2024
A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Giordano A, Kumthekar P, Jin Q, Kurt B, Ren S, Li T, Leone J, Mittendorf E, Pereslete A, Sharp L, Davis R, DiLullo M, Tayob N, Mayer E, Winer E, Tolaney S, Lin N. A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39226397, PMCID: PMC11528201, DOI: 10.1158/1078-0432.ccr-24-1161.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesClinical benefit rateCancer brain metastasesCentral nervous systemCNS responseBrain metastasesOverall response rateOverall survivalAny-grade adverse eventsEffective systemic therapy optionsNeuro-Oncology Brain MetastasesHER2-positive breast cancerIntracranial partial responseSystemic therapy optionsPhase II studyPhase II trialCNS ORRRANO-BMDose delaysPartial responseII studyPrimary endpointHigh-doseBenefit rateRNA-Seq based gene expression profiling of baseline and on-treatment breast tumors to predict response to HER2-directed therapy, without chemotherapy (TBCRC026).
Hennessy M, Fernández A, Huang C, Cimino-Mathews A, Denbow R, Abramson V, Rimawi M, Specht J, Storniolo A, Valero V, Vaklavas C, Winer E, Krop I, Wolff A, Wahl R, Thompson E, Stearns V, Perou C, Carey L, Connolly R. RNA-Seq based gene expression profiling of baseline and on-treatment breast tumors to predict response to HER2-directed therapy, without chemotherapy (TBCRC026). Journal Of Clinical Oncology 2024, 42: 530-530. DOI: 10.1200/jco.2024.42.16_suppl.530.Peer-Reviewed Original ResearchRelapse-free survivalB cell signaturesGene expression signaturesHER2-directed therapyPET/CT parametersER-negativeHER2 subtypeClinical outcomesEarly stage HER2-positive breast cancerResponse to HER2-directed therapyAssociated with lack of responseHER2-positive breast cancerGene expression changesUnivariate logistic regression analysisHER2-positive cohortIncreased immune signalingMetabolic changesAssociated with pCRNatural killer cellsNested Cox modelsLogistic regression analysisWilcoxon signed-rank testHER2 ampliconFDG-PET/CTHER2- tumorsHER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial
Li Z, Filho O, Viale G, dell'Orto P, Russo L, Goyette M, Kamat A, Yardley D, Abramson V, Arteaga C, Spring L, Chiotti K, Halsey C, Waks A, King T, Lester S, Bellon J, Winer E, Spellman P, Krop I, Polyak K. HER2 heterogeneity and treatment response-associated profiles in HER2-positive breast cancer in the NCT02326974 clinical trial. Journal Of Clinical Investigation 2024, 134: e176454. PMID: 38300710, PMCID: PMC10977978, DOI: 10.1172/jci176454.Peer-Reviewed Original ResearchPathological complete responseHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-targeted therapyPre-treatment tumorsErbB signalingHER2-targeted antibodiesBasal-like featuresHER2 protein levelsStratification of patientsNational Cancer InstituteNeoadjuvant trialsComplete responseResidual tumorT-DM1Copy number heterogeneityTrastuzumab emtansineERBB2 mRNAImmune infiltrationDownstream pathway componentsClinical challengeClinical trialsTumor
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 diseaseCorrelation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial)
Hennessy M, Leal J, Huang C, Solnes L, Denbow R, Abramson V, Carey L, Liu M, Rimawi M, Specht J, Storniolo A, Valero V, Vaklavas C, Winer E, Krop I, Wolff A, Cimino-Mathews A, Wahl R, Stearns V, Connolly R. Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial). Journal Of Nuclear Medicine 2023, 64: jnumed.123.265853. PMID: 37652539, DOI: 10.2967/jnumed.123.265853.Peer-Reviewed Original ResearchConceptsF-FDG PET/CTHER2-positive breast cancerRecurrence-free survivalPET/CTPathologic complete responseOverall survivalBreast cancerOperable HER2-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Growth factor receptor 2Kaplan-Meier methodStatistical significanceLean body massFactor receptor 2Imaging-based biomarkersCorrelation of SUVHER2 therapyNeoadjuvant trastuzumabNeoadjuvant therapyAdjuvant therapyComplete responsePhysician's discretionOS outcomesCox regressionNodal positivity and systemic therapy among patients with clinical T1–T2N0 human epidermal growth factor receptor‐positive breast cancer: Results from two international cohorts
