2024
TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer
Lynce F, Stevens L, Li Z, Brock J, Gulvady A, Huang Y, Nakhlis F, Patel A, Force J, Haddad T, Ueno N, Stearns V, Wolff A, Clark A, Bellon J, Richardson E, Balko J, Krop I, Winer E, Lange P, Hwang E, King T, Tolaney S, Thompson A, Gupta G, Mittendorf E, Regan M, Overmoyer B, Polyak K. TBCRC 039: a phase II study of preoperative ruxolitinib with or without paclitaxel for triple-negative inflammatory breast cancer. Breast Cancer Research 2024, 26: 20. PMID: 38297352, PMCID: PMC10829369, DOI: 10.1186/s13058-024-01774-0.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsFemaleHumansInflammatory Breast NeoplasmsInterleukin-6Neoadjuvant TherapyNitrilesPaclitaxelPyrazolesPyrimidinesTreatment OutcomeTriple Negative Breast NeoplasmsConceptsInflammatory breast cancerPathological complete responseTriple-negative IBCPhase II studyTN-IBCIL-6/JAK/STAT3 signalingBreast cancerRandomized phase II studyRun-inInvestigation of novel therapiesDoxorubicin plus cyclophosphamideTreatment naive patientsImmune suppressive effectsGrowth inhibitory effectNeoadjuvant therapyPreoperative therapyComplete responsePhosphorylated STAT3Tumor biopsiesWorse survivalII studyPrimary endpointSecondary endpointsImmune suppressionT cells
2023
Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030 ☆
Parsons H, Blewett T, Chu X, Sridhar S, Santos K, Xiong K, Abramson V, Patel A, Cheng J, Brufsky A, Rhoades J, Force J, Liu R, Traina T, Carey L, Rimawi M, Miller K, Stearns V, Specht J, Falkson C, Burstein H, Wolff A, Winer E, Tayob N, Krop I, Makrigiorgos G, Golub T, Mayer E, Adalsteinsson V. Circulating tumor DNA association with residual cancer burden after neoadjuvant chemotherapy in triple-negative breast cancer in TBCRC 030 ☆. Annals Of Oncology 2023, 34: 899-906. PMID: 37597579, PMCID: PMC10898256, DOI: 10.1016/j.annonc.2023.08.004.Peer-Reviewed Original ResearchMeSH KeywordsBreast NeoplasmsCirculating Tumor DNAFemaleHumansNeoadjuvant TherapyNeoplasm Recurrence, LocalNeoplasm, ResidualProspective StudiesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerResidual cancer burdenNeoadjuvant chemotherapyCancer burdenBreast cancerWeek 3Additional neoadjuvant chemotherapyPlasma samplesCase-control analysisCtDNA clearanceCtDNA positivityNeoadjuvant paclitaxelDisease recurrenceProspective studyWeek 12RCB 0CtDNA assaysPatientsSufficient tissueChemotherapyTumor fractionTumor DNARCB-3RespondersAdditional studies
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 ResearchMeSH KeywordsAnimalsBreastDNA MethylationEpigenesis, GeneticFemaleHumansMammary Neoplasms, AnimalMultiomicsTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsMetastatic 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 sequencingNodal Positivity in Early-Stage Triple-Negative Breast Cancer: Implications for Preoperative Immunotherapy
Mittendorf EA, Kantor O, Weiss A, Richardson E, Garrido-Castro A, Portnow LH, Krop IE, Lin NU, Winer EP, Tolaney SM, King TA. Nodal Positivity in Early-Stage Triple-Negative Breast Cancer: Implications for Preoperative Immunotherapy. Annals Of Surgical Oncology 2022, 30: 100-106. PMID: 35941343, DOI: 10.1245/s10434-022-12357-8.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerNational Cancer DatabaseNormal clinical examinationAxillary ultrasoundNegative clinical examinationClinical examinationUpfront surgeryCT2 tumorsInstitutional databaseBreast cancerEarly-stage triple-negative breast cancerStage triple-negative breast cancerAddition of immunotherapyNodal positivity ratePathologic nodal statusNode-positive patientsEvent-free survivalNode-positive diseaseRisk-benefit ratioCT1-2N0NCDB cohortPreoperative immunotherapyResultsFor patientsPositive nodesPreoperative chemotherapyCirculating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer
Lipsyc-Sharf M, de Bruin EC, Santos K, McEwen R, Stetson D, Patel A, Kirkner GJ, Hughes ME, Tolaney SM, Partridge AH, Krop IE, Knape C, Feger U, Marsico G, Howarth K, Winer EP, Lin NU, Parsons HA. Circulating Tumor DNA and Late Recurrence in High-Risk Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Breast Cancer. Journal Of Clinical Oncology 2022, 40: 2408-2419. PMID: 35658506, PMCID: PMC9467679, DOI: 10.1200/jco.22.00908.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorCirculating Tumor DNAHumansMutationNeoplasm Recurrence, LocalNeoplasm, ResidualProspective StudiesReceptor, ErbB-2Triple Negative Breast NeoplasmsConceptsMinimal residual diseaseWhole-exome sequencingClinical recurrenceMetastatic recurrenceBreast cancerEarly-stage hormone receptor-positive breast cancerHormone receptor-positive breast cancerTumor tissueHigh-risk stage IIReceptor-positive breast cancerTumor DNAHuman epidermal growth factor receptorDistant metastatic recurrenceHormone receptor positiveMRD-positive patientsPlasma samplesTime of consentPrimary tumor tissuesSufficient tumor tissueEpidermal growth factor receptorAdjuvant settingGrowth factor receptorLocal recurrenceClinical outcomesDistant metastasis
2020
Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer
Garrido-Castro AC, Saura C, Barroso-Sousa R, Guo H, Ciruelos E, Bermejo B, Gavilá J, Serra V, Prat A, Paré L, Céliz P, Villagrasa P, Li Y, Savoie J, Xu Z, Arteaga CL, Krop IE, Solit DB, Mills GB, Cantley LC, Winer EP, Lin NU, Rodon J. Phase 2 study of buparlisib (BKM120), a pan-class I PI3K inhibitor, in patients with metastatic triple-negative breast cancer. Breast Cancer Research 2020, 22: 120. PMID: 33138866, PMCID: PMC7607628, DOI: 10.1186/s13058-020-01354-y.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAminopyridinesAntineoplastic Combined Chemotherapy ProtocolsClass I Phosphatidylinositol 3-KinasesDisease ProgressionFemaleHigh-Throughput Nucleotide SequencingHumansMiddle AgedMorpholinesNeoplasm MetastasisPatient SafetyProtein Kinase InhibitorsProteomicsResponse Evaluation Criteria in Solid TumorsSurvival RateTreatment OutcomeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerProgression-free survivalPan-class I PI3K inhibitorMetastatic triple-negative breast cancerStable diseasePhase 2 studyBreast cancerOverall survivalPI3K inhibitorsPI3K pathwayPartial responseComplete responseClinical benefitSingle-arm phase 2 studyTriple-negative metastatic breast cancerMedian progression-free survivalK inhibitorsClinical benefit rateEfficacy of buparlisibK pathwayFrequent adverse eventsMedian overall survivalPercent of patientsMetastatic breast cancerSubset of patientsChanges in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer
Axelrod ML, Nixon MJ, Gonzalez-Ericsson PI, Bergman RE, Pilkinton MA, McDonnell WJ, Sanchez V, Opalenik SR, Loi S, Zhou J, Mackay S, Rexer BN, Abramson VG, Jansen VM, Mallal S, Donaldson J, Tolaney SM, Krop IE, Garrido-Castro AC, Marotti JD, Shee K, Miller TW, Sanders ME, Mayer IA, Salgado R, Balko JM. Changes in Peripheral and Local Tumor Immunity after Neoadjuvant Chemotherapy Reshape Clinical Outcomes in Patients with Breast Cancer. Clinical Cancer Research 2020, 26: 5668-5681. PMID: 32826327, PMCID: PMC7642197, DOI: 10.1158/1078-0432.ccr-19-3685.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAlbuminsAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenCD8-Positive T-LymphocytesFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMiddle AgedNeoadjuvant TherapyNeoplasm ProteinsNeoplasm Recurrence, LocalPaclitaxelPrognosisProgrammed Cell Death 1 ReceptorProgression-Free SurvivalTreatment OutcomeTriple Negative Breast NeoplasmsTumor MicroenvironmentConceptsTriple-negative breast cancerTumor immune microenvironmentNeoadjuvant chemotherapyOverall survivalBreast cancerPeripheral bloodResidual diseaseMetastatic triple-negative breast cancerEffect of NACImproved long-term outcomesActive antitumor immunityLocal tumor immunityRole of chemotherapyT-cell signatureLong-term outcomesPeripheral T cellsMultiple immune-related genesImmune-related genesNab-paclitaxelImmunologic effectsMicrometastatic diseasePersistent diseaseAntitumor immunityTumor immunityClinical outcomesTBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker
Mayer EL, Abramson V, Jankowitz R, Falkson C, Marcom PK, Traina T, Carey L, Rimawi M, Specht J, Miller K, Stearns V, Tung N, Perou C, Richardson AL, Componeschi K, Trippa L, Tan-Wasielewski Z, Timms K, Krop I, Wolff AC, Winer EP. TBCRC 030: a phase II study of preoperative cisplatin versus paclitaxel in triple-negative breast cancer: evaluating the homologous recombination deficiency (HRD) biomarker. Annals Of Oncology 2020, 31: 1518-1525. PMID: 32798689, PMCID: PMC8437015, DOI: 10.1016/j.annonc.2020.08.2064.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkersCisplatinHomologous RecombinationHumansMutationNeoadjuvant TherapyPaclitaxelProspective StudiesTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerHomologous recombination deficiencyPhase II studyPathologic responsePreoperative cisplatinII studyBreast cancerProspective phase II studyEffective predictive biomarkersInadequate clinical responsePreoperative chemotherapy regimenSingle-agent cisplatinHomologous recombination deficiency biomarkersGermline BRCA1/2Preoperative paclitaxelChemotherapy regimenClinical responseCisplatin chemotherapyPredictive biomarkersAlternative chemotherapyPreoperative trialInadequate responseHRD scoreStage IBaseline tissueTumor 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 linesTBCRC 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 ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsCisplatinCyclophosphamideDoxorubicinFemaleHumansMiddle AgedNeoadjuvant TherapyTriple Negative Breast NeoplasmsYoung AdultConceptsHER2-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 response
2019
First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors
Garrido‐Laguna I, Krop I, Burris HA, Hamilton E, Braiteh F, Weise AM, Abu‐Khalaf M, Werner TL, Pirie‐Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First‐in‐human, phase I study of PF‐06647263, an anti‐EFNA4 calicheamicin antibody–drug conjugate, in patients with advanced solid tumors. International Journal Of Cancer 2019, 145: 1798-1808. PMID: 30680712, PMCID: PMC6875752, DOI: 10.1002/ijc.32154.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerAdvanced solid tumorsTumor responseSolid tumorsMetastatic triple-negative breast cancerPhase IPhase 2 doseAntitumor activityHuman xenograft tumor modelsAvailable standard therapiesDose-related mannerLimited antitumor activityXenograft tumor modelCommon AEsStable diseaseManageable safetyPartial responsePotent antitumor activityStandard therapyToxicity probability interval methodOvarian cancerBreast cancerPatientsRP2DTumor model
2018
Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer
Stover DG, Parsons HA, Ha G, Freeman SS, Barry WT, Guo H, Choudhury AD, Gydush G, Reed SC, Rhoades J, Rotem D, Hughes ME, Dillon DA, Partridge AH, Wagle N, Krop IE, Getz G, Golub TR, Love JC, Winer EP, Tolaney SM, Lin NU, Adalsteinsson VA. Association of Cell-Free DNA Tumor Fraction and Somatic Copy Number Alterations With Survival in Metastatic Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2018, 36: jco.2017.76.003. PMID: 29298117, PMCID: PMC5815405, DOI: 10.1200/jco.2017.76.0033.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPrimary triple-negative breast cancerTumor fractionSomatic copy number alterationsCell-free DNABreast cancerSingle tertiary care institutionCopy number alterationsRetrospective cohort studySpecific somatic copy number alterationsTertiary care institutionNovel therapeutic approachesNumber alterationsCfDNA tumor fractionMetastatic survivalPrior chemotherapyTNBC cohortMetastatic settingCohort studyOverall survivalCancer Genome AtlasClinicopathologic factorsWorse survivalPrimary tumor
2016
3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3)
