverse eventsTriple-negative breast cancerNon-AA patientsEvent-free survivalPhase I/II clinical trialsClinical trialsNeoadjuvant chemotherapyOverall survivalAA patientsEarly-stage triple-negative breast cancerIncidence of irAEsPathologic complete response rateSignificant associationMultivariate logistic regression analysisTumor-infiltrating lymphocyte countsComplete response ratePrimary efficacy endpointPD-L1 statusProportional hazards modelLogistic regression analysisAfrican American womenEFS ratesNeoadjuvant immunotherapyEfficacy endpointAdverse eventsBiomarkers 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 ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantFemaleHumansMiddle AgedProspective StudiesReceptor, ErbB-2Retrospective StudiesTriple Negative Breast NeoplasmsConceptsBreast 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 cycleLCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer
Pérez-Núñez I, Rozalén C, Palomeque JÁ, Sangrador I, Dalmau M, Comerma L, Hernández-Prat A, Casadevall D, Menendez S, Liu DD, Shen M, Berenguer J, Ruiz IR, Peña R, Montañés JC, Albà MM, Bonnin S, Ponomarenko J, Gomis RR, Cejalvo JM, Servitja S, Marzese DM, Morey L, Voorwerk L, Arribas J, Bermejo B, Kok M, Pusztai L, Kang Y, Albanell J, Celià-Terrassa T. LCOR mediates interferon-independent tumor immunogenicity and responsiveness to immune-checkpoint blockade in triple-negative breast cancer. Nature Cancer 2022, 3: 355-370. PMID: 35301507, DOI: 10.1038/s43018-022-00339-4.Peer-Reviewed Original ResearchMeSH KeywordsHumansImmune Checkpoint InhibitorsImmunotherapyInterferonsMelanomaRepressor ProteinsSkin NeoplasmsTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerCancer stem cellsLigand-dependent corepressorTumor immunogenicityBreast cancerImmune checkpoint blockadeBreast cancer metastasisICB efficacyICB resistanceLCoR expressionClinical responsePresentation machineryImmune escapeAPM genesPreclinical modelsTherapy resistanceCancer metastasisPromising targetOvercame resistanceIFNRNA therapyCancerImmunogenicitySignaling-independent mannerStem cellsEvent-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer
Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O'Shaughnessy J. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal Of Medicine 2022, 386: 556-567. PMID: 35139274, DOI: 10.1056/nejmoa2112651.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantFemaleHumansIntention to Treat AnalysisKaplan-Meier EstimateMiddle AgedNeoadjuvant TherapyProgression-Free SurvivalTriple Negative Breast NeoplasmsConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalCycles of pembrolizumabPathological complete responseDefinitive surgeryBreast cancerNeoadjuvant chemotherapyComplete responseLonger event-free survivalUntreated stage IIPrimary end pointPhase 3 trialSecond primary cancerDoxorubicin-cyclophosphamideNeoadjuvant pembrolizumabNeoadjuvant phaseAdjuvant therapyDistant recurrenceNeoadjuvant therapyAdverse eventsPrimary cancerSafety profileDisease progressionPembrolizumab
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 ResearchMeSH KeywordsBiomarkers, TumorBlack or African AmericanCase-Control StudiesHumansTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsNegative 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 levelPatientsTNBCTumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer
Gonzalez-Ericsson PI, Wulfkhule JD, Gallagher RI, Sun X, Axelrod ML, Sheng Q, Luo N, Gomez H, Sanchez V, Sanders M, Pusztai L, Petricoin E, Blenman K, Balko JM, Team I, Leyland-Jones B, Agency C, Chia S, Serpanchy R, Yu C, University E, McMillan S, Mosley R, Nguyen K, Wood E, Zelnak A, University G, Dillis C, Donnelly R, Harrington T, Isaacs C, Kallakury B, Liu M, Lynce F, Oppong B, Pohlmann P, Tousimis E, Warren R, Willey S, Wong J, Zeck J, Center L, Albain K, Bartolotta M, Bova D, Brooks C, Busby B, Czaplicki K, Duan X, Gamez R, Ganesh K, Gaynor E, Godellas C, Grace-Louthen C, Kuritza T, Lo S, Nagamine A, Perez C, Robinson P, Rosi D, Vaince F, Ward K, Hospital I, Choquette K, Edmiston K, Gallimore H, McGovern J, Mokarem K, Pajaniappan M, Rassulova S, Scott K, Sherwood K, Wright J, Clinic A, Anderson K, Gray R, Myers S, Northfelt D, Pockaj B, Roedig J, Wasif N, Clinic R, Arens A, Boughey J, Brandt K, Carroll J, Chen B, Connors A, Degnim A, Farley D, Greenlee S, Haddad T, Hieken T, Hobday T, Jakub J, Liberte L, Liu M, Loprinzi C, Menard L, Moe M, Moynihan T, O'Sullivan C, Olson E, Peethambaram P, Ruddy K, Russell B, Rynearson A, Smith D, Visscher D, Windish A, Institute H, Cox K, Dawson K, Newton O, Ramirez W, University O, Bengtson H, Bucher J, Chui S, Gilbert-Ghormley B, Hampton R, Kemmer K, Kurdyla D, Nauman D, Spear J, Wilson A, Institute S, Beatty D, Dawson P, Ellis E, Fer M, Hanson J, Goetz M, Haddad T, Iriarte D, Kaplan H, Porter B, Rinn K, Thomas