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
2018
286PD Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients
Specht J, Pusztai L, Forero-Torres A, Mita M, Weise A, Krop I, Grosse-Wilde A, Wang Z, Li M, Hengel S, Garfin P, Means G, Onsum M, Modi S. 286PD Post-treatment biopsies show evidence of cell cycle arrest and immune cell infiltration into tumors of ladiratuzumab vedotin-treated advanced breast cancer patients. Annals Of Oncology 2018, 29: viii92. DOI: 10.1093/annonc/mdy272.278.Peer-Reviewed Original ResearchThe tumor-immune microenvironment (TME) in HR+/HER2- metastatic breast cancer (mBC): Relationship to non-metastatic (met) tumors and prior treatment (tx) received.
Waks A, Tolaney S, Schnitt S, Dillon D, Gjini E, Abdelrahman S, Marino-Enriquez A, Helvie K, Marini L, Cohen O, Kim D, Wander S, Stover D, Rodig S, Krop I, Winer E, Lin N, Wagle N. The tumor-immune microenvironment (TME) in HR+/HER2- metastatic breast cancer (mBC): Relationship to non-metastatic (met) tumors and prior treatment (tx) received. Journal Of Clinical Oncology 2018, 36: 1054-1054. DOI: 10.1200/jco.2018.36.15_suppl.1054.Peer-Reviewed Original Research
2017
CDK4/6 inhibition triggers anti-tumour immunity
Goel S, DeCristo MJ, Watt AC, BrinJones H, Sceneay J, Li BB, Khan N, Ubellacker JM, Xie S, Metzger-Filho O, Hoog J, Ellis MJ, Ma CX, Ramm S, Krop IE, Winer EP, Roberts TM, Kim HJ, McAllister SS, Zhao JJ. CDK4/6 inhibition triggers anti-tumour immunity. Nature 2017, 548: 471-475. PMID: 28813415, PMCID: PMC5570667, DOI: 10.1038/nature23465.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigen PresentationBiological MimicryBreast NeoplasmsCell Cycle CheckpointsCell Line, TumorCell ProliferationCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalFemaleHumansInterferonsMicePhosphorylationProtein Kinase InhibitorsRepressor ProteinsRNA, Double-StrandedSignal TransductionT-Lymphocytes, RegulatoryTranscriptomeViruses64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer
Lee H, Shields AF, Siegel BA, Miller KD, Krop I, X. C, LoRusso PM, Munster PN, Campbell K, Gaddy DF, Leonard SC, Geretti E, Blocker SJ, Kirpotin DB, Moyo V, Wickham TJ, Hendriks BS. 64Cu-MM-302 Positron Emission Tomography Quantifies Variability of Enhanced Permeability and Retention of Nanoparticles in Relation to Treatment Response in Patients with Metastatic Breast Cancer. Clinical Cancer Research 2017, 23: 4190-4202. PMID: 28298546, PMCID: PMC6790129, DOI: 10.1158/1078-0432.ccr-16-3193.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedBone NeoplasmsBrain NeoplasmsBreast NeoplasmsCell Membrane PermeabilityCopper RadioisotopesCyclophosphamideDoxorubicinFemaleHumansLiverMiddle AgedNanoparticlesNeoplasm MetastasisPolyethylene GlycolsPositron Emission Tomography Computed TomographyReceptor, ErbB-2SpleenTrastuzumabConceptsPET/CTHER2-positive metastatic breast cancerMetastatic breast cancerFavorable treatment outcomesRetrospective exploratory analysisClin Cancer ResHuman metastatic tumorsEPR effectMetastatic tumorsClinical trialsPatient outcomesBrain lesionsTreatment outcomesBreast cancerClinical studiesDrug levelsPreclinical studiesTumor lesionsSolid tumorsPatientsBackground uptakeTherapeutic nanoparticlesCancer ResTumorsHuman tumorsPhase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors
Juric D, Krop I, Ramanathan RK, Wilson TR, Ware JA, Bohorquez S, Savage HM, Sampath D, Salphati L, Lin RS, Jin H, Parmar H, Hsu JY, Von Hoff DD, Baselga J. Phase I Dose-Escalation Study of Taselisib, an Oral PI3K Inhibitor, in Patients with Advanced Solid Tumors. Cancer Discovery 2017, 7: 704-715. PMID: 28331003, PMCID: PMC5501742, DOI: 10.1158/2159-8290.cd-16-1080.Peer-Reviewed Original ResearchConceptsDose-limiting toxicityAdverse eventsMutant tumorsHigh-grade adverse eventsTreatment-related adverse eventsConfirmed response rateMetastatic solid tumorsTumor xenograft modelPatient tumor samplesMeasurable diseasePharmacodynamic findingsPreclinical dataTumor patientsTumor growth inhibitorLow doseXenograft modelDose levelsResponse rateSolid tumorsPathway inhibitionPatientsPathway suppressionTumor samplesTumorsHotspot mutations
2016
313TiP SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumours
Baselga J, Castan J, De Laurentiis M, Dieras V, Harbeck N, Hsu J, Jin H, Schimmoller F, Wilson T, Im Y, Jacot W, Krop I, Verma S. 313TiP SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with oestrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA-mutant tumours. Annals Of Oncology 2016, 27: vi99. DOI: 10.1093/annonc/mdw365.92.Peer-Reviewed Original ResearchSANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors.