Cardoso F, Costa A, Senkus E, Aapro M, André F, Barrios C, Bergh J, Bhattacharyya G, Biganzoli L, Cardoso M, Carey L, Corneliussen-James D, Curigliano G, Dieras V, Saghir N, Eniu A, Fallowfield L, Fenech D, Francis P, Gelmon K, Gennari A, Harbeck N, Hudis C, Kaufman B, Krop I, Mayer M, Meijer H, Mertz S, Ohno S, Pagani O, Papadopoulos E, Peccatori F, Pernault-Llorca F, Piccart M, Pierga J, Rugo H, Shockney L, Sledge G, Swain S, Thomssen C, Tutt A, Vorobiof D, Xu B, Norton L, Winer E. 3rd ESO–ESMO international consensus guidelines for Advanced Breast Cancer (ABC 3). The Breast 2016, 31: 244-259. PMID: 27927580, DOI: 10.1016/j.breast.2016.10.001.Peer-Reviewed Original ResearchResponse and resistance to BET bromodomain inhibitors in triple-negative breast cancer
Shu S, Lin CY, He HH, Witwicki RM, Tabassum DP, Roberts JM, Janiszewska M, Jin Huh S, Liang Y, Ryan J, Doherty E, Mohammed H, Guo H, Stover DG, Ekram MB, Peluffo G, Brown J, D’Santos C, Krop I, Dillon D, McKeown M, Ott C, Qi J, Ni M, Rao P, Duarte M, Wu S, Chiang C, Anders L, Young R, Winer E, Letai A, Barry W, Carroll J, Long H, Brown M, Shirley Liu X, Meyer C, Bradner J, Polyak K. Response and resistance to BET bromodomain inhibitors in triple-negative breast cancer. Nature 2016, 529: 413-417. PMID: 26735014, PMCID: PMC4854653, DOI: 10.1038/nature16508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAzepinesBinding, CompetitiveCasein Kinase IICell Cycle ProteinsCell Line, TumorCell ProliferationChromatinDrug Resistance, NeoplasmEpigenesis, GeneticFemaleGene Expression Regulation, NeoplasticGenome, HumanHumansMediator Complex Subunit 1MiceNuclear ProteinsPhosphorylationPhosphoserineProtein BindingProtein Phosphatase 2Protein Structure, TertiaryProteomicsTranscription FactorsTranscription, GeneticTriazolesTriple Negative Breast NeoplasmsXenograft Model Antitumor Assays
2015
Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer
Tolaney SM, Tan S, Guo H, Barry W, Van Allen E, Wagle N, Brock J, Larrabee K, Paweletz C, Ivanova E, Janne P, Overmoyer B, Wright JJ, Shapiro GI, Winer EP, Krop IE. Phase II study of tivantinib (ARQ 197) in patients with metastatic triple-negative breast cancer. Investigational New Drugs 2015, 33: 1108-1114. PMID: 26123926, PMCID: PMC4608248, DOI: 10.1007/s10637-015-0269-8.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerPhase 2 studyProgression-free survivalBreast cancerPartial responseSingle-arm phase 2 studyResults 22 patientsPhase II studyDaily oral dosingOverall response rateRecent preclinical dataMechanism of actionTivantinib monotherapyMetastatic settingAdverse eventsII studyMethods PatientsPrior linesPreclinical dataOral dosingTivantinibPatientsMET expressionResponse rate
2014
Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor
Lu G, Zhang Q, Huang Y, Song J, Tomaino R, Ehrenberger T, Lim E, Liu W, Bronson RT, Bowden M, Brock J, Krop IE, Dillon DA, Gygi SP, Mills GB, Richardson AL, Signoretti S, Yaffe MB, Kaelin WG. Phosphorylation of ETS1 by Src Family Kinases Prevents Its Recognition by the COP1 Tumor Suppressor. Cancer Cell 2014, 26: 222-234. PMID: 25117710, PMCID: PMC4169234, DOI: 10.1016/j.ccr.2014.06.026.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBinding SitesFemaleHCT116 CellsHEK293 CellsHumansMiceMice, Inbred NODMice, SCIDMolecular Sequence DataNeoplasm TransplantationPhosphorylationProtein BindingProto-Oncogene Protein c-ets-1Proto-Oncogene Protein c-ets-2Src-Family KinasesTriple Negative Breast NeoplasmsTumor BurdenUbiquitinationUbiquitin-Protein LigasesConceptsSrc family kinasesFamily kinasesTumor suppressorPhosphorylation of ETS1Ubiquitin ligase componentTumor suppressor proteinAnchorage-independent growthNeighboring tyrosine residueCOP1 substratesRegulatory phosphorylationSpecific serineThreonine residuesSrc familySuppressor proteinTyrosine residuesETS1Breast cancer cellsPhosphorylationCancer cellsNeoplastic growthKinaseSuppressorProteinOncoproteinResiduesSeeds and Soil: Unraveling the Role of Local Tumor Stroma in Distant Metastasis
Duda DG, Ancukiewicz M, Isakoff SJ, Krop IE, Jain RK. Seeds and Soil: Unraveling the Role of Local Tumor Stroma in Distant Metastasis. Journal Of The National Cancer Institute 2014, 106: dju187. PMID: 25082335, DOI: 10.1093/jnci/dju187.Peer-Reviewed Original Research