2024
Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022
Freedman R, Heiling H, Li T, Trapani D, Tayob N, Smith K, Davis R, Pereslete A, DeMeo M, Cotter C, Chen W, Parsons H, Santa-Maria C, Van Poznak C, Moy B, Brufsky A, Melisko M, O’Sullivan C, Ashai N, Rauf Y, Nangia J, Burns R, Savoie J, Wolff A, Winer E, Rimawi M, Krop I, Lin N. Neratinib and Ado-Trastuzumab-Emtansine for Pre-treated and Untreated HER2-positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium Trial 022. Annals Of Oncology 2024 PMID: 38977064, DOI: 10.1016/j.annonc.2024.07.245.Peer-Reviewed Original ResearchHER2-positive breast cancer brain metastasesBreast cancer brain metastasesT-DM1Ado-trastuzumab emtansineCentral nervous systemOverall survivalCNS objective response rateEfficacy of neratinibT-DM1 exposureObjective response rateCancer brain metastasesPhase II studyMedian OSRANO-BMBrain MetastasesSlow accrualIntracranial activityII studyPrimary endpointPreclinical dataCohort 4Response assessmentTreatment optionsNeratinibPatientsTBCRC 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 ResearchConceptsInflammatory 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
2022
Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.
Tsuji J, Li T, Grinshpun A, Coorens T, Russo D, Anderson L, Rees R, Nardone A, Patterson C, Lennon NJ, Cibulskis C, Leshchiner I, Tayob N, Tolaney SM, Tung N, McDonnell DP, Krop IE, Winer EP, Stewart C, Getz G, Jeselsohn R. Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer. Clinical Cancer Research 2022, 28: 5066-5078. PMID: 36215125, PMCID: PMC9722539, DOI: 10.1158/1078-0432.ccr-22-2305.Peer-Reviewed Original ResearchConceptsProgression-free survivalPhase Ib/II studyCombination of palbociclibBreast cancerWhole-exome sequencingESR1 mutationsII studyClinical efficacySafety profileHormone receptor-positive/HER2-negative advanced breast cancerAdvanced hormone receptor-positive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerThird-generation selective estrogen receptor modulatorMedian progression-free survivalEndocrine-resistant breast cancerReceptor-positive breast cancerShorter progression-free survivalSelective estrogen receptor modulatorsClinical benefit rateAcceptable safety profileAdvanced breast cancerEstrogen receptor modulatorsSelective ER degraderDNA whole-exome sequencingPhase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I
Krop IE, Jegede OA, Grilley-Olson JE, Lauring JD, Mitchell EP, Zwiebel JA, Gray RJ, Wang V, McShane LM, Rubinstein LV, Patton D, Williams PM, Hamilton SR, Kono SA, Ford JM, Garcia AA, Sui XD, Siegel RD, Slomovitz BM, Conley BA, Arteaga CL, Harris LN, O'Dwyer PJ, Chen AP, Flaherty KT. Phase II Study of Taselisib in PIK3CA-Mutated Solid Tumors Other Than Breast and Squamous Lung Cancer: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol I. JCO Precision Oncology 2022, 6: e2100424. PMID: 35138919, PMCID: PMC8865530, DOI: 10.1200/po.21.00424.Peer-Reviewed Original ResearchConceptsProgression-free survivalOverall survivalSix-month progression-free survivalSolid tumorsMedian progression-free survivalSix-month overall survivalEnd pointSquamous cell lung carcinomaNational Cancer Institute-Molecular AnalysisMedian overall survivalObjective response ratePhase II studyPrimary end pointSecondary end pointsCell lung carcinomaSquamous lung cancerMutant breast cancerCommon toxicitiesEligible patientsProtocol therapyUnacceptable toxicityII studyPartial responseAdvanced cancerClinical outcomes
2021
A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer
Balch SM, Vaz-Luis I, Li T, Tayob N, Jain E, Helvie K, Buendia-Buendia JE, Shannon E, Isakoff SJ, Tung NM, Krop IE, Lin NU, Wagle N, Freedman RA. A phase II study of efficacy, toxicity, and the potential impact of genomic alterations on response to eribulin mesylate in combination with trastuzumab and pertuzumab in women with human epidermal growth factor receptor 2 (HER2)+ metastatic breast cancer. Breast Cancer Research And Treatment 2021, 189: 411-423. PMID: 34302589, DOI: 10.1007/s10549-021-06329-x.Peer-Reviewed Original ResearchConceptsHuman epidermal growth factor receptor 2Objective response ratePhase II studyWhole-exome sequencingEribulin 1.4II studyTreatment landscapeCohort AEribulin mesylateDay 1Genomic alterationsMetastatic breast cancer settingEpidermal growth factor receptor 2More frequent alterationsBreast cancer settingModest clinical activityGrowth factor receptor 2Metastatic breast cancerResponse/resistanceFactor receptor 2Manageable toxicityPertuzumab exposurePrimary endpointSix patientsCohort B
2020
TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes.