Baselga J, Cortes J, De Laurentiis M, Dieras V, Harbeck N, Hsu J, Ng V, Schimmoller F, Wilson T, Im Y, Jacot W, Krop I, Verma S. SANDPIPER: Phase III study of the PI3-kinase (PI3K) inhibitor taselisib (GDC-0032) plus fulvestrant in patients (pts) with estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer (BC) enriched for pts with PIK3CA- mutant tumors. Journal Of Clinical Oncology 2016, 34: tps617-tps617. DOI: 10.1200/jco.2016.34.15_suppl.tps617.Peer-Reviewed Original ResearchOvercoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors
Goel S, Wang Q, Watt AC, Tolaney SM, Dillon DA, Li W, Ramm S, Palmer AC, Yuzugullu H, Varadan V, Tuck D, Harris LN, Wong KK, Liu XS, Sicinski P, Winer EP, Krop IE, Zhao JJ. Overcoming Therapeutic Resistance in HER2-Positive Breast Cancers with CDK4/6 Inhibitors. Cancer Cell 2016, 29: 255-269. PMID: 26977878, PMCID: PMC4794996, DOI: 10.1016/j.ccell.2016.02.006.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCell Line, TumorCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Disease Models, AnimalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesNeoplasm Recurrence, LocalPhosphorylationProtein Kinase InhibitorsReceptor, ErbB-2TOR Serine-Threonine KinasesTumor Suppressor ProteinsConceptsHER2-positive breast cancerCDK4/6 inhibitorsBreast cancerEGFR/HER2Patient-derived xenograft tumorsTransgenic mouse modelInhibition of CDK4/6Tumor recurrenceXenograft tumorsMouse modelPotent suppressionTransgenic modelClinical specimensTherapeutic resistanceDual inhibitionMediate resistanceHER2CancerTSC2 phosphorylationG1 arrestCellular senescenceTherapyRb phosphorylationTumorsCDK4/6
2015
First-in-human dose escalation, safety, and PK study of a novel EFNA4-ADC in patients with advanced solid tumors.
Hong D, Garrido-Laguna I, Krop I, Subbiah V, Werner T, Cotter C, Hamilton E, Velastegui K, Xuan D, Bugarini R, Gollerkeri A, Burris H. First-in-human dose escalation, safety, and PK study of a novel EFNA4-ADC in patients with advanced solid tumors. Journal Of Clinical Oncology 2015, 33: 2520-2520. DOI: 10.1200/jco.2015.33.15_suppl.2520.Peer-Reviewed Original Research
2012
Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer.
Galanina N, Sprecher E, Bossuyt V, Sarkar S, Krop I, Winer E, Tuck D, Bruce C, Harris L. Evaluation of gene expression by RNA-seq after single dose of trastuzumab (T) reveals predictors of pathologic complete response (pCR) in HER2-positive early breast cancer. Journal Of Clinical Oncology 2012, 30: 10558-10558. DOI: 10.1200/jco.2012.30.15_suppl.10558.Peer-Reviewed Original ResearchPathologic complete responseSingle doseClinical trialsHER2-positive early breast cancerEarly breast cancer patientsEarly breast cancerBreast cancer patientsTumor core biopsiesSubsequent clinical trialsWeek time pointMost gene expression changesComplete responseCancer patientsPredictive markerCore biopsyBreast cancerImmune pathwaysTumorsTime pointsB2MGene expression changesBrief exposureHER2DoseTrials
2003
Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors.
Krop I, Maguire P, Lahti-Domenici J, Lodeiro G, Richardson A, Johannsdottir HK, Nevanlinna H, Borg A, Gelman R, Barkardottir RB, Lindblom A, Polyak K. Lack of HIN-1 methylation in BRCA1-linked and "BRCA1-like" breast tumors. Cancer Research 2003, 63: 2024-7. PMID: 12727813.Peer-Reviewed Original ResearchConceptsHIN-1 methylationBreast tumorsHIN-1BRCA1 tumorsSporadic breast tumorsFamilial breast cancer patientsBreast cancer patientsSpecific breast cancer subtypesBreast cancer riskBreast cancer subtypesSporadic breast carcinomasGerm-line mutationsPromoter methylation statusCancer patientsHER2 statusBreast carcinomaHistopathological phenotypeEstrogen receptorCancer riskCandidate tumor suppressor geneCancer subtypesSporadic casesTumorsCancer typesTumor suppressor gene