2023
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
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 ResearchConceptsHER2-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
Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis
Garcia-Recio S, Hinoue T, Wheeler G, Kelly B, Garrido-Castro A, Pascual T, De Cubas A, Xia Y, Felsheim B, McClure M, Rajkovic A, Karaesmen E, Smith M, Fan C, Ericsson P, Sanders M, Creighton C, Bowen J, Leraas K, Burns R, Coppens S, Wheless A, Rezk S, Garrett A, Parker J, Foy K, Shen H, Park B, Krop I, Anders C, Gastier-Foster J, Rimawi M, Nanda R, Lin N, Isaacs C, Marcom P, Storniolo A, Couch F, Chandran U, Davis M, Silverstein J, Ropelewski A, Liu M, Hilsenbeck S, Norton L, Richardson A, Symmans W, Wolff A, Davidson N, Carey L, Lee A, Balko J, Hoadley K, Laird P, Mardis E, King T, Perou C. Multiomics in primary and metastatic breast tumors from the AURORA US network finds microenvironment and epigenetic drivers of metastasis. Nature Cancer 2022, 4: 128-147. PMID: 36585450, PMCID: PMC9886551, DOI: 10.1038/s43018-022-00491-x.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerHER2-targeted therapiesImmune cell infiltratesMetastatic breast tumorsLiver metastasesCell infiltrateLow-pass whole-genome sequencingSubtype changesT cellsEstrogen receptorTumor subtypesEndothelial contentBreast tumorsMetastasisCell-cell adhesion genesReduced expressionGlobal DNA methylationDNA methylation mechanismsFocal deletionsMolecular featuresWhole-genome sequencingCancerSubtypesRNA sequencing
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 cancerPlacebo
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 MRIA Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer
Barroso-Sousa R, Krop IE, Trippa L, Tan-Wasielewski Z, Li T, Osmani W, Andrews C, Dillon D, Richardson ET, Pastorello RG, Winer EP, Mittendorf EA, Bellon JR, Schoenfeld JD, Tolaney SM. A Phase II Study of Pembrolizumab in Combination With Palliative Radiotherapy for Hormone Receptor-positive Metastatic Breast Cancer. Clinical Breast Cancer 2020, 20: 238-245. PMID: 32113750, DOI: 10.1016/j.clbc.2020.01.012.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreastBreast NeoplasmsCarcinoma, Ductal, BreastChemoradiotherapyDrug Administration ScheduleFemaleHumansInfusions, IntravenousMiddle AgedPalliative CareProgrammed Cell Death 1 ReceptorProgression-Free SurvivalReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneResponse Evaluation Criteria in Solid TumorsConceptsMetastatic breast cancerHormone receptor-positive metastatic breast cancerProgression-free survivalRadiation therapyObjective responseOverall survivalBreast cancerResponse rateMedian progression-free survivalCause adverse eventsGrade 3 eventsMedian prior linesMedian overall survivalObjective response ratePalliative radiation therapyPhase II studyTumor-infiltrating lymphocytesLymph node lesionsOverall response rateEpidermal growth factor receptorEligible patientsExploratory endpointsGrowth factor receptorPalliative radiotherapyPrimary endpoint
2019
Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022
Freedman RA, Gelman RS, Agar NYR, Santagata S, Randall EC, Lopez B, Connolly RM, Dunn IF, Van Poznak CH, Anders CK, Melisko ME, Silvestri K, Cotter CM, Componeschi KP, Marte JM, Moy B, Blackwell KL, Puhalla SL, Ibrahim N, Moynihan TJ, Nangia J, Tung N, Burns R, Rimawi MF, Krop IE, Wolff AC, Winer EP, Lin NU, Consortium T. Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022. Clinical Breast Cancer 2019, 20: 145-151.e2. PMID: 31558424, PMCID: PMC7035200, DOI: 10.1016/j.clbc.2019.07.011.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAdultAntineoplastic Combined Chemotherapy ProtocolsBrainBrain NeoplasmsBreastBreast NeoplasmsChemotherapy, AdjuvantCraniotomyDrug Administration ScheduleFemaleHumansMiddle AgedNeoadjuvant TherapyPilot ProjectsQuinolinesReceptor, ErbB-2Tissue DistributionTreatment OutcomeConceptsCentral nervous system penetrationCerebrospinal fluidBrain metastasesStudy treatmentDisease progressionHER2-positive breast cancer brain metastasesHER2-positive metastatic breast cancerHER2-positive brain metastasesBreast cancer brain metastasesGrade 3 diarrheaCancer brain metastasesMetastatic breast cancerCentral nervous systemResected tumor tissueBlood-based analysesNeratinib monotherapyPostoperative cyclesParenchymal tumorsStudy protocolBreast cancerTumor histopathologyPatientsNervous systemSmall cohortSurgical tissuesThe 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
4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4) † † These guidelines were developed by the European School of Oncology (ESO) and the European Society for Medical Oncology (ESMO).