Tung NM, Robson ME, Ventz S, Santa-Maria CA, Nanda R, Marcom PK, Shah PD, Ballinger TJ, Yang ES, Vinayak S, Melisko M, Brufsky A, DeMeo M, Jenkins C, Domchek S, D'Andrea A, Lin NU, Hughes ME, Carey LA, Wagle N, Wulf GM, Krop IE, Wolff AC, Winer EP, Garber JE. TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes. Journal Of Clinical Oncology 2020, 38: 4274-4282. PMID: 33119476, DOI: 10.1200/jco.20.02151.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerObjective response rateProgression-free survivalPoly (ADP-ribose) polymerase (PARP) inhibitorsPhase II studyBreast cancerMutation carriersII studyMedian progression-free survivalNegative metastatic breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Clinical benefit rateHER2-negative diseasePlatinum-refractory diseaseGrowth factor receptor 2Population of patientsFactor receptor 2Homologous recombination-related genesConfirmed responsesEligible patientsMeasurable diseaseSecondary endpointsChemotherapy regimensPrimary endpointTBCRC 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 ResearchConceptsTriple-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 tissueTBCRC 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 ResearchConceptsHER2-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
2018
Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer
Dickler MN, Saura C, Richards DA, Krop IE, Cervantes A, Bedard PL, Patel MR, Pusztai L, Oliveira M, Cardenas AK, Cui N, Wilson TR, Stout TJ, Wei MC, Hsu JY, Baselga J. Phase II Study of Taselisib (GDC-0032) in Combination with Fulvestrant in Patients with HER2-Negative, Hormone Receptor–Positive Advanced Breast Cancer. Clinical Cancer Research 2018, 24: 4380-4387. PMID: 29793946, PMCID: PMC6139036, DOI: 10.1158/1078-0432.ccr-18-0613.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDisease-Free SurvivalDrug-Related Side Effects and Adverse ReactionsFemaleFulvestrantHumansImidazolesMiddle AgedMutationOxazepinesReceptor, ErbB-2Receptors, EstrogenConceptsAdverse eventsClinical activityBreast cancerMutation statusOpen-label phase II studyHR-positive breast cancerHigher objective response rateConfirmatory phase III trialNCI CTCAE v4.0Median treatment durationObjective response ratePhase II studySerious adverse eventsNew safety signalsPhase III trialsPositive breast cancerClin Cancer ResIntramuscular fulvestrantMeasurable diseaseRECIST v1.1II studyIII trialsPostmenopausal womenUnacceptable toxicityTumor responseA phase II study of atezolizumab (Atezo) combined with pertuzumab (P) and high-dose trastuzumab (H) for the treatment of central nervous system (CNS) metastases in patients with Her2-positive (HER2+) metastatic breast cancer (MBC).
Barroso-Sousa R, Barry W, Kumthekar P, Guo H, Silvestri K, Krop I, Winer E, Tolaney S, Lin N. A phase II study of atezolizumab (Atezo) combined with pertuzumab (P) and high-dose trastuzumab (H) for the treatment of central nervous system (CNS) metastases in patients with Her2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2018, 36: tps1100-tps1100. DOI: 10.1200/jco.2018.36.15_suppl.tps1100.Peer-Reviewed Original Research
2017
A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC).
Luis I, Guo H, Barry W, Krop I, Wagle N, Lowe A, Gore D, Andrews C, Osmani W, Isakoff S, Tung N, Winer E, Lin N, Freedman R. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC). Journal Of Clinical Oncology 2017, 35: 1034-1034. DOI: 10.1200/jco.2017.35.15_suppl.1034.Peer-Reviewed Original ResearchMetastatic breast cancerOverall response ratePhase II studyStable diseasePertuzumab exposureAdverse eventsII studyCohort AHuman epidermal growth factor receptorActivity of eribulinDose of eribulinFrequent grade 3First-line settingMost adverse eventsAnti-HER2 therapyCorrelative studiesEpidermal growth factor receptorCell-free DNAGrowth factor receptorHematologic toxicityCohort studyOverall survivalPartial responseCohort BSingle centerSeven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC).
Tolaney S, Barry W, Guo H, Dillon D, Dang C, Yardley D, Moy B, Marcom P, Albain K, Rugo H, Ellis M, Shapira I, Wolff A, Carey L, Overmoyer B, Partridge A, Hudis C, Krop I, Burstein H, Winer E. Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative, HER2-positive breast cancer (BC). Journal Of Clinical Oncology 2017, 35: 511-511. DOI: 10.1200/jco.2017.35.15_suppl.511.Peer-Reviewed Original ResearchBreast cancer-specific survivalDisease-free survivalRecurrence-free intervalBreast cancerDistant recurrenceOverall survivalTumor sizeNew contralateral breast cancerHER2-positive breast cancerNode-negative HER2Cancer-specific survivalPhase II studyContralateral breast cancerAdjuvant paclitaxelAPT trialNodal micrometastasisPrimary endpointProtocol therapyAdjuvant therapyDFS eventsII studyDisease recurrenceRegional recurrenceSpecific survivalClinical outcomes
2016
A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC).
