2024
Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer
Jahangir C, Page D, Broeckx G, Gonzalez C, Burke C, Murphy C, Reis‐Filho J, Ly A, Harms P, Gupta R, Vieth M, Hida A, Kahila M, Kos Z, van Diest P, Verbandt S, Thagaard J, Khiroya R, Abduljabbar K, Haab G, Acs B, Adams S, Almeida J, Alvarado‐Cabrero I, Azmoudeh‐Ardalan F, Badve S, Baharun N, Bellolio E, Bheemaraju V, Blenman K, Fujimoto L, Burgues O, Chardas A, Cheang M, Ciompi F, Cooper L, Coosemans A, Corredor G, Portela F, Deman F, Demaria S, Dudgeon S, Elghazawy M, Fernandez‐Martín C, Fineberg S, Fox S, Giltnane J, Gnjatic S, Gonzalez‐Ericsson P, Grigoriadis A, Halama N, Hanna M, Harbhajanka A, Hart S, Hartman J, Hewitt S, Horlings H, Husain Z, Irshad S, Janssen E, Kataoka T, Kawaguchi K, Khramtsov A, Kiraz U, Kirtani P, Kodach L, Korski K, Akturk G, Scott E, Kovács A, Lænkholm A, Lang‐Schwarz C, Larsimont D, Lennerz J, Lerousseau M, Li X, Madabhushi A, Maley S, Narasimhamurthy V, Marks D, McDonald E, Mehrotra R, Michiels S, Kharidehal D, 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, Rajpoot N, Rapoport B, Rau T, Ribeiro J, Rimm D, Vincent‐Salomon A, Saltz J, Sayed S, Hytopoulos E, Mahon S, Siziopikou K, Sotiriou C, Stenzinger A, Sughayer M, Sur D, Symmans F, Tanaka S, Taxter T, Tejpar S, Teuwen J, Thompson E, Tramm T, Tran W, van der Laak J, Verghese G, Viale G, Wahab N, Walter T, Waumans Y, Wen H, Yang W, Yuan Y, Bartlett J, Loibl S, Denkert C, Savas P, Loi S, Stovgaard E, Salgado R, Gallagher W, Rahman A. Image‐based multiplex immune profiling of cancer tissues: translational implications. A report of the International Immuno‐oncology Biomarker Working Group on Breast Cancer. The Journal Of Pathology 2024, 262: 271-288. PMID: 38230434, PMCID: PMC11288342, DOI: 10.1002/path.6238.Peer-Reviewed Original ResearchConceptsImmune profileInternational Immuno-Oncology Biomarker Working GroupIdentification of clinically relevant biomarkersField of immuno-oncologyBiomarker Working GroupManagement of cancer patientsImmune profiling of tumorsClinical trial perspectiveTranslational implicationsProfiling of tumorsIndividual tumor cellsPredicting disease prognosisClinically relevant biomarkersSubtypes of cancerImmuno-oncologyTumor microenvironmentMultiplex immunohistochemistryTreatment responseTumor cellsBreast cancerTumor samplesCancer patientsTreatment choiceDisease prognosisRelevant biomarkers
2023
Biomarkers predicting response to 5 immunotherapy arms in the neoadjuvant I-SPY2 trial for early-stage breast cancer (BC): Evaluation of immune subtyping in the response predictive subtypes (RPS).
Wolf D, Yau C, Campbell M, Glas A, Mittempergher L, Kuilman M, Barcaru A, Brown Swigart L, Nanda R, Chien A, Pusztai L, Stringer-Reasor E, Shatsky R, Isaacs C, Perlmutter J, DeMichele A, Yee D, Esserman L, van 't Veer L. Biomarkers predicting response to 5 immunotherapy arms in the neoadjuvant I-SPY2 trial for early-stage breast cancer (BC): Evaluation of immune subtyping in the response predictive subtypes (RPS). Journal Of Clinical Oncology 2023, 41: 102-102. DOI: 10.1200/jco.2023.41.16_suppl.102.Peer-Reviewed Original ResearchPCR rateBreast cancerImmune markersSerious immune-related adverse eventsImmune-related adverse eventsHER2-negative breast cancerEarly-stage breast cancerI-SPY2 trialLower mast cellTumor immune signatureChemokines/cytokinesSingle-sample classifierImmune subtypingImmunotherapy armI-SPY2Therapy armAdverse eventsReceptor statusControl armDrug classesMast cellsLogistic regressionBenjamini-Hochberg methodHR subsetTumor cellsTumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer
Nanou A, Miao J, Coumans F, Dolce E, Darga E, Barlow W, Smerage J, Paoletti C, Godwin A, Pusztai L, Sharma P, Thompson A, Hortobagyi G, Terstappen L, Hayes D. Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast Cancer. JCO Precision Oncology 2023, 7: e2200372. PMID: 36634296, PMCID: PMC9928629, DOI: 10.1200/po.22.00372.Peer-Reviewed Original ResearchConceptsCycles of chemotherapyMetastatic breast cancerTumor-derived extracellular vesiclesOverall survivalBreast cancerTumor cellsExtracellular vesiclesComplementary prognostic factorComplementary prognostic valuePoor overall survivalAdditional prognostic biomarkerLonger OSPrognostic factorsPrognostic significanceCTC countPrognostic valuePrognostic biomarkerChemotherapyCancerPatientsCTCsCellsBiomarkers
