2021
Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer
O'Sullivan CC, Ballman KV, McCall L, Kommalapati A, Zemla T, Weiss A, Mitchell M, Blinder V, Tung NM, Irvin WJ, Lee M, Goetz MP, Symmans WF, Borges VF, Krop I, Carey LA, Partridge AH. Alliance A011801 (compassHER2 RD): postneoadjuvant T-DM1 + tucatinib/placebo in patients with residual HER2-positive invasive breast cancer. Future Oncology 2021, 17: 4665-4676. PMID: 34636255, PMCID: PMC8600597, DOI: 10.2217/fon-2021-0753.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAntineoplastic Combined Chemotherapy ProtocolsBrain NeoplasmsBreastBreast NeoplasmsChemoradiotherapy, AdjuvantChemotherapy, AdjuvantClinical Trials, Phase III as TopicDisease-Free SurvivalDouble-Blind MethodFemaleFollow-Up StudiesHumansMastectomyMiddle AgedMulticenter Studies as TopicNeoadjuvant TherapyNeoplasm Recurrence, LocalNeoplasm, ResidualOxazolesPlacebosProspective StudiesPyridinesQuinazolinesRandomized Controlled Trials as TopicReceptor, ErbB-2ConceptsInvasive disease-free survivalDisease-free survivalBrain metastasis-free survivalBreast cancer-free survivalDistant recurrence-free survivalT-DM1Overall survivalResidual diseaseHER2-positive invasive breast cancerAdjuvant T-DM1Cancer-free survivalRecurrence-free survivalInvasive breast cancerMetastasis-free survivalPharmacokinetic end pointsOutcomes of interestQuality of lifeEligible patientsAdjuvant radiotherapyEndocrine therapyNeoadjuvant chemotherapyCorrelative biomarkersCare guidelinesBreast cancerPlaceboAdjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up
Piccart M, Procter M, Fumagalli D, de Azambuja E, Clark E, Ewer MS, Restuccia E, Jerusalem G, Dent S, Reaby L, Bonnefoi H, Krop I, Liu TW, Pieńkowski T, Toi M, Wilcken N, Andersson M, Im YH, Tseng LM, Lueck HJ, Colleoni M, Monturus E, Sicoe M, Guillaume S, Bines J, Gelber RD, Viale G, Thomssen C. Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer in the APHINITY Trial: 6 Years' Follow-Up. Journal Of Clinical Oncology 2021, 39: 1448-1457. PMID: 33539215, DOI: 10.1200/jco.20.01204.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalBreast cancerHazard ratioOverall survivalHigh-risk node-negative breast cancerEarly HER2-positive breast cancerHER2-positive early breast cancerNode-negative breast cancerHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2HR-negative diseaseHR-positive diseaseInterim overall survivalNode-negative cohortNode-positive cohortPrimary cardiac eventsSix-year OSStandard adjuvant chemotherapyDisease-free survivalNew safety signalsEarly breast cancerGrowth factor receptor 2Standard adjuvant therapyPositive breast cancer
2020
A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer
Krop I, Abramson V, Colleoni M, Traina T, Holmes F, Garcia-Estevez L, Hart L, Awada A, Zamagni C, Morris PG, Schwartzberg L, Chan S, Gucalp A, Biganzoli L, Steinberg J, Sica L, Trudeau M, Markova D, Tarazi J, Zhu Z, O'Brien T, Kelly C, Winer E, Yardley D. A Randomized Placebo Controlled Phase II Trial Evaluating Exemestane with or without Enzalutamide in Patients with Hormone Receptor–Positive Breast Cancer. Clinical Cancer Research 2020, 26: 6149-6157. PMID: 32988969, DOI: 10.1158/1078-0432.ccr-20-1693.Peer-Reviewed Original ResearchConceptsProgression-free survivalHormone receptor-positive breast cancerReceptor-positive breast cancerPhase II trialEndocrine therapyBreast cancerII trialAR mRNACohort 1Higher AR mRNA levelsLower ESR1 mRNA levelsET-naïve patientsGrade adverse eventsPrior endocrine therapyMetastatic breast cancerAndrogen receptor inhibitorMRNA levelsAR mRNA levelsESR1 mRNA levelsEnzalutamide armITT populationTreat populationAdvanced diseasePrimary endpointAdverse eventsTumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer
Barroso-Sousa R, Keenan TE, Pernas S, Exman P, Jain E, Garrido-Castro AC, Hughes M, Bychkovsky B, Umeton R, Files JL, Lindeman NI, MacConaill LE, Hodi FS, Krop IE, Dillon D, Winer EP, Wagle N, Lin NU, Mittendorf EA, Van Allen EM, Tolaney SM. Tumor Mutational Burden and PTEN Alterations as Molecular Correlates of Response to PD-1/L1 Blockade in Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2020, 26: 2565-2572. PMID: 32019858, PMCID: PMC7269810, DOI: 10.1158/1078-0432.ccr-19-3507.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerHigh tumor mutational burdenProgression-free survivalTumor mutational burdenObjective response rateImmune checkpoint inhibitorsAnti-PD-1/L1 therapyTriple-negative breast cancerOverall survivalL1 therapyPD-L1Breast cancerMutational burdenLow objective response rateLonger progression-free survivalShorter progression-free survivalDana-Farber Cancer InstituteTumor genomic featuresShorter overall survivalMutations/megabaseCheckpoint inhibitorsVisceral metastasesL1 blockadePerformance statusPrior linesSensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer
Parsons HA, Rhoades J, Reed SC, Gydush G, Ram P, Exman P, Xiong K, Lo CC, Li T, Fleharty M, Kirkner GJ, Rotem D, Cohen O, Yu F, Fitarelli-Kiehl M, Leong KW, Hughes ME, Rosenberg SM, Collins LC, Miller KD, Blumenstiel B, Trippa L, Cibulskis C, Neuberg DS, DeFelice M, Freeman SS, Lennon NJ, Wagle N, Ha G, Stover DG, Choudhury AD, Getz G, Winer EP, Meyerson M, Lin NU, Krop I, Love JC, Makrigiorgos GM, Partridge AH, Mayer EL, Golub TR, Adalsteinsson VA. Sensitive Detection of Minimal Residual Disease in Patients Treated for Early-Stage Breast Cancer. Clinical Cancer Research 2020, 26: 2556-2564. PMID: 32170028, PMCID: PMC7654718, DOI: 10.1158/1078-0432.ccr-19-3005.Peer-Reviewed Original ResearchConceptsMinimal residual diseaseMetastatic breast cancerDigital droplet PCRBreast cancerTumor mutationsResidual diseaseMRD detectionEarly-stage breast cancerCurative-intent treatmentCohort of patientsEarly-stage diseaseMedian lead timeClinical data collectionWhole-exome sequencingMRD testFirst positive sampleDistant recurrenceMost patientsMetastatic diagnosisStage 0PatientsPlasma samplingClinical sensitivityPatient-specific mutationsCfDNA samples
2019
A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer
Veeraraghavan J, De Angelis C, Mao R, Wang T, Herrera S, Pavlick AC, Contreras A, Nuciforo P, Mayer IA, Forero A, Nanda R, Goetz MP, Chang JC, Wolff AC, Krop IE, Fuqua SAW, Prat A, Hilsenbeck SG, Weigelt B, Reis-Filho JS, Gutierrez C, Osborne CK, Rimawi MF, Schiff R. A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer. Annals Of Oncology 2019, 30: 927-933. PMID: 30903140, PMCID: PMC6594453, DOI: 10.1093/annonc/mdz076.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesFemaleFollow-Up StudiesGene AmplificationHumansIn Situ Hybridization, FluorescenceLapatinibNeoadjuvant TherapyPhosphatidylinositol 3-KinasesPrognosisReceptor, ErbB-2Remission InductionTrastuzumabConceptsPathologic complete responsePI3K pathway statusBreast cancerHER2 ratioPI3K pathwayNeoadjuvant lapatinibComplete responseHER2 amplificationPathway statusHER2-positive breast cancerPI3K pathway alterationsHER2 amplification levelHER2 FISH ratioK pathwayAnti-HER2 therapyWild-type PIK3CAPI3K pathway activationPIK3CA mutationsClinical subtypesHER2 overexpressionFISH ratioPatientsChemotherapyHER2High PTENTrastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study
Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2-positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. The Lancet Oncology 2019, 20: 816-826. PMID: 31047803, DOI: 10.1016/s1470-2045(19)30097-x.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsCamptothecinFemaleFollow-Up StudiesHumansImmunoconjugatesMaximum Tolerated DoseMiddle AgedPrognosisReceptor, ErbB-2Salvage TherapySurvival RateTissue DistributionTrastuzumabConceptsHER2-positive breast cancerTreatment-emergent adverse eventsAdvanced-stage breast cancerTrastuzumab emtansine treatmentTrastuzumab deruxtecanPhase 1 trialBreast cancerAdverse eventsProgressive diseaseSerious treatment-emergent adverse eventsWorse treatment-emergent adverse eventsAdvanced HER2-positive breast cancerSolid tumorsTopoisomerase I inhibitor payloadFrequent grade 3Grade 3 eventsTreatment-related deathsManageable safety profileAdvanced solid tumorsMultiple-dose studyPhase 1 studyInterstitial lung diseaseWithdrawal of consentWhite blood cellsYears of ageSeven-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
Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial
Krop IE, Mayer IA, Ganju V, Dickler M, Johnston S, Morales S, Yardley DA, Melichar B, Forero-Torres A, Lee SC, de Boer R, Petrakova K, Vallentin S, Perez EA, Piccart M, Ellis M, Winer E, Gendreau S, Derynck M, Lackner M, Levy G, Qiu J, He J, Schmid P. Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2016, 17: 811-821. PMID: 27155741, PMCID: PMC5524539, DOI: 10.1016/s1470-2045(16)00106-6.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overBiomarkers, TumorBreast NeoplasmsDouble-Blind MethodDrug Resistance, NeoplasmEstradiolEstrogen Receptor AntagonistsFemaleFollow-Up StudiesFulvestrantHumansMiddle AgedNeoplasm Recurrence, LocalNeoplasm StagingPrognosisReceptor, ErbB-2Receptors, EstrogenSalvage TherapySurvival RateConceptsProgression-free survivalSerious adverse eventsTreatment-related serious adverse eventsWorse adverse eventsPlacebo groupAdverse eventsNon-measurable diseaseAromatase inhibitor treatmentPIK3CA mutationsBreast cancerDay 1Grade 3Inhibitor treatmentDay 15Cycle 1Median progression-free survivalHER2-negative breast cancerEndocrine-resistant breast cancerPIK3CA-mutated tumorsPhase 2 studyPhase 2 trialMetastatic breast cancerWeeks of treatmentAromatase inhibitor resistanceF Hoffmann-La Roche
2015
Chemotherapy-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 regimensAmenorrheaTrastuzumabMonthsAdjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer
Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I, Wolff AC, Carey LA, Overmoyer BA, Partridge AH, Guo H, Hudis CA, Krop IE, Burstein HJ, Winer EP. Adjuvant Paclitaxel and Trastuzumab for Node-Negative, HER2-Positive Breast Cancer. New England Journal Of Medicine 2015, 372: 134-141. PMID: 25564897, PMCID: PMC4313867, DOI: 10.1056/nejmoa1406281.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleFollow-Up StudiesHumansInfusions, IntravenousMastectomy, SegmentalMiddle AgedNeoplasm Recurrence, LocalPaclitaxelRadiotherapyReceptor, ErbB-2Survival RateTrastuzumabConceptsHER2-positive breast cancerBreast cancerAdjuvant paclitaxelEjection fractionInvasive diseaseStage I HER2-positive breast cancerHuman epidermal growth factor receptor type 2Epidermal growth factor receptor type 2Symptomatic congestive heart failureHER2-negative breast cancerLeft ventricular ejection fractionDistant metastatic breast cancerFactor receptor type 2Discontinuation of trastuzumabGrade 3 neuropathySingle standard treatmentPrimary end pointCongestive heart failureMetastatic breast cancerVentricular ejection fractionPositive breast cancerInvestigator-initiated studyReceptor type 2Disease-specific eventsMedian follow
