2023
ER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes
Chen J, Jacot W, Cortés J, Krop I, Dent S, Harbeck N, De Laurentiis M, Diéras V, Im Y, Stout T, Schimmoller F, Savage H, Hutchinson K, Wilson T. ER+, HER2− advanced breast cancer treated with taselisib and fulvestrant: genomic landscape and associated clinical outcomes. Molecular Oncology 2023, 17: 2000-2016. PMID: 36892268, PMCID: PMC10552898, DOI: 10.1002/1878-0261.13416.Peer-Reviewed Original ResearchConceptsProgression-free survivalBreast cancerShorter progression-free survivalNeurofibromin 1Advanced breast cancerBreast cancer patientsP53 pathway genesPI3K inhibitorsPI3K inhibitionBaseline ctDNAEndocrine therapyClinical outcomesCancer patientsEstrogen receptorCatalytic subunit alphaTumor DNATaselisibK inhibitorsK inhibitionPI3KOutcomesCancerAlterationsGenomic landscapeProtein p53
2021
Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients
Paoletti C, Regan MM, Niman SM, Dolce EM, Darga EP, Liu MC, Marcom PK, Hart LL, Smith JW, Tedesco KL, Amir E, Krop IE, DeMichele AM, Goodwin PJ, Block M, Aung K, Brown ME, McCormack RT, Hayes DF. Circulating tumor cell number and endocrine therapy index in ER positive metastatic breast cancer patients. Npj Breast Cancer 2021, 7: 77. PMID: 34117261, PMCID: PMC8196036, DOI: 10.1038/s41523-021-00281-1.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalER-positive metastatic breast cancerHER2-negative metastatic breast cancerWorse progression-free survivalWhole bloodTherapy indexExact testPositive metastatic breast cancer patientsMedian progression-free survivalMetastatic breast cancer patientsHuman epidermal growth factor receptorMulti-institutional clinical trialsGroup of patientsBreast cancer patientsSerial time pointsFisher's exact testTumor cell numberEpidermal growth factor receptorElevated CTCsGrowth factor receptorPrimary endpointClinical outcomesCancer patientsClinical trials
2020
Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer
Waks AG, Cohen O, Kochupurakkal B, Kim D, Dunn CE, Buendia J, Wander S, Helvie K, Lloyd MR, Marini L, Hughes ME, Freeman SS, Ivy SP, Geradts J, Isakoff S, LoRusso P, Adalsteinsson VA, Tolaney SM, Matulonis U, Krop IE, D’Andrea A, Winer EP, Lin NU, Shapiro GI, Wagle N. Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer. Annals Of Oncology 2020, 31: 590-598. PMID: 32245699, PMCID: PMC7946408, DOI: 10.1016/j.annonc.2020.02.008.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPlatinum chemotherapyDNA-damaging therapyMechanisms of resistanceBreast cancerMetastatic breast cancer patientsBreast cancer patientsTumor DNA sequencingNovel sequence alterationsWhole-exome sequencingDNA-damaging therapiesTreatment failureCancer patientsFunctional statusDisease progressionTumor biopsiesClinical cohortImmunohistochemical stainingSubsequent linesBRCA1/2 mutationsTherapeutic benefitPatientsUseful biomarkerFunctional assessmentTumor sections
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 Research
2017
264P Progression-free survival (PFS) and site of first progression in HER2+ metastatic breast cancer (MBC) patients (pts) with (w) or without (w/o) brain metastases: A pooled analysis of tucatinib phase I studies
Moulder S, Hamilton E, Ferrario C, Conlin A, Krop I, Chamberlain M, Gray T, Borges V. 264P Progression-free survival (PFS) and site of first progression in HER2+ metastatic breast cancer (MBC) patients (pts) with (w) or without (w/o) brain metastases: A pooled analysis of tucatinib phase I studies. Annals Of Oncology 2017, 28: v85. DOI: 10.1093/annonc/mdx365.027.Peer-Reviewed Original ResearchImmune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev).
