2023
Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Rediti M, Fernandez-Martinez A, Venet D, Rothé F, Hoadley K, Parker J, Singh B, Campbell J, Ballman K, Hillman D, Winer E, El-Abed S, Piccart M, Di Cosimo S, Symmans W, Krop I, Salgado R, Loi S, Pusztai L, Perou C, Carey L, Sotiriou C. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials. Nature Communications 2023, 14: 7053. PMID: 37923752, PMCID: PMC10624889, DOI: 10.1038/s41467-023-42635-2.Peer-Reviewed Original ResearchConceptsEvent-free survivalHER2-positive breast cancerPathological complete responseCALGB 40601Breast cancerBreast pathological complete responseStromal tumor-infiltrating lymphocytesHormone receptor statusPhase III trialsClinical nodal statusIndependent prognostic factorTumor-infiltrating lymphocytesIdentification of patientsBreast cancer prognosisT cell receptorNeoadjuvant paclitaxelNeoadjuvant therapyIII trialsNodal statusComplete responsePrognostic factorsPrognostic scoreReceptor statusClinicopathological featuresResidual disease
2021
Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMACopy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial.
Venet D, Rediti M, Maetens M, Fumagalli D, Brown DN, Majjaj S, Salgado R, Pusztai L, Harbeck N, El-Abed S, Wang Y, Saura C, Gomez H, Semiglazov VF, de Azambuja E, Huober J, Nuciforo P, Di Cosimo S, Piccart M, Loi S, Rothé F, Sotiriou C. Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial. Clinical Cancer Research 2021, 27: clincanres.1317.2021. PMID: 34321278, DOI: 10.1158/1078-0432.ccr-21-1317.Peer-Reviewed Original ResearchConceptsPathologic complete responseNeoALTTO trialCopy number aberrationsBreast cancerHER2-positive early-stage breast cancerEstrogen receptor-positive subgroupNeoadjuvant anti-HER2 therapyEarly-stage breast cancerHER2-positive breast cancerPhase III clinical trialsAnti-HER2 therapyAnti-HER2 agentsPredictors of responseReceptor-positive subgroupNumber aberration analysisCopy number levelsWarrants further investigationHeterogeneity of responseComplete responseSurvival outcomesWhole cohortClinical trialsImmune processesPatientsSignificant association
2020
Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer
Kunst N, Wang SY, Hood A, Mougalian SS, DiGiovanna MP, Adelson K, Pusztai L. Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer. JAMA Network Open 2020, 3: e2027074. PMID: 33226431, PMCID: PMC7684449, DOI: 10.1001/jamanetworkopen.2020.27074.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicBreast NeoplasmsCase-Control StudiesCost-Benefit AnalysisCross-Linking ReagentsDrug Therapy, CombinationFemaleHumansImmunosuppressive AgentsMiddle AgedNeoadjuvant TherapyPaclitaxelQuality-Adjusted Life YearsReceptor, ErbB-2TrastuzumabTubulin ModulatorsUnited StatesConceptsErbB2-positive breast cancerAdjuvant treatment strategiesAdjuvant T-DM1Pathologic complete responseT-DM1Treatment strategiesBreast cancerKATHERINE trialResidual diseaseNeoadjuvant regimenHigher health benefitsHealth care payer perspectiveAdjuvant trastuzumab emtansineAnthracycline/cyclophosphamideDifferent adjuvant therapiesFlatiron Health databaseIncremental cost-effectiveness ratioNeoadjuvant treatment optionsHealth benefitsPositive breast cancerCare payer perspectiveCost-effectiveness ratioBase-case analysisDecision analytic modelH. PatientsAssociation of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer
Consortium I, Yee D, DeMichele A, Yau C, Isaacs C, Symmans W, Albain K, Chen Y, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal I, Tawfik O, LeBeau L, Sahoo S, Vinh T, Chien A, Forero-Torres A, Stringer-Reasor E, Wallace A, Pusztai L, Boughey J, Ellis E, Elias A, Lu J, Lang J, Han H, Clark A, Nanda R, Northfelt D, Khan Q, Viscusi R, Euhus D, Edmiston K, Chui S, Kemmer K, Park J, Liu M, Olopade O, Leyland-Jones B, Tripathy D, Moulder S, Rugo H, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton N, Veer L, Perlmutter J, Melisko M, Wilson A, Peterson G, Asare A, Buxton M, Paoloni M, Clennell J, Hirst G, Singhrao R, Steeg K, Matthews J, Asare S, Sanil A, Berry S, Esserman L, Berry D. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer. JAMA Oncology 2020, 6: 1355-1362. PMID: 32701140, PMCID: PMC7378873, DOI: 10.1001/jamaoncol.2020.2535.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalProgression-Free SurvivalProportional Hazards ModelsReceptor, ErbB-2TaxoidsTrastuzumabTreatment OutcomeConceptsDistant recurrence-free survivalPathologic complete responseEvent-free survivalI-SPY2 trialRecurrence-free survivalLong-term outcomesBreast cancerComplete responseNeoadjuvant therapyPlatform trialsMolecular subtypesHigh-risk operable breast cancerThree-year event-free survivalHormone receptorsClinical stage 2Phase 3 confirmatory trialOperable breast cancerSubpopulation of womenNovel therapeutic combinationsStage 2Investigational regimensNeoadjuvant treatmentPrior surgeryTaxane treatmentStandard therapyEarly Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy
Di Cosimo S, Appierto V, Pizzamiglio S, Silvestri M, Baselga J, Piccart M, Huober J, Izquierdo M, de la Pena L, Hilbers FS, de Azambuja E, Untch M, Pusztai L, Pritchard K, Nuciforo P, Vincent-Salomon A, Symmans F, Apolone G, de Braud FG, Iorio MV, Verderio P, Daidone MG. Early Modulation of Circulating MicroRNAs Levels in HER2-Positive Breast Cancer Patients Treated with Trastuzumab-Based Neoadjuvant Therapy. International Journal Of Molecular Sciences 2020, 21: 1386. PMID: 32085669, PMCID: PMC7073028, DOI: 10.3390/ijms21041386.Peer-Reviewed Original ResearchConceptsPathological complete responseNeoadjuvant therapyHER2-positive breast cancer patientsTrastuzumab-based neoadjuvant therapyAvailable predictive biomarkersBreast cancer patientsEstrogen receptor statusComplete responseReceptor statusCancer patientsPredictive biomarkersTreatment responseHCC progressionPatientsPredictive valueBivariate analysisMean differencePlasma pairsTherapyEarly modulationMicroRNA levelsTrastuzumabMAPK signalingMetabolism regulationKEGG analysis
2019
Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy
Abu-Khalaf MM, Safonov A, Stratton J, Wang S, Hatzis C, Park E, Pusztai L, Gross CP, Russell R. Examining the cost-effectiveness of baseline left ventricular function assessment among breast cancer patients undergoing anthracycline-based therapy. Breast Cancer Research And Treatment 2019, 176: 261-270. PMID: 31020471, DOI: 10.1007/s10549-019-05178-z.Peer-Reviewed Original ResearchConceptsIncremental cost-effectiveness ratioEquilibrium radionuclide angiographyCardiac risk factorsBreast cancer patientsVentricular function assessmentRisk factorsAbnormal LVEFBaseline LVEFCancer patientsBreast cancerFunction assessmentPotential cardiac risk factorsSelf-reported risk factorsAnthracycline-based therapyLeft ventricular function assessmentCoronary artery diseaseCost-effectiveness ratioArtery diseaseTrastuzumab therapyCardiac screeningPatient populationRadionuclide angiographyCardiotoxicity riskPayer perspectiveRetrospective analysis
2018
Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2018, 4: e181564-e181564. PMID: 29902299, PMCID: PMC6224305, DOI: 10.1001/jamaoncol.2018.1564.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsFemaleHumansLapatinibMiddle AgedReceptor, ErbB-2Receptors, Antigen, T-CellTrastuzumabConceptsDual HER2 blockadeImmune gene signaturesPathologic complete responseDual HER2HER2 blockadeNeoALTTO trialDual anti-HER2 blockadeHigher immune gene expressionTrastuzumab Treatment Optimisation (ALTTO) trialHER2-positive breast cancerGene signatureAnti-HER2 blockadeHigher useHER2-positive patientsMultivariable logistic regressionRandomized clinical trialsGood responseHigh rateImmune gene expressionNeoadjuvant lapatinibTherapy armIdentifies patientsNeoadjuvant therapyComplete responseGene expression signaturesComparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies
Wei W, Kurita T, Hess KR, Sanft T, Szekely B, Hatzis C, Pusztai L. Comparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies. JAMA Oncology 2018, 4: e175092-e175092. PMID: 29372234, PMCID: PMC5885272, DOI: 10.1001/jamaoncol.2017.5092.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantEligibility DeterminationFemaleHumansLymph NodesLymphatic MetastasisMiddle AgedNeoplasm Recurrence, LocalNeoplasm, ResidualPatient SelectionPrognosisRandomized Controlled Trials as TopicReproducibility of ResultsResearch DesignRetrospective StudiesRisk FactorsSurvival AnalysisTrastuzumabTumor BurdenWatchful WaitingYoung AdultConceptsTumor sizeAdjuvant trialsEligibility criteriaNodal statusClinical trialsResidual riskEarly-stage breast cancerAdjuvant clinical trialsBaseline prognostic riskFuture adjuvant trialsResidual risk estimatesRisk of recurrenceBreast cancer therapyRisk thresholdTrial powerClinical trial powerTrial eligibilityAdjuvant therapyCare therapyConsecutive patientsPrognostic riskPatient eligibilityTrial populationPatient cohortControl armSingle-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Burrello T, Abu-Khalaf M, Sabbath K, Sanft T, Brandt DS, Hofstatter EW, Hatzis C, DiGiovanna MP, Pusztai L. Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer. Breast Cancer Research And Treatment 2018, 169: 333-340. PMID: 29396664, DOI: 10.1007/s10549-017-4653-2.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerPhase II trialII trialNeoadjuvant chemotherapyPCR rateHormone receptorsBreast cancerGrade 3/4 adverse eventsPathologic complete response rateCyclophosphamide neoadjuvant chemotherapyComplete response rateSymptomatic heart failureAsymptomatic decreaseNeoadjuvant settingWeekly paclitaxelAdverse eventsHeart failureTherapeutic plateauCardiac functionInterim analysisStage IResponse ratePurposeThe purposePatientsNegative cases
2017
Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06)
Ponde N, Bradbury I, Lambertini M, Ewer M, Campbell C, Ameels H, Zardavas D, Di Cosimo S, Baselga J, Huober J, Izquierdo M, Fumagalli D, Bozovic-Spasojevic I, Maetens M, Harbeck N, Pusztai L, Berghorn M, Im YH, Borrego MR, Chen DR, Rodeheffer R, Piccart M, Suter T, de Azambuja E. Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1-06). Breast Cancer Research And Treatment 2017, 168: 631-638. PMID: 29280043, PMCID: PMC5843537, DOI: 10.1007/s10549-017-4628-3.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyNT-proBNPBiomarker elevationCardiac toxicityEarly predictorHER2-positive early-stage breast cancerEarly-stage breast cancerAnthracycline-naïve patientsEarly cardiac toxicityLevels of TnTNT-proBNP elevationBrain natriuretic peptideBreast cancer patientsNeoALTTO trialWeekly paclitaxelCardiac dysfunctionTreatment armsCardiac damageNatriuretic peptideCancer patientsCardiac biomarkersBreast cancerPatientsTroponin TAmino-terminal fragmentLong-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. Journal Of Clinical Oncology 2017, 35: jco.2015.63.101. PMID: 28135148, PMCID: PMC5455352, DOI: 10.1200/jco.2015.63.1010.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelPhenotypePrognosisProspective StudiesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk AssessmentSurvival RateTime FactorsTrastuzumabTumor BurdenConceptsResidual cancer burdenPhenotypic subsetsNeoadjuvant chemotherapyValidation cohortPrognostic riskCancer burdenRCB classBreast cancerRCB indexRelapse-free survival estimatesRelapse-free survival rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Hormone receptorsOriginal development cohortGrowth factor receptor 2Clinical-pathologic variablesKaplan-Meier analysisLong-term prognosisLog-rank testIndependent validation cohortBreast cancer subtypesLong-term survivalFactor receptor 2Concurrent trastuzumabPathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial
Shi W, Jiang T, Nuciforo P, Hatzis C, Holmes E, Harbeck N, Sotiriou C, Peña L, Loi S, Rosa DD, Chia S, Wardley A, Ueno T, Rossari J, Eidtmann H, Armour A, Piccart-Gebhart M, Rimm DL, Baselga J, Pusztai L. Pathway level alterations rather than mutations in single genes predict response to HER2-targeted therapies in the neo-ALTTO trial. Annals Of Oncology 2017, 28: 128-135. PMID: 28177460, PMCID: PMC5834036, DOI: 10.1093/annonc/mdw434.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiopsy, Fine-NeedleBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA, NeoplasmExome SequencingFemaleHumansLapatinibMolecular Targeted TherapyMutationProportional Hazards ModelsProtein Kinase InhibitorsQuinazolinesReceptor, ErbB-2RhoA GTP-Binding ProteinTrastuzumabConceptsPathologic complete response
2016
T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
Dzimitrowicz H, Berger M, Vargo C, Hood A, Abdelghany O, Raghavendra AS, Tripathy D, Valero V, Hatzis C, Pusztai L, Murthy R. T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab. Journal Of Clinical Oncology 2016, 34: 3511-3517. PMID: 27298406, PMCID: PMC6075965, DOI: 10.1200/jco.2016.67.3624.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsDisease ProgressionHumansMaytansineMiddle AgedNeoplasm MetastasisReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsRetreatmentRetrospective StudiesTrastuzumabConceptsMetastatic breast cancerHER2-positive metastatic breast cancerTumor response rateT-DM1Prior pertuzumabCancer HospitalBreast cancerMetastatic human epidermal growth factor receptorResponse rateStandard first-line therapyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2MD Anderson Cancer CenterHuman epidermal growth factor receptorFourth-line treatmentSmilow Cancer HospitalT-DM1 activityFirst-line therapyThird of patientsGrowth factor receptor 2Contemporary patient populationJames Cancer HospitalResults of patientsAdo-trastuzumab emtansineElectronic pharmacy recordsAdaptive Randomization of Neratinib in Early Breast Cancer
Park JW, Liu MC, Yee D, Yau C, van 't Veer LJ, Symmans WF, Paoloni M, Perlmutter J, Hylton NM, Hogarth M, DeMichele A, Buxton MB, Chien AJ, Wallace AM, Boughey JC, Haddad TC, Chui SY, Kemmer KA, Kaplan HG, Isaacs C, Nanda R, Tripathy D, Albain KS, Edmiston KK, Elias AD, Northfelt DW, Pusztai L, Moulder SL, Lang JE, Viscusi RK, Euhus DM, Haley BB, Khan QJ, Wood WC, Melisko M, Schwab R, Helsten T, Lyandres J, Davis SE, Hirst GL, Sanil A, Esserman LJ, Berry DA. Adaptive Randomization of Neratinib in Early Breast Cancer. New England Journal Of Medicine 2016, 375: 11-22. PMID: 27406346, PMCID: PMC5259558, DOI: 10.1056/nejmoa1513750.Peer-Reviewed Original ResearchConceptsPathological complete responseComplete responseBreast cancerNeoadjuvant therapyStandard chemotherapyHuman epidermal growth factor receptor 2 (HER2) statusEpidermal growth factor receptor 2 statusBiomarker signaturesSerial magnetic resonance imagingI-SPY 2 TRIALTyrosine kinase inhibitor neratinibClinical stage IIPrimary end pointHormone receptor statusPhase 2 trialPhase 3 trialStandard neoadjuvant chemotherapyEarly breast cancerMultiple new agentsAdaptive randomizationNegative breast cancerConfirmatory phase 3 trialPhase 3 testingExperimental groupMagnetic resonance imaging
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 ResearchMeasurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer
Carvajal-Hausdorf DE, Schalper KA, Pusztai L, Psyrri A, Kalogeras KT, Kotoula V, Fountzilas G, Rimm DL. Measurement of Domain-Specific HER2 (ERBB2) Expression May Classify Benefit From Trastuzumab in Breast Cancer. Journal Of The National Cancer Institute 2015, 107: djv136. PMID: 25991002, PMCID: PMC4554192, DOI: 10.1093/jnci/djv136.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantClinical Trials as TopicDisease-Free SurvivalExtracellular SpaceFemaleFluorescent Antibody TechniqueGene Expression Regulation, NeoplasticHumansIntracellular SpaceKaplan-Meier EstimateMiddle AgedPredictive Value of TestsPrognosisReceptor, ErbB-2Sensitivity and SpecificityTissue Array AnalysisTrastuzumabTreatment OutcomeConceptsHuman epidermal growth factor receptor 2ECD expressionICD statusLonger DFSQuantitative immunofluorescenceTrastuzumab therapyPrognostic valueBreast cancerTissue microarrayEpidermal growth factor receptor 2Adjuvant trastuzumab therapyDisease-free survival analysisTrastuzumab-treated patientsGrowth factor receptor 2High positive predictive valueHER2-positive tumorsKaplan-Meier estimatesFactor receptor 2ERBB2 gene amplificationHER2 protein expressionPositive predictive valueExtracellular domainAdjuvant chemotherapyHER2-ICDBetter DFSHigh HER2 Expression Correlates with Response to the Combination of Lapatinib and Trastuzumab
Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, Chenna A, Winslow J, Serra V, Parra JL, Prudkin L, Jimenez J, Aura C, Harbeck N, Pusztai L, Ellis C, Eidtmann H, Arribas J, Cortes J, de Azambuja E, Piccart M, Baselga J. High HER2 Expression Correlates with Response to the Combination of Lapatinib and Trastuzumab. Clinical Cancer Research 2015, 21: 569-576. PMID: 25467182, DOI: 10.1158/1078-0432.ccr-14-1824.Peer-Reviewed Original ResearchConceptsProgression-free survivalPathologic complete responseAnti-HER2 therapyHER2 expressionBreast cancerLonger progression-free survivalCombination of lapatinibExpression of p95HER2Trastuzumab-based therapyHigh HER2 expressionMetastatic breast cancerHER2 protein expressionComplete responseHR statusClinical benefitPrimary tumorHER2 levelsCox modelP95HER2PatientsPositive subsetTrastuzumabLapatinibHER2Expression correlates
2012
Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer
Liu JC, Voisin V, Bader GD, Deng T, Pusztai L, Symmans WF, Esteva FJ, Egan SE, Zacksenhaus E. Seventeen-gene signature from enriched Her2/Neu mammary tumor-initiating cells predicts clinical outcome for human HER2+:ERα− breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 5832-5837. PMID: 22460789, PMCID: PMC3326451, DOI: 10.1073/pnas.1201105109.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsCalcium-Binding ProteinsCD24 AntigenCell DifferentiationCell DivisionEstrogen Receptor alphaFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansIntercellular Signaling Peptides and ProteinsJagged-1 ProteinMembrane ProteinsMiceNeoadjuvant TherapyNeoplastic Stem CellsPrognosisReceptor, ErbB-2Serrate-Jagged ProteinsSignal TransductionTrastuzumabTreatment OutcomeConceptsTumor-initiating cellsMammary tumor-initiating cellsBreast cancerClinical outcomesPrognostic signatureHuman epidermal growth factor receptorAnti-HER2 drugsAnti-HER2 therapyHigh-risk patientsHigh-risk subgroupsEpidermal growth factor receptorGrowth factor receptorBC cohortRisk patientsAggressive diseaseBC patientsRetrospective analysisImmune responsePrognostic powerTumor growthPatientsChemotherapyFactor receptorCancerFraction of cellsLapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial
Baselga J, Bradbury I, Eidtmann H, Di Cosimo S, de Azambuja E, Aura C, Gómez H, Dinh P, Fauria K, Van Dooren V, Aktan G, Goldhirsch A, Chang TW, Horváth Z, Coccia-Portugal M, Domont J, Tseng LM, Kunz G, Sohn JH, Semiglazov V, Lerzo G, Palacova M, Probachai V, Pusztai L, Untch M, Gelber RD, Piccart-Gebhart M, Team O. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. The Lancet 2012, 379: 633-640. PMID: 22257673, PMCID: PMC5705192, DOI: 10.1016/s0140-6736(11)61847-3.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDiarrheaDrug Administration ScheduleFemaleHumansInfusions, IntravenousLapatinibLiverMiddle AgedNeoadjuvant TherapyPaclitaxelQuinazolinesReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsPathological complete responseBreast cancerHER2-positive early breast cancerHER2-positive primary breast cancerAnti-HER2 monoclonal antibody trastuzumabHER2-positive breast cancerHER2-overexpressing breast cancerTyrosine kinase inhibitor lapatinibGrade 3 diarrheaLiver enzyme alterationsAnti-HER2 agentsAnti-HER2 therapyPhase 3 studyPhase 3 trialEarly breast cancerPrimary breast cancerSingle-agent therapySynergistic antitumour activityMajor cardiac dysfunctionKinase inhibitor lapatinibMonoclonal antibody trastuzumabAdjuvant chemotherapyNeoadjuvant phaseNeoadjuvant settingOral lapatinib