Weiss A, Martínez‐Sáez O, Waks A, Laws A, McGrath M, Tarantino P, Portnow L, Winer E, Rey M, Tapia M, Prat A, Partridge A, Tolaney S, Cejalvo J, Mittendorf E, King T. Nodal positivity and systemic therapy among patients with clinical T1–T2N0 human epidermal growth factor receptor‐positive breast cancer: Results from two international cohorts. Cancer 2023, 129: 1836-1845. PMID: 36951169, DOI: 10.1002/cncr.34750.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerNeoadjuvant chemotherapyUpfront surgeryNodal positivityBreast cancerTumor sizeALND ratesCT1c tumorsTreatment strategiesSmall human epidermal growth factor receptor 2Lymph node dissection ratesReceptor-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical T1-T2Lymph node positiveHER2-positive patientsGrowth factor receptor 2Optimal treatment strategyFactor receptor 2Nodal statusSystemic therapyNode positiveAxillary imagingPositive tumorsAdjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial
Tolaney S, Tarantino P, Graham N, Tayob N, Parè L, Villacampa G, Dang C, Yardley D, Moy B, Marcom P, Albain K, Rugo H, Ellis M, Shapira I, Wolff A, Carey L, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo J, Weiss J, Wagle N, Partridge A, Waks A, Hudis C, Krop I, Burstein H, Prat A, Winer E. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. The Lancet Oncology 2023, 24: 273-285. PMID: 36858723, DOI: 10.1016/s1470-2045(23)00051-7.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerInvasive disease-free survivalDisease-free survivalRecurrence-free intervalAdjuvant paclitaxelBreast cancerEastern Cooperative Oncology Group performance statusInvasive disease-free survival eventsDisease-free survival eventsHormone receptor-positive diseaseNew contralateral breast cancerBreast cancer-specific survivalProtocol-defined treatmentCancer-specific survivalReceptor-positive diseasePhase 2 studyContralateral breast cancerLong-term outcomesAPT trialCause deathEligible patientsIntravenous paclitaxelTrastuzumab weeklyDistant recurrenceIpsilateral recurrence
2022
Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT)
Sella T, Zheng Y, Tayob N, Ruddy K, Freedman R, Dang C, Yardley D, Isakoff S, Valero V, DeMeo M, Burstein H, Winer E, Wolff A, Krop I, Partridge A, Tolaney S. Treatment discontinuation, patient-reported toxicities and quality-of-life by age following trastuzumab emtansine or paclitaxel/trastuzumab (ATEMPT). Npj Breast Cancer 2022, 8: 127. PMID: 36450763, PMCID: PMC9712612, DOI: 10.1038/s41523-022-00495-x.Peer-Reviewed Original ResearchHER2-positive breast cancerPatient-reported toxicityPatient-reported outcomesT-DM1Treatment discontinuationTrastuzumab emtansineBreast cancerStage I HER2-positive breast cancerAdjuvant trastuzumab emtansineExcellent disease outcomesLess activity impairmentPaclitaxel/trastuzumabSocial/familyPositive breast cancerSuperior QoLOlder patientsTreatment toleranceTreatment armsTreatment regimensEligible participantsGlobal QoLTherapy optionsActivity impairmentMultivariable modelDisease outcomePhase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer
Waks AG, Keenan TE, Li T, Tayob N, Wulf GM, Richardson ET, Attaya V, Anderson L, Mittendorf EA, Overmoyer B, Winer EP, Krop IE, Agudo J, Van Allen EM, Tolaney SM. Phase Ib study of pembrolizumab in combination with trastuzumab emtansine for metastatic HER2-positive breast cancer. Journal For ImmunoTherapy Of Cancer 2022, 10: e005119. PMID: 36252998, PMCID: PMC9577940, DOI: 10.1136/jitc-2022-005119.Peer-Reviewed Original ResearchConceptsObjective response rateProgression-free survivalMetastatic breast cancerAdverse eventsBreast cancerT-DM1Immune biomarkersTrastuzumab emtansineHER2-positive metastatic breast cancerMetastatic HER2-positive breast cancerGrade 3 adverse eventsMedian progression-free survivalTreatment-related adverse eventsHuman epidermal growth factor receptor 2Cell death ligand 1HER2-positive breast cancerEpidermal growth factor receptor 2Dose-finding cohortPhase 2 dosePhase Ib studyPhase Ib trialAnti-HER2 therapyDose-limiting toxicityGrowth factor receptor 2Immune checkpoint blockadePreclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases
