2024
TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer
Lynce F, Stevens L, Li Z, Brock J, Gulvady A, Huang Y, Nakhlis F, Patel A, Force J, Haddad T, Ueno N, Stearns V, Wolff A, Clark A, Bellon J, Richardson E, Balko J, Krop I, Winer E, Lange P, Hwang E, King T, Tolaney S, Thompson A, Gupta G, Mittendorf E, Regan M, Overmoyer B, Polyak K. TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer. Breast Cancer Research 2024, 26: 20. PMID: 38297352, PMCID: PMC10829369, DOI: 10.1186/s13058-024-01774-0.Peer-Reviewed Original ResearchConceptsInflammatory breast cancerPathological complete responseTriple-negative IBCPhase II studyTN-IBCIL-6/JAK/STAT3 signalingBreast cancerRandomized phase II studyRun-inInvestigation of novel therapiesDoxorubicin plus cyclophosphamideTreatment naive patientsImmune suppressive effectsGrowth inhibitory effectNeoadjuvant therapyPreoperative therapyComplete responsePhosphorylated STAT3Tumor biopsiesWorse survivalII studyPrimary endpointSecondary endpointsImmune suppressionT cells
2023
Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab
Waks A, Ogayo E, Paré L, Marín-Aguilera M, Brasó-Maristany F, Galván P, Castillo O, Martínez-Sáez O, Vivancos A, Villagrasa P, Villacampa G, Tarantino P, Desai N, Guerriero J, Metzger O, Tung N, Krop I, Parker J, Perou C, Prat A, Winer E, Tolaney S, Mittendorf E. Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab. JAMA Oncology 2023, 9: 835-840. PMID: 37103927, PMCID: PMC10141272, DOI: 10.1001/jamaoncol.2023.0181.Peer-Reviewed Original ResearchConceptsPathologic complete responseNeoadjuvant therapyPCR scoresNeoadjuvant paclitaxelBreast cancerPrognostic studiesRisk scoreLikelihood of pCRPretreatment tumor biopsy samplesErbB2-positive breast cancerBaseline tumor samplesLimited clinical featuresFavorable survival outcomesHormone receptor statusPositive breast cancerPrognostic risk scoreTumor biopsy samplesPaclitaxel weeklyComplete responsePCR rateReceptor statusClinical featuresMean ageSurvival outcomesRecurrence eventsImpact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial.
Weiss A, Li T, Desai N, Tung N, Poorvu P, Partridge A, Nakhlis F, Dominici L, Sinclair N, Spring L, Faggen M, Constantine M, Krop I, DeMeo M, Wrabel E, Alberti J, Chikarmane S, Tayob N, King T, Tolaney S, Winer E, Mittendorf E, Waks A. Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial. Journal Of The American College Of Surgeons 2023, 237: 247-256. PMID: 37194964, DOI: 10.1097/xcs.0000000000000761.Peer-Reviewed Original ResearchConceptsBreast conservation therapyTrastuzumab/pertuzumabBreast cancerTumor downsizingSystemic therapyBCT ratesSingle-arm prospective clinical trialBreast pathologic complete responseSingle-arm prospective trialBreast cancer warrants further investigationBCT-eligible patientsBreast size ratioCancer warrants further investigationEarly-stage HER2Neoadjuvant systemic therapyPathologic complete responseProspective clinical trialsWarrants further investigationBCT eligibilityMulticentric tumorsNeoadjuvant regimensProspective trialComplete responseLocal therapyConservation therapyPrognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer
Fernandez-Martinez A, Pascual T, Singh B, Nuciforo P, Rashid N, Ballman K, Campbell J, Hoadley K, Spears P, Pare L, Brasó-Maristany F, Chic N, Krop I, Partridge A, Cortés J, Llombart-Cussac A, Prat A, Perou C, Carey L. Prognostic and Predictive Value of Immune-Related Gene Expression Signatures vs Tumor-Infiltrating Lymphocytes in Early-Stage ERBB2/HER2-Positive Breast Cancer. JAMA Oncology 2023, 9: 490-499. PMID: 36602784, PMCID: PMC9857319, DOI: 10.1001/jamaoncol.2022.6288.