Cardoso F, Senkus E, Costa A, Papadopoulos E, Aapro M, André F, Harbeck N, Lopez B, Barrios CH, Bergh J, Biganzoli L, Boers-Doets CB, Cardoso MJ, Carey LA, Cortés J, Curigliano G, Diéras V, Saghir N, Eniu A, Fallowfield L, Francis PA, Gelmon K, Johnston SRD, Kaufman B, Koppikar S, Krop IE, Mayer M, Nakigudde G, Offersen BV, Ohno S, Pagani O, Paluch-Shimon S, Penault-Llorca F, Prat A, Rugo HS, Sledge GW, Spence D, Thomssen C, Vorobiof DA, Xu B, Norton L, Winer EP. 4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4) † † These guidelines were developed by the European School of Oncology (ESO) and the European Society for Medical Oncology (ESMO). Annals Of Oncology 2018, 29: 1634-1657. PMID: 30032243, PMCID: PMC7360146, DOI: 10.1093/annonc/mdy192.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorBiopsy, Large-Core NeedleBreastBreast NeoplasmsChemoradiotherapy, AdjuvantClinical Trials as TopicConsensus Development Conferences as TopicEuropeEvidence-Based MedicineFemaleHumansIntegrative MedicineMastectomyMedical OncologyNeoadjuvant TherapyNeoplasm StagingSocieties, MedicalTreatment Outcome
2016
Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant
Spoerke JM, Gendreau S, Walter K, Qiu J, Wilson TR, Savage H, Aimi J, Derynck MK, Chen M, Chan IT, Amler LC, Hampton GM, Johnston S, Krop I, Schmid P, Lackner MR. Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant. Nature Communications 2016, 7: 11579. PMID: 27174596, PMCID: PMC4869259, DOI: 10.1038/ncomms11579.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreastBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDNA Mutational AnalysisDNA, NeoplasmDrug Resistance, NeoplasmEstradiolEstrogen Receptor alphaEstrogen Receptor AntagonistsEstrogensFemaleFulvestrantHumansIndazolesMiddle AgedMutationProtein Kinase InhibitorsSulfonamidesConceptsMetastatic breast cancer patientsESR1 mutationsBreast cancer patientsCancer patientsPan-PI3K inhibitorPIK3CA-mutated tumorsProgression-free survivalMetastatic breast cancerWild-type patientsClinical trial samplesMutation allele frequencyInhibitor therapyFulvestrant treatmentBreast cancerClinical significanceClinical resistancePatientsBaseline samplesHotspot mutationsK inhibitorsTherapyLongitudinal analysisTrial samplesESR1Distinct clones
2013
Prospective clinical experience with research biopsies in breast cancer patients
Vaz-Luis I, Zeghibe CA, Frank ES, Sohl J, Washington KE, Silverman SG, Fonte JM, Mayer EL, Overmoyer BA, Richardson AL, Krop IE, Winer EP, Lin NU. Prospective clinical experience with research biopsies in breast cancer patients. Breast Cancer Research And Treatment 2013, 142: 203-209. PMID: 24113744, PMCID: PMC3825285, DOI: 10.1007/s10549-013-2717-5.Peer-Reviewed Original ResearchConceptsResearch biopsiesAdverse eventsDisease courseMetastatic samplesDana-Farber Cancer InstituteGrade 2 painGrade 3 painProspective clinical experiencePatient's disease courseSingle institution experienceBreast cancer patientsPerformance of biopsyHigh rateAnalytic cohortFirst recurrenceMetastatic diseaseMost patientsPerformance statusReceptor statusPrimary cancerProspective studyCancer patientsBreast cancerPatientsBiopsy
2001
A SAGE (serial analysis of gene expression) view of breast tumor progression.
Porter DA, Krop IE, Nasser S, Sgroi D, Kaelin CM, Marks JR, Riggins G, Polyak K. A SAGE (serial analysis of gene expression) view of breast tumor progression. Cancer Research 2001, 61: 5697-702. PMID: 11479200.Peer-Reviewed Original ResearchConceptsGene expression profilesMammary epithelial cellsNormal mammary epithelial cellsExpression profilesGlobal gene expression profilesDistinct gene expression patternsSet of genesGene expression patternsConsistent phenotypic changesBreast tumorigenesisCarcinoma transitionEpithelial cellsSecreted proteinsSAGE librariesExpression patternsGene expressionPhenotypic changesGenesBreast tumor progressionMolecular levelSerial analysisSpecific stagesMammary epitheliumTumor progressionPromising targetHIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells
Krop I, Sgroi D, Porter D, Lunetta K, LeVangie R, Seth P, Kaelin C, Rhei E, Bosenberg M, Schnitt S, Marks J, Pagon Z, Belina D, Razumovic J, Polyak K. HIN-1, a putative cytokine highly expressed in normal but not cancerous mammary epithelial cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 9796-9801. PMID: 11481438, PMCID: PMC55532, DOI: 10.1073/pnas.171138398.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBlotting, NorthernBlotting, WesternBreastBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, Intraductal, NoninfiltratingCarcinoma, LobularCell DivisionCells, CulturedChlorocebus aethiopsCHO CellsCOS CellsCricetinaeCricetulusCytokinesDNA MethylationEpithelial CellsFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene LibraryGene SilencingGenes, Tumor SuppressorGrowth InhibitorsHumansMolecular Sequence DataNeoplasm ProteinsPromoter Regions, GeneticRecombinant Fusion ProteinsRNA, MessengerRNA, NeoplasmSequence AlignmentSequence Homology, Amino AcidTransfectionTumor Cells, CulturedTumor Suppressor ProteinsConceptsHIN-1 expressionHIN-1Mammary epithelial cellsPutative cytokineEpithelial cellsBreast cancer cell linesHuman breast carcinomaCancerous mammary epithelial cellsBreast cancer cellsCancer cell linesDuctal carcinomaLobular carcinomaPrimary tumorPreinvasive lesionsBreast carcinomaCandidate tumor suppressor geneMolecular alterationsTumor suppressor geneCarcinomaCancer cellsGene expression profilesCell linesCytokinesSuppressor geneCell growth