Waks A, Barry W, Gjini E, Dillon D, Rodig S, Brock J, Baltay M, Savoie J, Stover D, Winer E, Krop I, Tolaney S. Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer (BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev). Journal Of Clinical Oncology 2017, 35: e12134-e12134. DOI: 10.1200/jco.2017.35.15_suppl.e12134.Peer-Reviewed Original ResearchTumor-infiltrating lymphocytesTPD-L1Miller-PaynePathologic responseImmune biomarkersHormone receptor-positive breast cancer patientsReceptor-positive breast cancer patientsPanCancer Immune Profiling PanelResidual cancer burden scorePathologic complete responsePD-L1 expressionBreast cancer patientsPD-L1 scoresImmune Profiling PanelImportant clinical implicationsPreoperative chemotherapyComplete responseProspective trialTumor-immune interactionsBurden scoreCancer patientsImmune microenvironmentUnadjusted analysesTumor gradeTreatment outcomes
2016
315TiP HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and T-DM1
Castan J, Verma S, Hurvitz S, Krop I, Tripathy D, Yardley D, Dionne M, Reynolds J, Wickham T, Molnar I, Miller K. 315TiP HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and T-DM1. Annals Of Oncology 2016, 27: vi99. DOI: 10.1093/annonc/mdw365.94.Peer-Reviewed Original ResearchHERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1).
Miller K, Cortes J, Hurvitz S, Krop I, Tripathy D, Verma S, Dionne M, Campbell K, Reynolds J, Wickham T, Molnar I, Yardley D. HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1). Journal Of Clinical Oncology 2016, 34: tps631-tps631. DOI: 10.1200/jco.2016.34.15_suppl.tps631.Peer-Reviewed Original ResearchHeterogeneity 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 clonesClinical trial enrollment expansion to the community.
Kostka J, Zerillo J, Kruse A, Sinclair N, Patrick M, McGovern L, Fuller F, O'Neil K, Hixon N, Weeks K, Johnson B, Krop I, Savoie J, Daftary F, Constantine M, Kaddis M, Rossi H, Tahir N, Norden A. Clinical trial enrollment expansion to the community. Journal Of Clinical Oncology 2016, 34: 112-112. DOI: 10.1200/jco.2016.34.7_suppl.112.Peer-Reviewed Original ResearchBreast cancer patientsClinical trial enrollmentClinical trialsEligible patientsTrial enrollmentCancer patientsNew breast cancer patientsNurse telephone callsProportion of patientsClinical trial programPre-screening patientsAcademic medical centerOncology patientsCancer practiceClinician visitsInitial consultationAcademic hospitalMedical CenterTrial discussionsPatientsTrial programClinical teamMultidisciplinary teamNumeric improvementsClinical staff
2015
Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients
Tolaney SM, Boucher Y, Duda DG, Martin JD, Seano G, Ancukiewicz M, Barry WT, Goel S, Lahdenrata J, Isakoff SJ, Yeh ED, Jain SR, Golshan M, Brock J, Snuderl M, Winer EP, Krop IE, Jain RK. Role of vascular density and normalization in response to neoadjuvant bevacizumab and chemotherapy in breast cancer patients. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 14325-14330. PMID: 26578779, PMCID: PMC4655544, DOI: 10.1073/pnas.1518808112.Peer-Reviewed Original ResearchConceptsPathologic complete responseBreast cancer patientsMicrovascular densityInterstitial fluid pressureNeoadjuvant bevacizumabBevacizumab monotherapyPathologic responseCancer patientsImproved pathologic responsePhase II studyPotential predictive biomarkersHER2-negative BCBasal-like subtypePreoperative bevacizumabPaclitaxel chemotherapyII studyComplete responseCombination therapyPredictive biomarkersPlasma biomarkersVascular normalizationBevacizumabVascular densityNew therapiesTissue biopsiesWhole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T).
Luis I, Oh C, Wang Z, Dipiro P, Macrae E, Painter C, Kryukov G, Krop I, Winer E, Lin N, Wagle N. Whole exome sequencing (WES) in HER2+ metastatic breast cancer (MBC) patients (pts) with extraordinary responses to trastuzumab (T). Journal Of Clinical Oncology 2015, 33: 611-611. DOI: 10.1200/jco.2015.33.15_suppl.611.Peer-Reviewed Original ResearchHERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1).
Miller K, Cortes J, Hurvitz S, Krop I, Tripathy D, Verma S, Riahi K, Reynolds J, Wickham T, Molnar I, Yardley D. HERMIONE: A Phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician’s choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1). Journal Of Clinical Oncology 2015, 33: tps641-tps641. DOI: 10.1200/jco.2015.33.15_suppl.tps641.Peer-Reviewed Original Research
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 cancerPatientsBiopsyDifferential changes in tissue biomarkers after bevacizumab (BEV) alone in a neoadjuvant study of BEV and chemotherapy in ER+ breast cancer (BC) versus triple-negative breast cancer (TNBC) patients (pts).
