2014
Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer
Pusztai L, Moulder S, Altan M, Kwiatkowski D, Valero V, Ueno NT, Esteva FJ, Avritscher R, Qi Y, Strauss L, Hortobagyi GN, Hatzis C, Symmans WF. Gene Signature–Guided Dasatinib Therapy in Metastatic Breast Cancer. Clinical Cancer Research 2014, 20: 5265-5271. PMID: 25172932, DOI: 10.1158/1078-0432.ccr-14-0800.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerBreast cancerPredictive gene signaturesGene signatureClinical benefitBiopsy-related adverse eventsSingle-agent activityStable diseaseDasatinib therapyAdverse eventsUnderwent biopsyUnselected patientsPreclinical evidenceUnexpected toxicitiesThree-armPatientsSingle agentMolecular testingCLIA laboratoryDasatinib responseDasatinibBiopsyGene expression profilingCancerExpression profiling
2013
Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
James E, Chung G, Sowers N, Clark M, Lilian R, Abraham G, Chmael S, Cappiello M, DiGiovanna M, Hofstatter E, Sanft T, Israel G, Pusztai L, Harris L, Abu-Khalaf M. Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer. Journal Of Clinical Oncology 2013, 31: 154-154. DOI: 10.1200/jco.2013.31.26_suppl.154.Peer-Reviewed Original ResearchDose-expansion phaseGrade 3 non-hematological toxicityGrade 4 febrile neutropeniaCycle-1 DLTGrade 3 fatigueGrade 3/4 toxicitiesGrade 4 neutropeniaGrade 4 thrombocytopeniaMedian age 51Non-hematological toxicitiesObjective response rateAdvanced breast cancerDose-escalation phaseModest clinical activityHDAC inhibitor vorinostatClinical trial informationHistone deacetylase inhibitorsFebrile neutropeniaStable diseaseObjective responsePrior linesHematological toxicityTreatment delayClinical activityBreast cancerPhase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
James E, Chung G, DiGiovanna M, Sanft T, Hofstatter E, Sowers N, Clark M, Lilian R, Chmael S, Cappiello M, Abraham G, Israel G, Pusztai L, Harris L, Abu-Khalaf M. Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer. Journal Of Clinical Oncology 2013, 31: 2587-2587. DOI: 10.1200/jco.2013.31.15_suppl.2587.Peer-Reviewed Original ResearchDose-expansion phaseGrade 3 non-hematological toxicityTGFB pathwayGrade 4 febrile neutropeniaCycle-1 DLTGrade 3 fatigueGrade 3/4 toxicitiesGrade 4 neutropeniaGrade 4 thrombocytopeniaMedian age 51Non-hematological toxicitiesObjective response rateAdvanced breast cancerDose-escalation phaseModest clinical activityBiomarkers of responseHDAC inhibitor vorinostatClinical trial informationHistone deacetylase inhibitorsFebrile neutropeniaStable diseaseObjective responsePrior linesHematological toxicityTreatment delay
2010
Impact of Progression During Neoadjuvant Chemotherapy on Surgical Management of Breast Cancer
Caudle AS, Gonzalez-Angulo AM, Hunt KK, Pusztai L, Kuerer HM, Mittendorf EA, Hortobagyi GN, Meric-Bernstam F. Impact of Progression During Neoadjuvant Chemotherapy on Surgical Management of Breast Cancer. Annals Of Surgical Oncology 2010, 18: 932-938. PMID: 21061075, PMCID: PMC4347926, DOI: 10.1245/s10434-010-1390-8.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinoma, Ductal, BreastCarcinoma, LobularChemotherapy, AdjuvantCombined Modality TherapyFemaleFollow-Up StudiesHumansLymphatic MetastasisMastectomyMiddle AgedNeoadjuvant TherapyRetrospective StudiesSurvival RateTreatment OutcomeConceptsBreast conservation therapyNeoadjuvant chemotherapyBreast cancerSurgical managementDisease progressionStable diseaseImpact of progressionAdvanced breast cancerEarly-stage diseaseBCT candidatesClinical lymphadenopathyChemotherapy regimensProgressive diseaseStandard therapyComplete responseMedical oncologistsDistant metastasisClinicopathological dataFlap closurePatientsStage ITherapeutic interventionsOperative planEarly identificationMastectomyPredictors of Tumor Progression During Neoadjuvant Chemotherapy in Breast Cancer
