2021
Genomic Characterization of de novo Metastatic Breast Cancer
Garrido-Castro AC, Spurr LF, Hughes ME, Li YY, Cherniack AD, Kumari P, Lloyd MR, Bychkovsky B, Barroso-Sousa R, Di Lascio S, Jain E, Files J, Mohammed-Abreu A, Krevalin M, MacKichan C, Barry WT, Guo H, Xia D, Cerami E, Rollins BJ, MacConaill LE, Lindeman NI, Krop IE, Johnson BE, Wagle N, Winer EP, Dillon DA, Lin NU. Genomic Characterization of de novo Metastatic Breast Cancer. Clinical Cancer Research 2021, 27: 1105-1118. PMID: 33293374, PMCID: PMC7887078, DOI: 10.1158/1078-0432.ccr-20-1720.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPrimary tumorOverall survivalBreast cancerDe novo metastatic breast cancerNovo metastatic breast cancerDifferential therapeutic sensitivityBetter OSPoor OSShorter OSInitial diagnosisHigh TMBMetastatic tumorsDnMBCCurrent treatmentMutational burdenTreatment selectionMetastatic driversStage IMultiple comparison adjustmentTherapeutic sensitivityTumorsPatientsCancerIntrinsic resistance
2020
Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases
Leone JP, Emblem KE, Weitz M, Gelman RS, Schneider BP, Freedman RA, Younger J, Pinho MC, Sorensen AG, Gerstner ER, Harris G, Krop IE, Morganstern D, Sohl J, Hu J, Kasparian E, Winer EP, Lin NU. Phase II trial of carboplatin and bevacizumab in patients with breast cancer brain metastases. Breast Cancer Research 2020, 22: 131. PMID: 33256829, PMCID: PMC7706261, DOI: 10.1186/s13058-020-01372-w.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBrainBrain NeoplasmsBreastBreast NeoplasmsCarboplatinFemaleGenotyping TechniquesHumansKaplan-Meier EstimateMagnetic Resonance ImagingMiddle AgedPolymorphism, Single NucleotideProgression-Free SurvivalTrastuzumabVascular Endothelial Growth Factor AConceptsProgression-free survivalBreast cancer brain metastasesEarly MRI changesCancer brain metastasesBrain metastasesOverall survivalMRI changesBreast cancerEastern Cooperative Oncology Group performance statusDay 1Cycle 1 day 1Cycle 1 day 8Median progression-free survivalWorse progression-free survivalRegimen warrants further investigationDurable objective responsesECOG PS 1Efficacy of bevacizumabHER2-positive diseaseProgressive brain metastasesResultsThirty-eight patientsMedian overall survivalObjective response ratePhase II trialContrast-enhanced brain MRI
2019
Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer
Modi S, Saura C, Yamashita T, Park YH, Kim SB, Tamura K, Andre F, Iwata H, Ito Y, Tsurutani J, Sohn J, Denduluri N, Perrin C, Aogi K, Tokunaga E, Im SA, Lee KS, Hurvitz SA, Cortes J, Lee C, Chen S, Zhang L, Shahidi J, Yver A, Krop I. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer. New England Journal Of Medicine 2019, 382: 610-621. PMID: 31825192, PMCID: PMC7458671, DOI: 10.1056/nejmoa1914510.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCamptothecinConsolidation ChemotherapyFemaleHumansImmunoconjugatesIntention to Treat AnalysisKaplan-Meier EstimateLung Diseases, InterstitialMiddle AgedProgression-Free SurvivalReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerHER2-positive breast cancerProgression-free survivalTrastuzumab deruxtecanInterstitial lung diseaseBreast cancerMedian durationLung diseaseTrastuzumab emtansinePhase 1 dose-finding studyAdvanced HER2-positive breast cancerKey secondary end pointEnd pointPrevious treatmentClinical benefit rateDecreased neutrophil countCommon adverse eventsDisease control rateMedian response durationPrimary end pointSecondary end pointsPhase 2 studySubgroup of patientsDurable antitumor activityTucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer
Murthy RK, Loi S, Okines A, Paplomata E, Hamilton E, Hurvitz SA, Lin NU, Borges V, Abramson V, Anders C, Bedard PL, Oliveira M, Jakobsen E, Bachelot T, Shachar SS, Müller V, Braga S, Duhoux FP, Greil R, Cameron D, Carey LA, Curigliano G, Gelmon K, Hortobagyi G, Krop I, Loibl S, Pegram M, Slamon D, Palanca-Wessels MC, Walker L, Feng W, Winer EP. Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. New England Journal Of Medicine 2019, 382: 597-609. PMID: 31825569, DOI: 10.1056/nejmoa1914609.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreast NeoplasmsCapecitabineConsolidation ChemotherapyDiarrheaDouble-Blind MethodFemaleHumansKaplan-Meier EstimateMiddle AgedOxazolesProgression-Free SurvivalProtein-Tyrosine KinasesPyridinesQuinazolinesReceptor, ErbB-2TrastuzumabConceptsHER2-positive metastatic breast cancerProgression-free survivalPlacebo-combination groupMetastatic breast cancerElevated aminotransferase levelsBrain metastasesBreast cancerOverall survivalAminotransferase levelsMedian progression-free survivalPalmar-plantar erythrodysesthesia syndromeBetter progression-free survivalPositive metastatic breast cancerHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Common adverse eventsMedian overall survivalObjective response ratePrimary end pointSecondary end pointsGrowth factor receptor 2Overall survival outcomesRisk of diarrheaFactor receptor 2The 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
2018
Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial
Borges VF, Ferrario C, Aucoin N, Falkson C, Khan Q, Krop I, Welch S, Conlin A, Chaves J, Bedard PL, Chamberlain M, Gray T, Vo A, Hamilton E. Tucatinib Combined With Ado-Trastuzumab Emtansine in Advanced ERBB2/HER2-Positive Metastatic Breast Cancer: A Phase 1b Clinical Trial. JAMA Oncology 2018, 4: 1214-1220. PMID: 29955792, PMCID: PMC6143009, DOI: 10.1001/jamaoncol.2018.1812.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsDiarrheaDrug Administration ScheduleFatigueFemaleHumansKaplan-Meier EstimateMaytansineMiddle AgedNauseaNeoplasm MetastasisProtein Kinase InhibitorsReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsTrastuzumabConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdo-trastuzumab emtansineT-DM1Breast cancerTyrosine kinase inhibitorsBrain metastasesAdverse eventsClinical trialsToxic reactionsDose-limiting toxic reactionHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Phase 1b clinical trialGrowth factor receptor 2ERBB2/HER2-positive breast cancerPreliminary antitumor activityTreatment of patientsSpecific tyrosine kinase inhibitorYears of ageDrug-drug interactionsFactor receptor 2Hepatic transaminitisHER2 therapy
2016
Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T‐DM1) vs. treatment of physician's choice in previously treated HER2‐positive advanced breast cancer
Kim S, Wildiers H, Krop IE, Smitt M, Yu R, de Haas S, Gonzalez‐Martin A. Relationship between tumor biomarkers and efficacy in TH3RESA, a phase III study of trastuzumab emtansine (T‐DM1) vs. treatment of physician's choice in previously treated HER2‐positive advanced breast cancer. International Journal Of Cancer 2016, 139: 2336-2342. PMID: 27428671, DOI: 10.1002/ijc.30276.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCapecitabineClass I Phosphatidylinositol 3-KinasesFemaleHumansKaplan-Meier EstimateLapatinibMaytansinePhosphatidylinositol 3-KinasesQuinazolinesReceptor, ErbB-2Trastuzumab
2013
A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer
Tolaney SM, Najita J, Sperinde J, Huang W, Chen WY, Savoie J, Fornier M, Winer EP, Bunnell C, Krop IE. A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer. Annals Of Oncology 2013, 24: 1841-1847. PMID: 23559151, PMCID: PMC3690910, DOI: 10.1093/annonc/mdt121.Peer-Reviewed Original ResearchConceptsMetastatic HER2-positive breast cancerHER2-positive breast cancerCombination of ixabepilonePhase II studyBreast cancerII studyMetastatic diseaseCohort 2Cohort 1Treatment-related toxic effectsClinical benefit rateSubsequent-line therapyTrastuzumab-containing regimensMetastatic breast cancerPrior chemotherapyLine therapyBenefit rateOverall RRDay 1PatientsTrastuzumabIxabepiloneCancerTumor biomarkersCohort
2012
Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer
Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K. Trastuzumab Emtansine for HER2-Positive Advanced Breast Cancer. New England Journal Of Medicine 2012, 367: 1783-1791. PMID: 23020162, PMCID: PMC5125250, DOI: 10.1056/nejmoa1209124.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapecitabineDeoxycytidineDisease-Free SurvivalFemaleFluorouracilHumansIntention to Treat AnalysisKaplan-Meier EstimateLapatinibMaytansineMiddle AgedNeoplasm MetastasisQuinazolinesReceptor, ErbB-2Survival RateTrastuzumabYoung AdultConceptsHER2-positive advanced breast cancerAdvanced breast cancerProgression-free survivalObjective response rateSecondary end pointsT-DM1Overall survivalBreast cancerEnd pointTrastuzumab emtansineInterim analysisResponse rateAdditional secondary end pointsMedian progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Incidence of thrombocytopeniaMedian overall survivalPrimary end pointSerum aminotransferase levelsPalmar-plantar erythrodysesthesiaSecond interim analysisGrowth factor receptor 2Incidence of diarrheaFactor receptor 2
2011
Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy
Morrow PK, Wulf GM, Ensor J, Booser DJ, Moore JA, Flores PR, Xiong Y, Zhang S, Krop IE, Winer EP, Kindelberger DW, Coviello J, Sahin AA, Nuñez R, Hortobagyi GN, Yu D, Esteva FJ. Phase I/II Study of Trastuzumab in Combination With Everolimus (RAD001) in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Progressed on Trastuzumab-Based Therapy. Journal Of Clinical Oncology 2011, 29: 3126-3132. PMID: 21730275, PMCID: PMC3157979, DOI: 10.1200/jco.2010.32.2321.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsDisease-Free SurvivalEverolimusFemaleHumansImmunohistochemistryKaplan-Meier EstimateMiddle AgedNeoplasm MetastasisPTEN PhosphohydrolaseReceptor, ErbB-2Salvage TherapySirolimusTOR Serine-Threonine KinasesTrastuzumabConceptsHER2-overexpressing metastatic breast cancerMetastatic breast cancerProgression-free survivalCombination of everolimusTrastuzumab-based therapyPTEN lossBreast cancerPhase I/II studyMedian progression-free survivalDana-Farber Cancer InstituteTexas MD Anderson Cancer CenterMD Anderson Cancer CenterBeth Israel Deaconess Medical CenterClinical benefit ratePersistent stable diseaseAnderson Cancer CenterDownstream mammalian targetDaily everolimusNonhematologic toxicityStable diseaseII studyOverall survivalPartial responseHER2 overexpressingClinical benefitResponses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer
Olson EM, Lin NU, DiPiro PJ, Najita JS, Krop IE, Winer EP, Burstein HJ. Responses to subsequent anti-HER2 therapy after treatment with trastuzumab-DM1 in women with HER2-positive metastatic breast cancer. Annals Of Oncology 2011, 23: 93-97. PMID: 21531783, PMCID: PMC3276325, DOI: 10.1093/annonc/mdr061.Peer-Reviewed Original ResearchConceptsAnti-HER2 therapyMetastatic breast cancerHER2-positive MBC patientsT-DM1MBC patientsBreast cancerHER2-positive metastatic breast cancerSingle-agent T-DM1Positive metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Blinded radiology reviewAnti-HER2 agentsGrowth factor receptor 2Kaplan-Meier estimatesFurther clinical benefitFactor receptor 2Protocol therapyMedian durationFurther therapyPartial responseRadiology reviewClinical benefitSubsequent linesMetastatic therapy
2010
Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy
Burris HA, Rugo HS, Vukelja SJ, Vogel CL, Borson RA, Limentani S, Tan-Chiu E, Krop IE, Michaelson RA, Girish S, Amler L, Zheng M, Chu YW, Klencke B, O'Shaughnessy JA. Phase II Study of the Antibody Drug Conjugate Trastuzumab-DM1 for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2) –Positive Breast Cancer After Prior HER2-Directed Therapy. Journal Of Clinical Oncology 2010, 29: 398-405. PMID: 21172893, DOI: 10.1200/jco.2010.29.5865.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsDisease-Free SurvivalFemaleHumansImmunotoxinsKaplan-Meier EstimateMaytansineMiddle AgedReceptor, ErbB-2RNA, MessengerTime FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsHER2-positive metastatic breast cancerMetastatic breast cancerPhase II studyTrastuzumab-DM1II studyAdverse eventsResponse rateBreast cancerHER2 levelsMedian progression-free survival timeSingle-arm phase II studyRobust single-agent activityProgression-free survival timeHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorHER2-directed therapiesMaximum-tolerated doseMost adverse eventsObjective response ratePhase II doseGrowth factor receptor 2Single-agent activityHER2-positive tumorsReverse transcriptase-polymerase chain reaction