Kabraji S, Ni J, Sammons S, Li T, Van Swearingen AED, Wang Y, Pereslete A, Hsu L, DiPiro PJ, Lascola C, Moore H, Hughes M, Raghavendra AS, Gule-Monroe M, Murthy RK, Winer EP, Anders CK, Zhao JJ, Lin NU. Preclinical and clinical efficacy of trastuzumab deruxtecan in breast cancer brain metastases. Clinical Cancer Research 2022, 29: 174-182. PMID: 36074155, PMCID: PMC9811155, DOI: 10.1158/1078-0432.ccr-22-1138.Peer-Reviewed Original ResearchConceptsBreast cancer brain metastasesActive brain metastasesObjective response rateCNS objective response rateCancer brain metastasesBrain metastasesT-DXdPatient-derived xenograftsPDX modelsCohort studyTrastuzumab deruxtecanClinical efficacyClinical trialsHER2-positive breast cancer brain metastasesMetastatic HER2-positive breast cancerResponse rateMulti-institutional cohort studyHER2-positive breast cancerRetrospective multi-institutional cohort studyOrthotopic patient-derived xenograftsRetrospective cohort studyProspective clinical trialsSubset of patientsCentral nervous system activityPivotal clinical trials191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026)
Hennessy M, Leal J, Huang C, Solnes L, Denbow R, Abramson V, Carey L, Liu M, Rimawi M, Specht J, Storniolo A, Valero V, Vaklavas C, Winer E, Krop I, Wolff A, Cimino-Mathews A, Wahl R, Stearns V, Connolly R. 191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026). Annals Of Oncology 2022, 33: s623-s624. DOI: 10.1016/j.annonc.2022.07.226.Peer-Reviewed Original ResearchA prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer
Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O, Alberti J, Deane J, Rosenberg SM, Frank E, Tolaney SM, Krop IE, Tung NM, Tayob N, King TA, Mittendorf EA, Winer EP. A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. Npj Breast Cancer 2022, 8: 63. PMID: 35538105, PMCID: PMC9091255, DOI: 10.1038/s41523-022-00429-7.Peer-Reviewed Original ResearchPathologic complete responseProspective trialBreast cancerSingle-arm prospective trialHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant treatment plansDose of THPEarly-stage HER2Incomplete clinical responsePrimary feasibility endpointTrastuzumab/pertuzumabMajority of patientsOngoing prospective trialsStage II tumorsLong-term efficacyBreast cancer recurrenceEpidermal growth factor receptorAdjuvant chemotherapyFeasibility endpointsGrowth factor receptorNeoadjuvant regimenAdjuvant therapyDoublet therapyPrimary endpointp16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases
Ni J, Kabraji S, Xie S, Wang Y, Pan P, He X, Liu Z, Leone JP, Long HW, Brown MA, Winer EP, Dillon DAR, Lin NU, Zhao JJ. p16INK4A-deficiency predicts response to combined HER2 and CDK4/6 inhibition in HER2+ breast cancer brain metastases. Nature Communications 2022, 13: 1473. PMID: 35304445, PMCID: PMC8933392, DOI: 10.1038/s41467-022-29081-2.Peer-Reviewed Original ResearchConceptsPatient-derived xenograftsBrain metastasesMetastatic HER2-positive breast cancerBiomarker-driven clinical trialsBreast cancer brain metastasesHER2-positive breast cancerOrthotopic patient-derived xenograftsMajority of HER2Cancer brain metastasesCDK4/6 inhibitionProtein immunohistochemistryClinical trialsBreast cancerHER2Tumor suppressor p16INK4aPatientsMetastasisBCBMAbemaciclibTucatinibXenograftsImmunohistochemistryCancerCDK4/6TrialsCardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial
Barroso-Sousa R, Tarantino P, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy KJ, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I, Tolaney SM. Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial. Npj Breast Cancer 2022, 8: 18. PMID: 35173164, PMCID: PMC8850608, DOI: 10.1038/s41523-022-00385-2.Peer-Reviewed Original ResearchLeft ventricular ejection fractionHER2-positive breast cancerAdjuvant T-DM1Adjuvant trastuzumab emtansineT-DM1Adverse eventsCardiac outcomesTrastuzumab emtansineBreast cancerStage I HER2-positive breast cancerAsymptomatic left ventricular ejection fractionBaseline left ventricular ejection fractionAnthracycline-free regimensAsymptomatic LVEF declineResidual invasive diseaseT-DM1 armCardiac adverse eventsVentricular systolic dysfunctionSignificant adverse eventsVentricular ejection fractionBody mass indexFavorable toxicity profilePotential therapeutic optionBreast Cancer StudyAdjuvant paclitaxelLocal Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer
Bellon JR, Tayob N, Yang DD, Tralins J, Dang CT, Isakoff SJ, DeMeo M, Burstein HJ, Partridge AH, Winer EP, Krop IE, Tolaney SM. Local Therapy Outcomes and Toxicity From the ATEMPT Trial (TBCRC 033): A Phase II Randomized Trial of Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab in Women With Stage I HER2-Positive Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2022, 113: 117-124. PMID: 34990776, DOI: 10.1016/j.ijrobp.2021.12.173.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerBreast-conserving surgeryStage I HER2-positive breast cancerT-DM1 armBreast radiation therapyT-DM1Radiation therapySkin toxicityBreast cancerBCS patientsWBRT patientsInvasive disease-free survival eventsDisease-free survival eventsInvasive disease-free survivalHuman epidermal growth factor receptor 2Phase II Randomized TrialWhole breast radiation therapyEpidermal growth factor receptor 2Adjuvant T-DM1Adjuvant trastuzumab emtansineEfficacy of HER2RT-related toxicityWeeks of therapyAcute skin toxicityAnti-HER2 therapy
2021
SYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM)
Leone J, Tayob N, Pereslete A, Ligibel J, Parsons H, Bi W, Zhao J, Winer E, Lin N. SYST-06. PHASE II TRIAL OF PAXALISIB (GDC-0084) IN COMBINATION WITH TRASTUZUMAB FOR PATIENTS WITH HER2-POSITIVE BREAST CANCER BRAIN METASTASES (BCBM). Neuro-Oncology Advances 2021, 3: iv9-iv9. DOI: 10.1093/noajnl/vdab112.034.Peer-Reviewed Original ResearchBreast cancer brain metastasesObjective response rateCohort BCohort ACNS metastasesPrimary endpointHER2-positive breast cancer brain metastasesNeuro-Oncology Brain Metastases criteriaCentral nervous system metastasesHER2-positive breast cancerPatient-derived xenografts (PDX) modelsPhase II cohortNervous system metastasesPhase II studyCancer brain metastasesPhase II trialPI3K/Akt/mTORPatient-reported outcomesPI3KBrain-penetrant inhibitorAkt/mTORMetastasis (TNM) criteriaBrain metastasesII trialMetastasis resectionHow we treat HER2-positive brain metastases
Stavrou E, Winer EP, Lin NU. How we treat HER2-positive brain metastases. ESMO Open 2021, 6: 100256. PMID: 34482180, PMCID: PMC8424223, DOI: 10.1016/j.esmoop.2021.100256.Peer-Reviewed Original ResearchConceptsHER2-positive brain metastasesHuman epidermal growth factor 2Brain metastasesAdvanced diseaseBreast cancerCentral nervous system metastasesHER2-positive breast cancerEpidermal growth factor 2Nervous system metastasesExperienced multidisciplinary teamSurvival of patientsCentral nervous system activitySite of diseaseNervous system activityUnique clinical challengesAssociated morbiditySystemic therapyGrowth factor 2Clinical challengeReview of agentsClinical scenariosMultidisciplinary teamMetastasisSystem activityDiseaseAdjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxelUpdated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. Journal Of Clinical Oncology 2021, 39: 2247-2256. PMID: 33999652, PMCID: PMC8260904, DOI: 10.1200/jco.21.00280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleFluorodeoxyglucose F18HumansMiddle AgedNeoadjuvant TherapyPositron Emission Tomography Computed TomographyPredictive Value of TestsRadiopharmaceuticalsReceptor, ErbB-2Time FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsPositron emission tomography-computed tomographyFluorodeoxyglucose positron emission tomography-computed tomographyHER2-positive breast cancerEmission tomography-computed tomographyPathologic complete responseTomography-computed tomographyStandardized uptake valueBreast cancerComplete responseUptake valuePercent changeOne-sided type ITumor maximum standardized uptake valueHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Maximum standardized uptake valuePathological complete responseGrowth factor receptor 2Median percent reductionPositive breast cancerTailoring of therapyLean body massReceiver operator characteristic analysisFactor receptor 2Operator characteristic analysisImpact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell'Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discovery 2021, 11: candisc.1557.2020. PMID: 33941592, PMCID: PMC8598376, DOI: 10.1158/2159-8290.cd-20-1557.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-positive early-stage breast cancerTherapeutic resistancePathologic complete response rateEarly-stage breast cancerNeoadjuvant clinical trialsComplete response rateSubset of patientsHER2 therapyPretreatment biopsiesEvaluable casesCure rateT-DM1Trastuzumab emtansineClinical trialsTreatment strategiesTreatment responseTreatment selectionResponse rateRelated commentaryTherapyIssue feature