2021
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
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 ResearchConceptsStandard 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 patients
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 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 expression
2019
Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer
Rimm DL, Han G, Taube JM, Yi ES, Bridge JA, Flieder DB, Homer R, Roden AC, Hirsch FR, Wistuba II, Pusztai L. Reanalysis of the NCCN PD-L1 companion diagnostic assay study for lung cancer in the context of PD-L1 expression findings in triple-negative breast cancer. Breast Cancer Research 2019, 21: 72. PMID: 31196152, PMCID: PMC6567382, DOI: 10.1186/s13058-019-1156-6.Peer-Reviewed Original ResearchConceptsPD-L1 expressionImmune cell PD-L1 expressionLung cancerImmune cellsTriple-negative breast cancerEasy scoring methodCompanion diagnostic testsPD-L1Immune therapyBreast cancerImmunohistochemical testsBetter outcomesLarger studyTumor cellsDiagnostic testsCancerExpression findingsCellsExpressionPoor agreementScoring methodTherapyTrials
2014
Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy
Sistigu A, Yamazaki T, Vacchelli E, Chaba K, Enot DP, Adam J, Vitale I, Goubar A, Baracco EE, Remédios C, Fend L, Hannani D, Aymeric L, Ma Y, Niso-Santano M, Kepp O, Schultze JL, Tüting T, Belardelli F, Bracci L, La Sorsa V, Ziccheddu G, Sestili P, Urbani F, Delorenzi M, Lacroix-Triki M, Quidville V, Conforti R, Spano JP, Pusztai L, Poirier-Colame V, Delaloge S, Penault-Llorca F, Ladoire S, Arnould L, Cyrta J, Dessoliers MC, Eggermont A, Bianchi ME, Pittet M, Engblom C, Pfirschke C, Préville X, Uzè G, Schreiber RD, Chow MT, Smyth MJ, Proietti E, André F, Kroemer G, Zitvogel L. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nature Medicine 2014, 20: 1301-1309. PMID: 25344738, DOI: 10.1038/nm.3708.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsAnthracyclinesBreast NeoplasmsChemokine CXCL10DoxorubicinFemaleGene Expression Regulation, NeoplasticHumansImmunocompetenceInterferon Type IMice, Inbred C57BLMyxovirus Resistance ProteinsNeoadjuvant TherapyNeoplasm MetastasisReceptor, Interferon alpha-betaReceptors, Pattern RecognitionRNARNA, MessengerSignal TransductionToll-Like Receptor 3Treatment Outcome
2011
P4-03-04: Identification of Molecular Targets for Cancer-Initiating Cells Using a Triple-Negative Breast Cancer Mouse Model.
Kai K, Iwamoto T, Pusztai L, Hortobagyi G, Saya H, Ueno N. P4-03-04: Identification of Molecular Targets for Cancer-Initiating Cells Using a Triple-Negative Breast Cancer Mouse Model. Cancer Research 2011, 71: p4-03-04-p4-03-04. DOI: 10.1158/0008-5472.sabcs11-p4-03-04.Peer-Reviewed Original ResearchTriple-negative breast cancerTumor-initiating activityCancer-initiating cellsHuman triple-negative breast cancerTNBC mouse modelMammary fat padHigh tumor-initiating activityMouse modelTumor cellsRecipient miceClinical aggressivenessBreast cancerMouse mammary epithelial cellsFat padTriple-negative breast cancer mouse modelBackground Triple-negative breast cancerBreast cancer mouse modelAnti-HER2 agentsMouse mammary fat padMolecular profileBreast cancer subtypesCancer mouse modelEndothelin-A receptorExpression levelsCancer initiating cellsArtificial neural network analysis of circulating tumor cells in metastatic breast cancer patients
