2023
Correlation 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 regression
2022
Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update
Ramakrishna N, Anders CK, Lin NU, Morikawa A, Temin S, Chandarlapaty S, Crews JR, Davidson NE, Franzoi MAB, Kirshner JJ, Krop IE, Patt DA, Perlmutter J, Giordano SH. Management of Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases: ASCO Guideline Update. Journal Of Clinical Oncology 2022, 40: 2636-2655. PMID: 35640075, DOI: 10.1200/jco.22.00520.Peer-Reviewed Original ResearchConceptsWhole brain radiotherapyAdvanced breast cancerBrain metastasesSystemic therapyBreast cancerLocal therapyGuideline recommendationsAdvanced human epidermal growth factor receptorHER2-positive advanced breast cancerPositive advanced breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorAppropriate local therapyASCO Guideline UpdateBest supportive careProgression-free survivalSize of metastasesGrowth factor receptor 2Presence of symptomsRoutine magnetic resonanceFactor receptor 2Outcomes of interestMagnetic resonance imagingEpidermal growth factor receptor
2021
Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsA phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer
Balch SM, Vaz-Luis I, Li T, Tayob N, Jain E, Helvie K, Buendia-Buendia JE, Shannon E, Isakoff SJ, Tung NM, Krop IE, Lin NU, Wagle N, Freedman RA. A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer. Breast Cancer Research And Treatment 2021, 189: 411-423. PMID: 34302589, DOI: 10.1007/s10549-021-06329-x.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Objective response ratePhase II studyWhole-exome sequencingEribulin 1.4II studyTreatment landscapeCohort AEribulin mesylateDay 1Genomic alterationsMetastatic breast cancer settingEpidermal growth factor receptor 2More frequent alterationsBreast cancer settingModest clinical activityGrowth factor receptor 2Metastatic breast cancerResponse/resistanceFactor receptor 2Manageable toxicityPertuzumab exposurePrimary endpointSix patientsCohort BTrial in progress: A phase 1b/2 study of the PARP inhibitor niraparib in combination with trastuzumab in patients with metastatic HER2+ breast cancer (TBCRC 050).
Stringer-Reasor E, Li Y, Witherspoon F, Specht J, Del Santo Anampa Mesias J, Nanda R, Dees E, Wolff A, Krop I, Lin N, Rimawi M, Yang E. Trial in progress: A phase 1b/2 study of the PARP inhibitor niraparib in combination with trastuzumab in patients with metastatic HER2+ breast cancer (TBCRC 050). Journal Of Clinical Oncology 2021, 39: tps1098-tps1098. DOI: 10.1200/jco.2021.39.15_suppl.tps1098.Peer-Reviewed Original ResearchHuman epidermal growth factor receptor 2Metastatic human epidermal growth factor receptor 2Dose-limiting toxicityBreast cancerResponse rateBC cellsEpidermal growth factor receptor 2Single-arm clinical trialECOG PS 0Efficacy of niraparibObjective response ratePhase 1b/2 studyGrowth factor receptor 2Arm clinical trialPARP inhibitor niraparibFactor receptor 2Poly (ADP-ribose) polymerase (PARP) inhibitorsNF-kB signalingMeasurable diseasePhase 1b/2Accrual goalEligible patientsPS 0Clinical benefitCNS diseaseUpdated 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 analysisThe impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer
Janiszewska M, Stein S, Filho O, Eng J, Kingston NL, Harper NW, Rye IH, Alečković M, Trinh A, Murphy KC, Marangoni E, Cristea S, Oakes B, Winer EP, Krop I, Russnes HG, Spellman PT, Bucher E, Hu Z, Chin K, Gray JW, Michor F, Polyak K. The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer. JCI Insight 2021, 6: e147617. PMID: 33886505, PMCID: PMC8262355, DOI: 10.1172/jci.insight.147617.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA Copy Number VariationsDrug Resistance, NeoplasmEpithelial CellsFemaleFibroblastsHumansMacrophagesMiddle AgedMutationNeoplasm TransplantationReceptor, ErbB-2TrastuzumabTumor MicroenvironmentVesicular Transport ProteinsConceptsBreast cancerTherapeutic resistanceHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Patient-derived xenograft modelsLymphatic vessel endothelial hyaluronan receptorHER2-targeted therapiesGrowth factor receptor 2Impact of tumorFibroblastic reticular cellsFactor receptor 2Tumor epithelial cellsIntratumor heterogeneityDivergent cellular phenotypesResistance-conferring mutationsClinical outcomesPIK3CA mutationsTreatment responseClinical challengeDifferent therapiesFrequency of cellsXenograft modelReceptor 2Stromal determinants
