2024
Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial
Khoury K, Meisel J, Yau C, Rugo H, Nanda R, Davidian M, Tsiatis B, Chien A, Wallace A, Arora M, Rozenblit M, Hershman D, Zimmer A, Clark A, Beckwith H, Elias A, Stringer-Reasor E, Boughey J, Nangia C, Vaklavas C, Omene C, Albain K, Kalinsky K, Isaacs C, Tseng J, Roussos Torres E, Thomas B, Thomas A, Sanford A, Balassanian R, Ewing C, Yeung K, Sauder C, Sanft T, Pusztai L, Trivedi M, Outhaythip A, Li W, Onishi N, Asare A, Beineke P, Norwood P, Brown-Swigart L, Hirst G, Matthews J, Moore B, Fraser Symmans W, Price E, Beedle C, Perlmutter J, Pohlmann P, Shatsky R, DeMichele A, Yee D, van ‘t Veer L, Hylton N, Esserman L. Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. Nature Medicine 2024, 1-9. PMID: 39277671, DOI: 10.1038/s41591-024-03266-2.Peer-Reviewed Original ResearchBreast cancerLikelihood of pathologic complete responseTreatment strategiesPathologic complete response rateEarly-stage breast cancerEarly surgical resectionTaxane-based regimenComplete response ratePathological complete responsePhase 2 trialBreast cancer subtypesEffective personalized treatmentHigh-risk stageMagnetic resonance imagingComplete responseDoxorubicin-cyclophosphamideNeoadjuvant treatmentSurgical resectionOcular eventsEfficacy analysisPrimary endpointTumor subtypesNew agentsCancer subtypesPatients
2023
Variable 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
Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies
Wolf DM, Yau C, Wulfkuhle J, Brown-Swigart L, Gallagher RI, Lee PRE, Zhu Z, Magbanua MJ, Sayaman R, O’Grady N, Basu A, Delson A, Coppé JP, Lu R, Braun J, Investigators I, Asare SM, Sit L, Matthews JB, Perlmutter J, Hylton N, Liu MC, Pohlmann P, Symmans WF, Rugo HS, Isaacs C, DeMichele AM, Yee D, Berry DA, Pusztai L, Petricoin EF, Hirst GL, Esserman LJ, van 't Veer LJ. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell 2022, 40: 609-623.e6. PMID: 35623341, PMCID: PMC9426306, DOI: 10.1016/j.ccell.2022.05.005.Peer-Reviewed Original ResearchConceptsBreast cancer subtypesHormone receptorsHuman epidermal growth factor receptor 2 (HER2) statusCancer subtypesEpidermal growth factor receptor 2 statusPathologic complete response rateTreatment prioritizationComplete response ratePatient selectionPredictive biomarkersTreatment allocationPlatform trialsClinical dataLuminal phenotypeTreatment selectionResponse rateTumor biologyNew treatmentsDrug responseSubtypesCancer therapyBiomarkersProtein/phosphoproteinGene expressionDiverse biology
2021
Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients
Yau C, Osdoit M, van der Noordaa M, Shad S, Wei J, de Croze D, Hamy AS, Laé M, Reyal F, Sonke GS, Steenbruggen TG, van Seijen M, Wesseling J, Martín M, del Monte-Millán M, López-Tarruella S, Consortium I, Adamson K, Albain K, Asare A, Asare S, Balassanian R, Beckwith H, Berry S, Berry D, Boughey J, Buxton M, Chen Y, Chen B, Chien A, Chui S, Clark A, Clennell J, Datnow B, DeMichele A, Duan X, Edmiston K, Elias A, Ellis E, Esserman L, Euhus D, Fadare O, Fan F, Feldman M, Forero-Torres A, Haley B, Han H, Harada S, Haugen P, Helsten T, Hirst G, Hylton N, Isaacs C, Kemmer K, Khan Q, Khazai L, Klein M, Krings G, Lang J, LeBeau L, Leyland-Jones B, Liu M, Lo S, Lu J, Magliocco A, Matthews J, Melisko M, Mhawech-Fauceglia P, Moulder S, Murthy R, Nanda R, Northfelt D, Ocal I, Olopade O, Pambuccian S, Paoloni M, Park J, Parker B, Perlmutter J, Peterson G, Pusztai L, Rendi M, Rugo H, Sahoo S, Sams S, Sanil A, Sattar H, Schwab R, Singhrao R, Steeg K, Stringer-Reasor E, Symmans W, Tawfik O, Tripathy D, Troxell M, Veer L, Venters S, Vinh T, Viscusi R, Wallace A, Wei S, Wilson A, Yau C, Yee D, Zeck J, Boughey J, Goetz M, Hoskin T, Gould R, Valero V, Edge S, Abraham J, Bartlett J, Caldas C, Dunn J, Earl H, Hayward L, Hiller L, Provenzano E, Sammut S, Thomas J, Cameron D, Graham A, Hall P, Mackintosh L, Fan F, Godwin A, Schwensen K, Sharma P, DeMichele A, Cole K, Pusztai L, Kim M, van 't Veer L, Esserman L, Symmans W. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. The Lancet Oncology 2021, 23: 149-160. PMID: 34902335, PMCID: PMC9455620, DOI: 10.1016/s1470-2045(21)00589-1.Peer-Reviewed Original ResearchConceptsResidual cancer burdenEvent-free survivalRCB scoreHER2-positive groupNeoadjuvant chemotherapyBreast cancer subtypesBreast cancerHazard ratioCancer subtypesNodal statusCancer burdenT categoryEvent-free survival eventsPooled patient-level analysisLong-term survival outcomesPractice settingsWorse event-free survivalClinical T categoryHigher RCB scoresStandard pathology reportingHER2-negative patientsHormone receptor statusHER2-negative groupLong-term prognosisPrimary stage I
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 Res
2015
CCR 20th Anniversary Commentary: Divide and Conquer—Breast Cancer Subtypes and Response to Therapy
Pusztai L, Rouzier R, Symmans WF. CCR 20th Anniversary Commentary: Divide and Conquer—Breast Cancer Subtypes and Response to Therapy. Clinical Cancer Research 2015, 21: 3575-3577. PMID: 26275950, DOI: 10.1158/1078-0432.ccr-14-3121.Peer-Reviewed Original ResearchConceptsBreast cancerPathologic complete response rateTriple-negative breast cancerAdjuvant treatment optionsResidual invasive diseaseComplete response rateHER2-positive cancersDifferent molecular subtypesClin Cancer ResClinical cancer researchAnniversary CommentaryNeoadjuvant therapyTreatment optionsInvasive diseaseClinical trialsMolecular subtypesResponse rateCancer subtypesCancer ResExtent of responseCancerSubtypesTherapyCancer researchChemotherapy
2013
Correlation of intratumor gene expression heterogeneity with chemotherapy sensitivity in breast cancer.
Natowicz R, Jiang T, Shi W, Qi Y, Delpech Y, Symmans W, Pusztai L. Correlation of intratumor gene expression heterogeneity with chemotherapy sensitivity in breast cancer. Journal Of Clinical Oncology 2013, 31: 1013-1013. DOI: 10.1200/jco.2013.31.15_suppl.1013.Peer-Reviewed Original ResearchPathologic complete responseBasal-like cancersBreast cancerNeoadjuvant chemotherapyChemotherapy sensitivityCancer subtypesLuminal B cancersDifferent molecular subtypesBreast cancer subtypesB cancersComplete responseLuminal cancersResidual diseaseMolecular subtypesStage ICancerGene signatureGreat heterogeneitySubtypesTumor heterogeneityChemotherapySignificant differences
2012
Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes
Hanker LC, Rody A, Holtrich U, Pusztai L, Ruckhaeberle E, Liedtke C, Ahr A, Heinrich TM, Sänger N, Becker S, Karn T. Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes. Breast Cancer Research And Treatment 2012, 137: 407-416. PMID: 23242614, DOI: 10.1007/s10549-012-2356-2.Peer-Reviewed Original ResearchMeSH KeywordsB-LymphocytesBreast NeoplasmsDisease-Free SurvivalFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticHumansInterleukin-8Middle AgedOligonucleotide Array Sequence AnalysisPredictive Value of TestsPrognosisProportional Hazards ModelsReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsTriple-negative breast cancerCell/ILNegative breast cancerBreast cancer subtypesPrognostic valueBreast cancerBetter prognosisB cellsCancer subtypesIntrinsic breast cancer subtypesPrimary breast cancer samplesER-negative subtypesEvent-free survivalB cell signaturesHigher B cellsSignificant prognostic valueTriple-negative samplesBreast cancer samplesRoutine clinicopathological variablesOnly significant predictorSubtype-specific analysesTNBC subtypesClinicopathological variablesOutcome predictorsPrognostic evaluationDistinct tumor protein p53 mutants in breast cancer subgroups