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunoglobulin GLapatinibLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyPaclitaxelPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TranscriptomeTrastuzumabTreatment OutcomeConceptsEvent-free survivalHER2-positive breast cancerPathologic complete responseERBB2/HER2-positive breast cancerPrimary end pointGene expression signaturesBreast cancerEnd pointImmune signaturesPretreatment tumorPrognostic valueExpression signaturesHigher pathologic complete responseMultivariable Cox modelSecondary end pointsAdditive prognostic valueTumor-Infiltrating LymphocytesIntrinsic tumor subtypesWeekly paclitaxelNeoadjuvant treatmentClinicopathologic factorsComplete responseCox analysisMedian ageImmune activationAdjuvant 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 ResearchMeSH KeywordsBreastBreast NeoplasmsFemaleHumansMaleMiddle AgedNeoplasm Recurrence, LocalPaclitaxelTrastuzumabConceptsHER2-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
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
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
Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial)
Ruddy KJ, Zheng Y, Tayob N, Hu J, Dang CT, Yardley DA, Isakoff SJ, Valero VV, Faggen MG, Mulvey TM, Bose R, Sella T, Weckstein DJ, Wolff AC, Reeder-Hayes KE, Rugo HS, Ramaswamy B, Zuckerman DS, Hart LL, Gadi VK, Constantine M, Cheng KL, Briccetti FM, Schneider BP, Merrill Garrett A, Kelly Marcom P, Albain KS, DeFusco PA, Tung NM, Ardman BM, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu MC, Rosenberg S, DeMeo MK, Burstein HJ, Winer EP, Krop IE, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial). Breast Cancer Research And Treatment 2021, 189: 103-110. PMID: 34120223, DOI: 10.1007/s10549-021-06267-8.Peer-Reviewed Original ResearchConceptsChemotherapy-related amenorrheaEarly-stage breast cancerRisk of infertilityAdo-trastuzumab emtansineT-DM1Gonadotropin-releasing hormone agonistAdjuvant T-DM1T-DM1 3.6Amenorrhea ratesPermanent menopauseStandard HER2Chemotherapy regimensPrimary endpointProtocol therapyMedian ageOvarian toxicityPremature menopauseHormone agonistBreast cancerMenstrual dataMonthsAmenorrheaEmtansineMenopauseTrastuzumabAdjuvant 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 toxicityWeeksTrastuzumabCancerPaclitaxel
2020
Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer
Axelrod ML, Nixon MJ, Gonzalez-Ericsson PI, Bergman RE, Pilkinton MA, McDonnell WJ, Sanchez V, Opalenik SR, Loi S, Zhou J, Mackay S, Rexer BN, Abramson VG, Jansen VM, Mallal S, Donaldson J, Tolaney SM, Krop IE, Garrido-Castro AC, Marotti JD, Shee K, Miller TW, Sanders ME, Mayer IA, Salgado R, Balko JM. Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer. Clinical Cancer Research 2020, 26: 5668-5681. PMID: 32826327, PMCID: PMC7642197, DOI: 10.1158/1078-0432.ccr-19-3685.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlbuminsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCD8-Positive T-LymphocytesFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyNeoplasm ProteinsNeoplasm Recurrence, LocalPaclitaxelPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalTreatment OutcomeTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsTriple-negative breast cancerTumor immune microenvironmentNeoadjuvant chemotherapyOverall survivalBreast cancerPeripheral bloodResidual diseaseMetastatic triple-negative breast cancerEffect of NACImproved long-term outcomesActive antitumor immunityLocal tumor immunityRole of chemotherapyT-cell signatureLong-term outcomesPeripheral T cellsMultiple immune-related genesImmune-related genesNab-paclitaxelImmunologic effectsMicrometastatic diseasePersistent diseaseAntitumor immunityTumor immunityClinical outcomesSurvival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer.