Dickler M, Saura C, Richards D, Krop I, Cervantes A, Bedard P, Patel M, Pusztai L, Oliveira M, Ware J, Jin H, Wilson T, Stout T, Wei M, Hsu J, Baselga J. A phase II study of the PI3K inhibitor taselisib (GDC-0032) combined with fulvestrant (F) in patients (pts) with HER2-negative (HER2-), hormone receptor-positive (HR+) advanced breast cancer (BC). Journal Of Clinical Oncology 2016, 34: 520-520. DOI: 10.1200/jco.2016.34.15_suppl.520.Peer-Reviewed Original Research
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 biopsiesPhase 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
Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer
Tolaney S, Burris H, Gartner E, Mayer IA, Saura C, Maurer M, Ciruelos E, Garcia AA, Campana F, Wu B, Xu Y, Jiang J, Winer E, Krop I. Phase I/II study of pilaralisib (SAR245408) in combination with trastuzumab or trastuzumab plus paclitaxel in trastuzumab-refractory HER2-positive metastatic breast cancer. Breast Cancer Research And Treatment 2014, 149: 151-161. PMID: 25537644, DOI: 10.1007/s10549-014-3248-4.Peer-Reviewed Original ResearchConceptsHER2-positive metastatic breast cancerMetastatic breast cancerAdverse eventsBreast cancerArm 2Arm 1Phase I/II dose-escalation studyMetastatic HER2-positive breast cancerPhase I/II studyTreatment-related adverse eventsHER2-positive breast cancerTreatment-related gradeAcceptable safety profileDose-escalation studyDose-limiting toxicityDose-escalation designPan-class IEvaluable patientsPaclitaxel armPrior taxanePrior trastuzumabErythematous rashII studyPartial responsePeripheral neuropathyNI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION
Emblem K, Pinho M, Chandra V, Gerstner E, Stufflebeam S, Sorenson G, Harris G, Freedman R, Sohl J, Younger J, Krop I, Winer E, Lin N. NI-23BRAIN BREAST METASTASES RESPOND TO ANTI-ANGIOGENIC THERAPY BY MODES OF VASCULAR NORMALIZATION. Neuro-Oncology 2014, 16: v143-v143. PMCID: PMC4218348, DOI: 10.1093/neuonc/nou264.22.Peer-Reviewed Original ResearchAnti-angiogenic therapyBreast cancerBrain metastasesVascular normalizationTumor perfusionBrain tumorsDay 1Largest contrast-enhancing lesionPerfusion MRIParenchymal brain metastasesMonths of therapyPhase II studyHormone receptor statusMetastatic breast cancerSubset of patientsContrast-enhancing lesionsPrimary brain tumorsAnti-angiogenic effectsOxygen saturation levelsPrior therapyBreast metastasisII studySystemic therapyImproved survivalReceptor statusA phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with metastatic, human epidermal growth factor receptor 2-positive breast cancer.
Freedman R, Luis I, Barry W, Krop I, Wagle N, Lowe A, Galler S, Sohl J, Isakoff S, Tung N, Winer E, Lin N. A phase II study of eribulin mesylate in combination with trastuzumab and pertuzumab in patients (pts) with metastatic, human epidermal growth factor receptor 2-positive breast cancer. Journal Of Clinical Oncology 2014, 32: tps668-tps668. DOI: 10.1200/jco.2014.32.15_suppl.tps668.Peer-Reviewed Original ResearchTrastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer
Krop I, Winer EP. Trastuzumab Emtansine: A Novel Antibody–Drug Conjugate for HER2-Positive Breast Cancer. Clinical Cancer Research 2014, 20: 15-20. PMID: 24135146, DOI: 10.1158/1078-0432.ccr-13-0541.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerT-DM1Breast cancerAntibody-drug conjugatesAntibody-dependent cell-mediated cytotoxicityRecent phase III trialsHER2-positive breast cancerNovel antibody-drug conjugateCapecitabine/lapatinibFirst-line settingHepatic transaminase elevationsCombination of trastuzumabPhase II studyProgression-free survivalPhase III trialsInhibition of HER2Cell-mediated cytotoxicityFavorable toxicity profileHER2-positive tumor cellsMonoclonal antibody trastuzumabTransaminase elevationII studyIII trialsOverall survivalAdverse events
2013
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).
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 coverageBevacizumabChemotherapy