Boucher Y, Martin J, Tolaney S, Ancukiewicz M, Seano G, Goel S, Yeh E, Meyer J, Isakoff S, Duda D, Winer E, Krop I, Jain R. Differential changes in tissue biomarkers after bevacizumab (BEV) alone in a neoadjuvant study of BEV and chemotherapy in ER+ breast cancer (BC) versus triple-negative breast cancer (TNBC) patients (pts). Journal Of Clinical Oncology 2013, 31: 1065-1065. DOI: 10.1200/jco.2013.31.15_suppl.1065.Peer-Reviewed Original ResearchMean microvascular densityBreast cancerTissue biomarkersAnti-VEGF antibody bevacizumabTriple-negative breast cancer patientsMP scoresHigher pericyte coveragePhase II studyBreast cancer patientsEffectiveness of chemotherapyActivity of bevacizumabNeoadjuvant bevacizumabNeoadjuvant studiesPrimary endpointII studyPathologic responseBEV treatmentBC subtypesVascular functionAntibody bevacizumabCancer patientsMicrovascular densityPericyte coverageBevacizumabChemotherapyPrevalence of germline TP53 mutations in HER2+ breast cancer patients
Rath MG, Masciari S, Gelman R, Miron A, Miron P, Foley K, Richardson AL, Krop IE, Verselis SJ, Dillon DA, Garber JE. Prevalence of germline TP53 mutations in HER2+ breast cancer patients. Breast Cancer Research And Treatment 2013, 139: 193-198. PMID: 23580068, PMCID: PMC4280061, DOI: 10.1007/s10549-012-2375-z.Peer-Reviewed Original ResearchConceptsGermline TP53 mutationsLi-Fraumeni syndromeBreast cancer ageBreast cancerTP53 mutationsCancer ageER/PR statusYoung womenGermline TP53 mutation carriersGermline TP53 testingUnselected young womenTP53 mutation carriersBreast cancer patientsCohort of womenFamily cancer historyPotential clinical impactTP53 carriersTP53 testingPR statusSingle centerFrequent tumorsCancer historyCancer patientsChompret criteriaMultiplex ligation-dependent probe amplification (MLPA) technique
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 exposureHER2DoseTrialsE6. Can an international consensus meeting change the future of advanced breast cancer patients? Highlights from ABC1 Consensus Meeting
Cardoso F, Winer E, Norton L, Gomis R, Krop I, Harbeck N, Costa A. E6. Can an international consensus meeting change the future of advanced breast cancer patients? Highlights from ABC1 Consensus Meeting. European Journal Of Cancer 2012, 48: s13-s14. DOI: 10.1016/s0959-8049(12)70057-6.Peer-Reviewed Original Research
2011
P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer.
Sprecher E, Lezon-Geyda K, Sarkar S, Bossuyt V, Narayaan M, Kumar A, Krop I, Winer E, Tuck D, Kleinstein S, Harris L. P1-06-23: Changes in Gene Expression after One Dose of Trastuzumab (T) in HER2+ Breast Cancer Cell Lines Predict Novel Pathways of Response in HER2 Positive Early Stage Breast Cancer. Cancer Research 2011, 71: p1-06-23-p1-06-23. DOI: 10.1158/0008-5472.sabcs11-p1-06-23.Peer-Reviewed Original ResearchPathologic complete responseBreast cancer patientsBreast cancer cell linesSensitive cell linesCancer cell linesCancer patientsSingle doseBreast cancerHER2-positive early-stage breast cancerPositive early-stage breast cancerCell linesBreast tumorsEarly breast cancer patientsEarly-stage breast cancerDose of trastuzumabEarly-stage HER2Early breast cancerResistant breast tumorsStage breast cancerTumor core biopsiesPathway analysisMechanism of actionResistant HER2RECIST criteriaClinical responseAssociation between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors
Sprecher E, Sarkar S, Kleinstein S, Narayan M, Winer E, Tuck D, Lezon-Geyda K, Krop I, Harris L. Association between response to brief trastuzumab exposure in cell lines and early stage HER2+ breast tumors. 2011, 446-450. DOI: 10.1145/2147805.2147867.Peer-Reviewed Original ResearchEarly-stage HER2Breast cancer patientsBreast tumorsTrastuzumab treatmentCancer patientsCell linesHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Breast cancer settingGrowth factor receptor 2Resistant breast tumorsTrastuzumab-resistant HER2Breast cancer cell linesClinical treatment decisionsFactor receptor 2Trastuzumab exposureCancer cell linesGene expression signaturesResponsive patientsTrastuzumab resistanceSingle doseTargeted therapyBreast cancerCancer settingTreatment decisions