Fernandez-Martinez A, Krop IE, Hillman DW, Polley MY, Parker JS, Huebner L, Hoadley KA, Shepherd J, Tolaney S, Henry NL, Dang C, Harris L, Berry D, Hahn O, Hudis C, Winer E, Partridge A, Perou CM, Carey LA. Survival, Pathologic Response, and Genomics in CALGB 40601 (Alliance), a Neoadjuvant Phase III Trial of Paclitaxel-Trastuzumab With or Without Lapatinib in HER2-Positive Breast Cancer. Journal Of Clinical Oncology 2020, 38: 4184-4193. PMID: 33095682, PMCID: PMC7723687, DOI: 10.1200/jco.20.01276.Peer-Reviewed Original ResearchConceptsPathologic complete responseRelapse-free survivalHuman epidermal growth factor receptor 2HER2-positive breast cancerBetter relapse-free survivalOverall survivalCALGB 40601Breast cancerImmune signaturesGene expression signaturesDe-escalation treatment strategiesPrediction of pCREnd pointEpidermal growth factor receptor 2Shorter relapse-free survivalPrimary end pointResidual disease groupSecondary end pointsUntreated stage IIGood prognostic factorGrowth factor receptor 2Phase III trialsExpression signaturesFactor receptor 2OS benefitTBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker
Mayer EL, Abramson V, Jankowitz R, Falkson C, Marcom PK, Traina T, Carey L, Rimawi M, Specht J, Miller K, Stearns V, Tung N, Perou C, Richardson AL, Componeschi K, Trippa L, Tan-Wasielewski Z, Timms K, Krop I, Wolff AC, Winer EP. TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker. Annals Of Oncology 2020, 31: 1518-1525. PMID: 32798689, PMCID: PMC8437015, DOI: 10.1016/j.annonc.2020.08.2064.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerHomologous recombination deficiencyPhase II studyPathologic responsePreoperative cisplatinII studyBreast cancerProspective phase II studyEffective predictive biomarkersInadequate clinical responsePreoperative chemotherapy regimenSingle-agent cisplatinHomologous recombination deficiency biomarkersGermline BRCA1/2Preoperative paclitaxelChemotherapy regimenClinical responseCisplatin chemotherapyPredictive biomarkersAlternative chemotherapyPreoperative trialInadequate responseHRD scoreStage IBaseline tissue
2019
A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer
Abramson VG, Oliveira M, Cervantes A, Wildiers H, Patel MR, Bauer TM, Bedard PL, Becerra C, Richey S, Wei MC, Reyner E, Bond J, Cui N, Wilson TR, Moore HM, Saura C, Krop IE. A phase Ib, open-label, dose-escalation study of the safety and pharmacology of taselisib (GDC-0032) in combination with either docetaxel or paclitaxel in patients with HER2-negative, locally advanced, or metastatic breast cancer. Breast Cancer Research And Treatment 2019, 178: 121-133. PMID: 31368034, DOI: 10.1007/s10549-019-05360-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinoma, Non-Small-Cell LungClass I Phosphatidylinositol 3-KinasesDocetaxelFemaleHumansImidazolesLung NeoplasmsMaleMaximum Tolerated DoseMiddle AgedMutationNeoplasm MetastasisOxazepinesPaclitaxelReceptor, ErbB-2Survival AnalysisTreatment OutcomeConceptsNon-small cell lung cancerDose-limiting toxicityMetastatic breast cancerAdverse eventsBreast cancerPhase IbClinical benefit rateDose-expansion studyObjective response ratePhase II doseSerious adverse eventsDose-escalation studyCell lung cancerBenefit-risk profileDays on/2ResultsEighty patientsPrimary endpointSecondary endpointsSafety profileLung cancerBenefit ratePatientsSingle agentResponse rateDocetaxelLocal–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial)
Bellon JR, Guo H, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Hudis CA, Krop I, Burstein HJ, Winer EP, Tolaney SM. Local–regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial). Breast Cancer Research And Treatment 2019, 176: 303-310. PMID: 31004299, DOI: 10.1007/s10549-019-05238-4.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerLocal-regional recurrenceDisease-free survivalEffective anti-HER2 therapyLRR-free survivalAnti-HER2 therapyBreast-conserving surgeryBreast cancerRadiation therapySystemic therapyHormone receptor-positive tumorsProspective multi-institutional studyHER2-negative diseaseHER2-positive diseaseNegative axillary nodesEffective systemic therapyProspective multicenter trialEarly-stage patientsKaplan-Meier methodReceptor-positive tumorsHER2-positive tumorsMulti-institutional studyFuture investigational effortsAdjuvant trastuzumabProtocol therapySeven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer B, Partridge AH, Hudis CA, Krop IE, Burstein HJ, Winer EP. Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer. Journal Of Clinical Oncology 2019, 37: jco.19.00066. PMID: 30939096, PMCID: PMC7587424, DOI: 10.1200/jco.19.00066.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBreast NeoplasmsBreast Neoplasms, MaleChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesGene Expression Regulation, NeoplasticGenetic Predisposition to DiseaseGenotypeHumansLymph NodesMaleMiddle AgedPaclitaxelPeripheral Nervous System DiseasesPoisson DistributionPolymorphism, Single NucleotideReceptor, ErbB-2RecurrenceRiskTrastuzumabTreatment OutcomeConceptsDisease-free survivalRecurrence-free intervalSmall HER2-positive tumorsAdjuvant paclitaxelHER2-positive tumorsLong-term outcomesTrastuzumab trialsBreast cancerOverall survivalSmall human epidermal growth factor receptor 2Breast cancer-specific survivalPaclitaxel-induced peripheral neuropathyExcellent long-term outcomesHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Human epidermal growth factor receptorPAM50 intrinsic subtypesCancer-specific survivalPhase II studyPrimary end pointGrowth factor receptor 2Positive breast cancerTreatment of patientsSeven-year followThe immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial
Barroso-Sousa R, Barry WT, Guo H, Dillon D, Tan YB, Fuhrman K, Osmani W, Getz A, Baltay M, Dang C, Yardley D, Moy B, Marcom PK, Mittendorf EA, Krop IE, Winer EP, Tolaney SM. The immune profile of small HER2-positive breast cancers: a secondary analysis from the APT trial. Annals Of Oncology 2019, 30: 575-581. PMID: 30753274, PMCID: PMC8033534, DOI: 10.1093/annonc/mdz047.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorBreastBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansKaplan-Meier EstimateMastectomyMiddle AgedPaclitaxelReceptor, ErbB-2TrastuzumabTumor BurdenTumor MicroenvironmentConceptsHER2-positive breast cancerSmall HER2-positive breast cancersImmune gene signaturesBreast cancerImmune profileAPT trialPD-L1Immune markersImmune microenvironmentSmall HER2-positive tumorsStromal PD-L1 expressionNode-negative breast cancerCell signatureGene signatureHuman epidermal growth factor receptorStromal PD-L1PD-L1 expressionHistological grade 2Luminal B tumorsB cell signaturesBreast cancer trialsHER2-positive tumorsImmune cell signaturesBasal-like tumorsHistological grade 1
2016
Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer
Varadan V, Gilmore H, Miskimen KL, Tuck D, Parsai S, Awadallah A, Krop IE, Winer EP, Bossuyt V, Somlo G, Abu-Khalaf MM, Fenton MA, Sikov W, Harris L. Immune Signatures Following Single Dose Trastuzumab Predict Pathologic Response to PreoperativeTrastuzumab and Chemotherapy in HER2-Positive Early Breast Cancer. Clinical Cancer Research 2016, 22: 3249-3259. PMID: 26842237, PMCID: PMC5439498, DOI: 10.1158/1078-0432.ccr-15-2021.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminsAntineoplastic Agents, ImmunologicalBiomarkers, TumorB-LymphocytesBreast NeoplasmsFemaleGene Expression ProfilingHumansImmunity, InnateLymphocyte ActivationMacrophagesMiddle AgedNeoadjuvant TherapyPaclitaxelProgrammed Cell Death 1 ReceptorReceptor, ErbB-2T-Lymphocytes, Helper-InducerTrastuzumabTreatment OutcomeConceptsPathologic complete responseBreast cancerImmune indicesBrief exposureFollicular helper T (Tfh) cell signatureHER2-positive breast cancerPD-1 positivitySingle-agent trastuzumabTrastuzumab-based therapyT cell activityT-cell signatureImmune cell infiltrationTumor core biopsiesImmune cell activationPreoperative trastuzumabNab-paclitaxelAntitumor immunityImmune signaturesPCR rateComplete responseMulticenter trialPD-1Cell infiltrationCore biopsyIntrinsic subtypesPhase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer
Krop IE, Modi S, LoRusso PM, Pegram M, Guardino E, Althaus B, Lu D, Strasak A, Elias A. Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer. Breast Cancer Research 2016, 18: 34. PMID: 26979312, PMCID: PMC4791863, DOI: 10.1186/s13058-016-0691-7.Peer-Reviewed Original ResearchConceptsClinical benefit ratePhase 1b/2a studyObjective response rateT-DM1Adverse eventsPaclitaxel dosesPeripheral neuropathyBreast cancerHER2-positive advanced breast cancerHER2-positive metastatic breast cancerPhase 2aPhase 1bGrade adverse eventsT-DM1 3.6Advanced breast cancerMetastatic breast cancerDose-escalation approachPre-clinical studiesAnti-tumor activityConclusionsThis regimenExperienced gradeMeasurable diseasePaclitaxel 80Prior therapyResultsThe MTDCardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer
Dang C, Guo H, Najita J, Yardley D, Marcom K, Albain K, Rugo H, Miller K, Ellis M, Shapira I, Wolff AC, Carey LA, Moy B, Groarke J, Moslehi J, Krop I, Burstein HJ, Hudis C, Winer EP, Tolaney SM. Cardiac Outcomes of Patients Receiving Adjuvant Weekly Paclitaxel and Trastuzumab for Node-Negative, ERBB2-Positive Breast Cancer. JAMA Oncology 2016, 2: 1-8. PMID: 26539793, PMCID: PMC5654518, DOI: 10.1001/jamaoncol.2015.3709.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalDrug Administration ScheduleFemaleHumansMiddle AgedNeoplasm StagingPaclitaxelReceptor, ErbB-2Risk AssessmentRisk FactorsStroke VolumeTime FactorsTrastuzumabTreatment OutcomeUnited StatesVentricular Dysfunction, LeftVentricular Function, LeftYoung AdultConceptsErbB2-positive breast cancerAsymptomatic LVEF declineCardiac toxic effectsLVEF declineBreast cancerPatients LVEFGrade 3Early-stage human epidermal growth factor receptor 2Asymptomatic left ventricular ejection fraction declineLeft ventricular ejection fraction declineVentricular ejection fraction declineHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Adjuvant weekly paclitaxelCardiac safety dataEjection fraction declineMedian patient ageVentricular systolic dysfunctionTrastuzumab-based treatmentWeeks of chemotherapyGrowth factor receptor 2Positive breast cancerLife-saving therapyFactor receptor 2Single-group study
2015
Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib
Carey LA, Berry DA, Cirrincione CT, Barry WT, Pitcher BN, Harris LN, Ollila DW, Krop IE, Henry NL, Weckstein DJ, Anders CK, Singh B, Hoadley KA, Iglesia M, Cheang MC, Perou CM, Winer EP, Hudis CA. Molecular Heterogeneity and Response to Neoadjuvant Human Epidermal Growth Factor Receptor 2 Targeting in CALGB 40601, a Randomized Phase III Trial of Paclitaxel Plus Trastuzumab With or Without Lapatinib. Journal Of Clinical Oncology 2015, 34: 542-549. PMID: 26527775, PMCID: PMC4980567, DOI: 10.1200/jco.2015.62.1268.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinomaEstrogen Receptor alphaFemaleGene ExpressionHumansImmunoglobulin GLapatinibMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelQuinazolinesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRNA, MessengerTrastuzumabTreatment OutcomeTumor MicroenvironmentTumor Suppressor Protein p53Young AdultConceptsPathologic complete response rateCALGB 40601Dual therapyIntrinsic subtypesHormone receptor-negative diseaseRandomized phase III trialHuman epidermal growth factor receptor 2End pointHER2-positive breast cancerEpidermal growth factor receptor 2Correlative end pointsDual HER2 blockadeHER2-positive diseaseComplete response ratePrimary end pointPhase III trialsProgression-free survivalReceptor-negative diseaseAddition of lapatinibGrowth factor receptor 2Immune cell signaturesFactor receptor 2Gene expression-based assaysMolecular featuresDual HER2Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial)
Ruddy KJ, Guo H, Barry W, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis MJ, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Hudis C, Krop IE, Burstein HJ, Winer EP, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea after adjuvant paclitaxel–trastuzumab (APT trial). Breast Cancer Research And Treatment 2015, 151: 589-596. PMID: 25981899, PMCID: PMC5057177, DOI: 10.1007/s10549-015-3426-z.Peer-Reviewed Original ResearchConceptsChemotherapy-related amenorrheaChemotherapy initiationMenopausal symptomsBreast cancerAdjuvant breast cancer therapyEarly-stage breast cancerNode-negative HER2Weeks of paclitaxelStage breast cancerLast menstrual periodBreast cancer therapyAdjuvant paclitaxelAmenorrhea ratesAPT trialEligible patientsEvaluable populationPremenopausal womenAdjuvant studiesTrastuzumab monotherapyMedian timeMenstrual periodCancer regimensAmenorrheaTrastuzumabMonths