Giordano A, Giuliano M, De Laurentiis M, Eleuteri A, Iorio F, Tagliaferri R, Hortobagyi GN, Pusztai L, De Placido S, Hess K, Cristofanilli M, Reuben JM. Artificial neural network analysis of circulating tumor cells in metastatic breast cancer patients. Breast Cancer Research And Treatment 2011, 129: 451-458. PMID: 21710134, DOI: 10.1007/s10549-011-1645-5.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBreast NeoplasmsFemaleHumansImmunohistochemistryKaplan-Meier EstimateLinear ModelsMiddle AgedNeoplastic Cells, CirculatingNeural Networks, ComputerPrognosisProportional Hazards ModelsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesRisk AssessmentRisk FactorsSurvival RateTexasTime FactorsConceptsMetastatic breast cancer patientsRisk of deathBreast cancer patientsCTC countMBC patientsPrognostic effectCancer patientsTumor subtypesTumor cellsMD Anderson Cancer CenterConsecutive MBC patientsTriple-negative MBCMetastatic disease sitesAnderson Cancer CenterTumor molecular subtypeNumber of CTCsMolecular tumor subtypesVisceral metastasesOverall survivalCancer CenterHER2 statusProgesterone receptorMolecular subtypesTherapy typePrognostic tool
2008
Residual specimen cellularity after neoadjuvant chemotherapy for breast cancer
Peintinger F, Kuerer HM, McGuire SE, Bassett R, Pusztai L, Symmans WF. Residual specimen cellularity after neoadjuvant chemotherapy for breast cancer. British Journal Of Surgery 2008, 95: 433-437. PMID: 18161887, DOI: 10.1002/bjs.6044.Peer-Reviewed Original ResearchConceptsResidual tumour cellularityNeoadjuvant chemotherapyBreast-conserving surgeryResidual cellularityBreast cancerTumor cellularityIntraoperative marginsInitial breast-conserving surgeryResidual invasive breast cancerInvasive breast cancerPrimary tumor areaInvasive lobular carcinomaFalse-negative marginsCent of specimensInvasive tumor cellsLobular carcinomaMargin rateChemotherapyPatientsPathology slidesCellularityTumor areaSurgeryTumor cellsCancer
2007
New Generation of Molecular Prognostic and Predictive Tests for Breast Cancer
Pusztai L, Cristofanilli M, Paik S. New Generation of Molecular Prognostic and Predictive Tests for Breast Cancer. Seminars In Oncology 2007, 34: s10-s16. PMID: 17512431, DOI: 10.1053/j.seminoncol.2007.03.015.Peer-Reviewed Original ResearchConceptsBreast cancerBreast cancer careDifferent clinical coursesAvailable diagnostic assaysTrial-based approachClinical coursePrognostic predictorCancer carePrognostic informationSimilar tumorsMolecular PrognosticHeterogeneous diseaseTumor cellsCancerPredictive testDiagnostic assaysNovel diagnosticsMolecular analytical techniquesMolecular differencesImportant advancesMolecular analysisPatientsDiagnostic companiesTumorsDisease
1998
Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells.
Dean G, Pusztai L, Xu F, O'Briant K, DeSombre K, Conaway M, Boyer C, Mendelsohn J, Bast R. Cell surface density of p185(c-erbB-2) determines susceptibility to anti-p185(c-erbB-2)-ricin A chain (RTA) immunotoxin therapy alone and in combination with anti-p170(EGFR)-RTA in ovarian cancer cells. Clinical Cancer Research 1998, 4: 2545-50. PMID: 9796989.Peer-Reviewed Original ResearchConceptsOvarian cancer cellsReceptors/cellCancer cellsC-erbBSynergistic cytotoxicityCopies/cellTumor cellsSKOV3 human ovarian cancer cellsHuman ovarian cancer cellsClonogenic tumor cellsCell surface densityBreast cancerRTA immunotoxinsNude miceSame immunotoxinFirst treatmentAnchorage-independent growthAnchorage-dependent growthVivo growthClonogenic cellsImmunotoxinExpression levelsSignificant correlationCell linesNormal cellsCoexpression of the HER-2 Gene Product, pl85HER-2, and Epidermal Growth Factor Receptor, pl70EGF-R, on Epithelial Ovarian Cancers and Normal Tissues
Bast R, Pusztai L, Kerns B, MacDonald J, Jordan P, Daly L, Boyer C, Mendelsohn J, Berchuck A. Coexpression of the HER-2 Gene Product, pl85HER-2, and Epidermal Growth Factor Receptor, pl70EGF-R, on Epithelial Ovarian Cancers and Normal Tissues. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 1998, 17: 313-321. PMID: 9790065, DOI: 10.1089/hyb.1998.17.313.Peer-Reviewed Original ResearchConceptsOvarian cancerNormal ovarian epitheliumNormal tissuesOvarian epitheliumTumor cellsAdvanced ovarian cancerEpithelial ovarian cancerFavorable therapeutic indexCombination of antibodiesEpidermal growth factor receptorGrowth factor receptorEpithelial specimensHER-2Normal ovariesP170 expressionP185 expressionTherapeutic indexNeoplastic cellsTumor growthSynergistic cytotoxicityFrozen sectionsCancerTherapeutic activityDifferent antigensMonoclonal antibodies