2020
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal Of Clinical Oncology 2020, 38: 4274-4282. PMID: 33119476, DOI: 10.1200/jco.20.02151.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerObjective response rateProgression-free survivalPoly (ADP-ribose) polymerase (PARP) inhibitorsPhase II studyBreast cancerMutation carriersII studyMedian progression-free survivalNegative metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical benefit rateHER2-negative diseasePlatinum-refractory diseaseGrowth factor receptor 2Population of patientsFactor receptor 2Homologous recombination-related genesConfirmed responsesEligible patientsMeasurable diseaseSecondary endpointsChemotherapy regimensPrimary endpointSurvival, 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 benefit3O Mutation analysis of circulating tumour DNA from baseline and study discontinuation samples in SANDPIPER, a phase III study of taselisib or placebo with fulvestrant in oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutant advanced breast cancer
Jacot W, Savage H, Dent S, Cortés J, Im Y, Dieras V, Harbeck N, Krop I, Chen J, Sokol E, Schimmoller F, Hsu J, De Laurentiis M, Wilson T. 3O Mutation analysis of circulating tumour DNA from baseline and study discontinuation samples in SANDPIPER, a phase III study of taselisib or placebo with fulvestrant in oestrogen receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutant advanced breast cancer. Annals Of Oncology 2020, 31: s16. DOI: 10.1016/j.annonc.2020.03.139.Peer-Reviewed Original ResearchTBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial).
Tung N, Arun B, Hacker MR, Hofstatter E, Toppmeyer DL, Isakoff SJ, Borges V, Legare RD, Isaacs C, Wolff AC, Marcom PK, Mayer EL, Lange PB, Goss AJ, Jenkins C, Krop IE, Winer EP, Schnitt SJ, Garber JE. TBCRC 031: Randomized Phase II Study of Neoadjuvant Cisplatin Versus Doxorubicin-Cyclophosphamide in Germline BRCA Carriers With HER2-Negative Breast Cancer (the INFORM trial). Journal Of Clinical Oncology 2020, 38: 1539-1548. PMID: 32097092, PMCID: PMC8462533, DOI: 10.1200/jco.19.03292.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerResidual cancer burden scoreBreast cancerDoxorubicin-cyclophosphamideRisk ratioStage IPathologic complete response rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Single-agent cisplatinComplete response ratePhase II studyPhase II trialGrowth factor receptor 2Positive breast cancerNegative breast cancerFactor receptor 2CT1-3II trialII studyNodal involvementPCR rateNegative diseasePathologic responseAntitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study
Modi S, Park H, Murthy RK, Iwata H, Tamura K, Tsurutani J, Moreno-Aspitia A, Doi T, Sagara Y, Redfern C, Krop IE, Lee C, Fujisaki Y, Sugihara M, Zhang L, Shahidi J, Takahashi S. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low–Expressing Advanced Breast Cancer: Results From a Phase Ib Study. Journal Of Clinical Oncology 2020, 38: 1887-1896. PMID: 32058843, PMCID: PMC7280051, DOI: 10.1200/jco.19.02318.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseHER2-low breast cancerT-DXdBreast cancerTrastuzumab deruxtecanAntitumor activityConfirmed objective response rateTopoisomerase I inhibitor payloadTreatment-emergent adverse eventsHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer refractoryIndependent adjudication committeeObjective response ratePhase Ib studyAdvanced breast cancerGrowth factor receptor 2Preliminary antitumor activityIndependent central reviewWithdrawal of consentFactor receptor 2Cancer refractoryEligible patientsMetastatic HER2Unacceptable toxicity
2019
Tucatinib, 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 2TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases
Freedman RA, Gelman RS, Anders CK, Melisko ME, Parsons HA, Cropp AM, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Connolly RM, Moy B, Van Poznak CH, Blackwell KL, Puhalla SL, Jankowitz RC, Smith KL, Ibrahim N, Moynihan TJ, O’Sullivan C, Nangia J, Niravath P, Tung N, Pohlmann PR, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, . TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer and Brain Metastases. Journal Of Clinical Oncology 2019, 37: jco.18.01511. PMID: 30860945, PMCID: PMC6494354, DOI: 10.1200/jco.18.01511.Peer-Reviewed Original ResearchConceptsCNS objective response rateObjective response rateHER2-positive breast cancer brain metastasesBreast cancer brain metastasesCancer brain metastasesBrain metastasesBreast cancerCommon grade 3 toxicitiesHER2-positive brain metastasesMedian progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Human epidermal growth factor receptorEfficacy of HER2Non-CNS progressionGrade 3 toxicityPrimary end pointPhase II trialProgression-free survivalGrowth factor receptor 2Positive breast cancerProgressive neurologic signsEvidence-based treatmentsFactor receptor 2Epidermal growth factor receptorTBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic 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. TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. Journal Of Clinical Oncology 2019, 37: jco.2018.78.7986. PMID: 30721110, PMCID: PMC6424139, DOI: 10.1200/jco.2018.78.7986.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleFluorodeoxyglucose F18HumansMiddle AgedNeoadjuvant TherapyNeoplasm StagingPredictive Value of TestsRadiopharmaceuticalsReceptor, ErbB-2Receptors, EstrogenSingle Photon Emission Computed Tomography Computed TomographyTime FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsPathologic complete responseHER2-positive breast cancerPositron emission tomography/Emission tomography/Standardized uptake valueBreast cancerComplete responseTomography/Uptake valueTumor maximum standardized uptake valueOne-sided type IHuman epidermal growth factor receptor 2Stage II/IIIEpidermal growth factor receptor 2Maximum standardized uptake valueCycles of PTGrowth factor receptor 2Median percent reductionPositive breast cancerLean body massFactor receptor 2Significant differencesEvaluable patientsNeoadjuvant pertuzumabPT initiation
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
HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer
Miller K, Cortes J, Hurvitz SA, Krop IE, Tripathy D, Verma S, Riahi K, Reynolds JG, Wickham TJ, Molnar I, Yardley DA. HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer. BMC Cancer 2016, 16: 352. PMID: 27259714, PMCID: PMC4893300, DOI: 10.1186/s12885-016-2385-z.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerProgression-free survivalPhase 2 trialMetastatic breast cancerBreast cancerDisease progressionOverall survivalMM-302Physician's choiceInvestigator-assessed progression-free survivalMetastatic HER2-positive breast cancerRandomized phase 2 trialEpidermal growth factor receptor 2Anthracycline-naïve patientsBackgroundHuman epidermal growth factor receptor 2Objective response rateGrowth factor receptor 2Positive breast cancerAdo-trastuzumab emtansineKey inclusion criteriaFactor receptor 2Quality of lifeOS ratesRECIST v1.1Refractory HER2Cardiac 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 HER2The Evolving Landscape of HER2 Targeting in Breast Cancer
Moasser MM, Krop IE. The Evolving Landscape of HER2 Targeting in Breast Cancer. JAMA Oncology 2015, 1: 1154. PMID: 26204261, DOI: 10.1001/jamaoncol.2015.2286.Peer-Reviewed Original ResearchConceptsTreatment of HER2Breast cancerImmunologic effectorsHER2 targetingSubstantial single-agent activityHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Value of HER2Lines of therapyGrowth factor receptor 2Single-agent activityLate-stage diseaseStage of diseaseUseful predictive biomarkerHER2 inhibitor lapatinibFactor receptor 2Variety of cytotoxicModest efficacyTrastuzumab resistancePredictive biomarkersCell surface expressionImmunologic activityInhibitor lapatinibReceptor 2Advanced stage