Dumay A, Feugeas J, Wittmer E, Lehmann‐Che J, Bertheau P, Espié M, Plassa L, Cottu P, Marty M, André F, Sotiriou C, Pusztai L, de Thé H. Distinct tumor protein p53 mutants in breast cancer subgroups. International Journal Of Cancer 2012, 132: 1227-1231. PMID: 22886769, DOI: 10.1002/ijc.27767.Peer-Reviewed Original ResearchConceptsBasal tumorsLuminal tumorsMolecular apocrine tumoursDifferent breast cancer subtypesBreast cancer subgroupsBreast cancer subtypesP53 mutation statusApocrine tumorsTumor protein p53Molecular apocrineCancer subgroupsBreast cancerTP53 alterationsMutation statusBreast tumorsLoss of functionCancer subtypesTumorsComplex mutationsP53 gainHigh frequencyHigh rateDifferent functional consequencesMissense mutationsProtein p53Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers
Santarpia L, Qi Y, Stemke-Hale K, Wang B, Young EJ, Booser DJ, Holmes FA, O’Shaughnessy J, Hellerstedt B, Pippen J, Vidaurre T, Gomez H, Valero V, Hortobagyi GN, Symmans WF, Bottai G, Di Leo A, Gonzalez-Angulo AM, Pusztai L. Mutation profiling identifies numerous rare drug targets and distinct mutation patterns in different clinical subtypes of breast cancers. Breast Cancer Research And Treatment 2012, 134: 333-343. PMID: 22538770, PMCID: PMC3885980, DOI: 10.1007/s10549-012-2035-3.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast cancer subtypesBreast cancerPIK3CA mutationsCancer subtypesEstrogen receptor-positive cancersBreast cancer molecular subtypesMajor breast cancer subtypesSingle needle biopsyProspective clinical trialsReceptor-positive cancersDifferent breast cancer subtypesDifferent clinical subtypesNegative breast cancerCancer molecular subtypesFine-needle aspirationMutation patternsClinical subtypesClinical trialsNeedle biopsyMolecular subtypesNeedle aspirationInvestigational drugsStage IFBXW7 mutations
2011
Relationship between differences in RNA or protein expression and the effects of race/ethnicity on breast cancer outcomes.
Chavez-MacGregor M, Liu S, Chen H, Do K, Pusztai L, Symmans W, Hortobagyi G, Mills G, Meric-Bernstam F, Gonzalez-Angulo A. Relationship between differences in RNA or protein expression and the effects of race/ethnicity on breast cancer outcomes. Journal Of Clinical Oncology 2011, 29: 157-157. DOI: 10.1200/jco.2011.29.27_suppl.157.Peer-Reviewed Original Research
2008
Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer
Wolff AC, Berry D, Carey LA, Colleoni M, Dowsett M, Ellis M, Garber JE, Mankoff D, Paik S, Pusztai L, Smith ML, Zujewski J. Research Issues Affecting Preoperative Systemic Therapy for Operable Breast Cancer. Journal Of Clinical Oncology 2008, 26: 806-813. PMID: 18258990, DOI: 10.1200/jco.2007.15.2983.Peer-Reviewed Original ResearchMeSH KeywordsAngiogenesis InhibitorsAntineoplastic AgentsApoptosisBiomarkersBiomedical ResearchBreast NeoplasmsCell ProliferationEpidemiologic Research DesignErbB ReceptorsEthics, ClinicalFemaleGene Expression ProfilingHumansMastectomy, SegmentalNeoadjuvant TherapyPatient AdvocacyPreoperative CarePrognosisReceptors, SteroidTreatment OutcomeConceptsPreoperative systemic therapyOperable breast cancerSystemic therapyBreast cancerTrial designEnd pointCohesive multidisciplinary teamBreast conservation ratesEffective alternative therapyTrial end pointsLong-term outcomesSpecific breast cancer subtypesPredictors of responseNovel trial designsIntermediate end pointsBreast cancer subtypesIndividual patient subgroupsAdjuvant trialsPatient subgroupsSmall trialsAlternative therapiesMAIN OUTCOMEClinical careCancer subtypesMultidisciplinary team