H, Thornton S, Tickman R, Varghis N, Birmingham U, Caterinichia V, Santos J, Falkson C, Forero A, Krontiras H, Vaklavas C, Wei S, University of Arizona, Bauland A, Inclan L, Lewallen D, Powell A, Roney C, Schmidt K, Viscusi R, Wright H, University of California S, Blair S, Boles S, Bykowski J, Datnow B, Densley L, Eghtedari M, Genna V, Hasteh F, Helsten T, Kormanik P, Ojeda-Fournier H, Onyeacholem I, Parker B, Podsada K, Schwab R, Wallace A, Yashar C, University of California S, Alvarado M, Au A, Balassanian R, Benz C, Buxton M, Chen Y, Chien J, D'Andrea C, Davis S, Esserman L, Ewing C, Goga A, Hirst G, Hwang M, Hylton N, Joe B, Lyandres J, Kadafour M, Krings G, Melisko M, Moasser M, Munter P, Ngo Z, Park J, Price E, Rugo H, Veer L, Wong J, Yau C, University of Chicago, Abe H, Jaskowiak N, Nanda R, Olopade F, Schacht D, University of Colorado D, Borges V, Colvin T, Diamond J, Elias A, Finlayson C, Fisher C, Hardesty L, Kabos P, Kounalakis N, Mayordomo J, McSpadden T, Murphy C, Rabinovitch R, Sams S, Shagisultanova E, University of Kansas, Baccaray S, Khan Q, University of Minnesota, Beckwith H, Blaes A, Emory T, Haddad T, Hui J, Klein M, Kuehn-Hajder J, Nelson M, Potter D, Tuttle T, Yee D, Zera R, University of Pennsylvania, Bayne L, Bradbury A, Clark A, DeMichele A, Domchek S, Fisher C, Fox K, Frazee D, Lackaye M, Matro J, McDonald E, Rosen M, Shah P, Tchou J, Volpe M, Center U, Alvarez R, Barcenas C, Berry D, Booser D, Brewster A, Brown P, Gonzalez-Angulo A, Ibrahim N, Karuturi M, Koenig K, Moulder S, Murray J, Murthy R, Pusztai L, Saigal B, Symmans W, Tripathy D, Theriault R, Ueno N, Valero V, California U, Brown M, Carranza M, Flores Y, Lang J, Luna A, Perez N, Tripathy D, Watkins K, Center U, Armstrong S, Boyd C, Chen L, Clark V, Frankel A, Euhus D, Froehlich T, Goudreau S, Haley B, Harker-Murray A, Klemow D, Leitch A, Leon R, Li H, Morgan T, Qureshi N, Rao R, Reeves M, Rivers A, Sadeghi N, Seiler S, Staves B, Tagoe V, Thomas G, Tripathy D, Unni N, Weyandt S, Wooldridge R, Zuckerman J, Universty of Washington, Korde L, Griffin M, Butler B, Cundy A, Rubinstein L, Hixson C. Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer. Clinical Cancer Research 2021, 27: 5299-5306. PMID: 34315723, PMCID: PMC8792110, DOI: 10.1158/1078-0432.ccr-21-0607.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHistocompatibilityHumansNeoadjuvant TherapyReceptor, ErbB-2Retrospective StudiesTriple Negative Breast NeoplasmsConceptsStandard neoadjuvant chemotherapyTriple-negative breast cancerNeoadjuvant chemotherapyBreast cancerMHC-IITumor cellsAnti-PD-1/L1 therapyEstrogen receptor-positive breast cancerPhase II/III clinical trialsNeoadjuvant breast cancer settingPathologic complete response rateHER2-negative breast cancerReceptor-positive breast cancerAddition of immunotherapyHLA-DR positivityBreast cancer settingComplete response rateHER2-negative patientsCohort of patientsEarly breast cancerMHC-II expressionPan-cancer biomarkerImmunotherapy benefitL1 therapyMost patientsClinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases
Huang RSP, Haberberger J, McGregor K, Mata DA, Decker B, Hiemenz MC, Lechpammer M, Danziger N, Schiavone K, Creeden J, Graf RP, Strowd R, Lesser GJ, Razis ED, Bartsch R, Giannoudis A, Bhogal T, Lin NU, Pusztai L, Ross JS, Palmieri C, Ramkissoon SH. Clinicopathologic and Genomic Landscape of Breast Carcinoma Brain Metastases. The Oncologist 2021, 26: 835-844. PMID: 34105210, PMCID: PMC8488784, DOI: 10.1002/onco.13855.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBrain NeoplasmsGenomicsHumansRetrospective StudiesTriple Negative Breast NeoplasmsConceptsComprehensive genomic profilingPD-L1 immunohistochemistryBrain metastasesTumor mutational burdenPrimary breast carcinomaRelevant genomic alterationsBreast carcinomaPrimary tumorHigh prevalenceMutational burdenCerebrospinal fluidTissue acquisitionCatalytic polypeptide-like (APOBEC) mutational signatureGenomic alterationsPrimary breast carcinoma specimensHigh tumor mutational burdenGenomic profilingTriple-negative breast carcinomaTNBC brain metastasisCohort of patientsBrain metastasis samplesBreast carcinoma specimensHigher positive rateHigh microsatellite instabilityApolipoprotein B mRNA editing enzyme
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 ResearchMeSH KeywordsAdultAgedAged, 80 and overB7-H1 AntigenFemaleHumansMiddle AgedNeoplasm MetastasisRetrospective StudiesTriple Negative Breast NeoplasmsConceptsPD-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 coefficientPD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expressionBiomarkers 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 ResearchMeSH KeywordsB7-H1 AntigenBiomarkers, TumorGenomicsHumansImmunohistochemistryTriple Negative Breast NeoplasmsConceptsComprehensive 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