2013
Clinicopathological Features Among Patients With Advanced Human Epidermal Growth Factor–2-Positive Breast Cancer With Prolonged Clinical Benefit to First-Line Trastuzumab-Based Therapy: A Retrospective Cohort Study
Vaz-Luis I, Seah D, Olson EM, Wagle N, Metzger-Filho O, Sohl J, Litsas G, Burstein HJ, Krop IE, Winer EP, Lin NU. Clinicopathological Features Among Patients With Advanced Human Epidermal Growth Factor–2-Positive Breast Cancer With Prolonged Clinical Benefit to First-Line Trastuzumab-Based Therapy: A Retrospective Cohort Study. Clinical Breast Cancer 2013, 13: 254-263. PMID: 23829891, PMCID: PMC4084778, DOI: 10.1016/j.clbc.2013.02.010.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularChemotherapy, AdjuvantFemaleFollow-Up StudiesHumansMiddle AgedNeoplasm MetastasisNeoplasm Recurrence, LocalNeoplasm StagingPractice Patterns, Physicians'PrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesSurvival RateTamoxifenYoung AdultConceptsTrastuzumab-based therapyFirst-line trastuzumab-based therapyAdvanced HER2-positive breast cancerHER2-positive breast cancerAdjuvant trastuzumabBreast cancerClinicopathological featuresClinical benefitC-statisticHuman epidermal growth factor-2-positive breast cancerTreatment durationPredictive valueHormone receptor-positive tumorsLong-term clinical benefitPrevious adjuvant trastuzumabTreatment duration groupsRetrospective cohort studyDisease-free intervalHormone receptor positivityReceptor-positive tumorsDuration of treatmentMagnitude of benefitLow predictive valueLogistic regression modelsDifferent logistic regression models
2010
Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer
Krop IE, Beeram M, Modi S, Jones SF, Holden SN, Yu W, Girish S, Tibbitts J, Yi JH, Sliwkowski MX, Jacobson F, Lutzker SG, Burris HA. Phase I Study of Trastuzumab-DM1, an HER2 Antibody-Drug Conjugate, Given Every 3 Weeks to Patients With HER2-Positive Metastatic Breast Cancer. Journal Of Clinical Oncology 2010, 28: 2698-2704. PMID: 20421541, DOI: 10.1200/jco.2009.26.2071.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBiopsy, NeedleBone NeoplasmsBreast NeoplasmsDose-Response Relationship, DrugDrug Administration ScheduleFemaleFollow-Up StudiesHalf-LifeHumansImmunoconjugatesImmunohistochemistryLiver NeoplasmsLung NeoplasmsMaximum Tolerated DoseMaytansineMiddle AgedNeoplasm StagingPatient SelectionReceptor, ErbB-2Risk AssessmentSurvival AnalysisThrombocytopeniaTrastuzumabTreatment OutcomeConceptsMaximum-tolerated doseAdvanced HER2-positive breast cancerHER2-positive breast cancerTrastuzumab-DM1Breast cancerAdverse eventsCommon drug-related adverse eventsHER2-positive metastatic breast cancerDrug-related adverse eventsHER2 antibody-drug conjugatesClinical benefit rateConfirmed response rateSubstantial clinical activityTrastuzumab-based therapyMetastatic breast cancerHER2-positive cellsAntibody-drug conjugatesMeasurable diseaseNeuropathy eventsElevated transaminasesCardiac effectsDose modificationMetastatic diseaseObjective responseReversible toxicity