Caudle AS, Gonzalez-Angulo AM, Hunt KK, Liu P, Pusztai L, Symmans WF, Kuerer HM, Mittendorf EA, Hortobagyi GN, Meric-Bernstam F. Predictors of Tumor Progression During Neoadjuvant Chemotherapy in Breast Cancer. Journal Of Clinical Oncology 2010, 28: 1821-1828. PMID: 20231683, PMCID: PMC2860366, DOI: 10.1200/jco.2009.25.3286.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsCarcinoma, Ductal, BreastCarcinoma, LobularChemotherapy, AdjuvantDisease ProgressionFemaleHumansMiddle AgedNeoadjuvant TherapyReceptors, EstrogenReceptors, ProgesteroneSurvival RateTaxoidsTreatment OutcomeYoung AdultConceptsHigh Ki-67 scoreNeoadjuvant chemotherapyKi-67 scoreStable diseaseBreast cancerEstrogen receptorMultivariate analysisDistant disease-free survivalER/PR negativityFirst-line surgical approachTumor progressionMost breast cancer patientsDisease-free survivalStandard neoadjuvant chemotherapyCancer clinical stageAmerican Joint CommitteeBreast cancer patientsAfrican American raceAdvanced tumor stagePredictors of responseHigh nuclear gradeHigh tumor gradeNegative estrogen receptorNovel molecular predictorsPR negativity
2009
Impact of Progression during Neoadjuvant Chemotherapy on Operative Management of Breast Cancer.
Caudle A, Gonzalez-Angulo A, Hunt K, Kuerer H, Pusztai L, Kau S, Mittendorf E, Hortobagyi G, Meric-Bernstam F. Impact of Progression during Neoadjuvant Chemotherapy on Operative Management of Breast Cancer. Cancer Research 2009, 69: 1090-1090. DOI: 10.1158/0008-5472.sabcs-09-1090.Peer-Reviewed Original ResearchBreast-conserving therapyNeoadjuvant chemotherapyStable diseaseFirst regimenOperative managementDisease progressionBreast cancerSecond regimenMulti-disciplinary team membersImpact of progressionSecond chemotherapy regimenAdvanced breast cancerEarly-stage diseaseStandard of careBCT candidatesClinical lymphadenopathyUnderwent mastectomyChemotherapy regimenChemotherapy regimensLocal progressionStage diseaseFurther therapyClinicopathologic dataDistant metastasisMedical oncologistsPredictors of tumor progression during neoadjuvant chemotherapy in breast cancer
Caudle A, Gonzalez-Angulo A, Kelly H, Liu P, Pusztai L, Symmans W, Kuerer H, Mittendorf E, Hortobagyi G, Meric-Bernstam F. Predictors of tumor progression during neoadjuvant chemotherapy in breast cancer. Journal Of Clinical Oncology 2009, 27: 603-603. DOI: 10.1200/jco.2009.27.15_suppl.603.Peer-Reviewed Original ResearchNeoadjuvant chemotherapyHigh Ki-67High tumor gradeStable diseasePR statusBreast cancerTumor gradeKi-67Negative ERNegative ER/PR statusFirst-line surgical approachSingle comprehensive cancer centerTumor progressionER/PR statusTaxane-based regimensComplete pathologic responseSubset of patientsLymph node metastasisHigher T stageComprehensive cancer centerPre-treatment characteristicsNCT regimenLymphovascular invasionMost patientsPathologic response
2006
Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits
Yang CH, Gonzalez-Angulo AM, Reuben JM, Booser DJ, Pusztai L, Krishnamurthy S, Esseltine D, Stec J, Broglio KR, Islam R, Hortobagyi GN, Cristofanilli M. Bortezomib (VELCADE®) in metastatic breast cancer: pharmacodynamics, biological effects, and prediction of clinical benefits. Annals Of Oncology 2006, 17: 813-817. PMID: 16403809, DOI: 10.1093/annonc/mdj131.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBone NeoplasmsBoronic AcidsBortezomibBreast NeoplasmsDisease ProgressionDisease-Free SurvivalFemaleHumansMaleMaximum Tolerated DoseMiddle AgedPleural NeoplasmsProtease InhibitorsPyrazinesReceptors, EstrogenReceptors, ProgesteroneSoft Tissue NeoplasmsSurvival RateTreatment OutcomeConceptsMetastatic breast cancerBreast cancerPlasma interleukin-6 levelsCommon grade 3Limited clinical activityClinical response ratePhase II studyInterleukin-6 levelsMedian survival timeWeek of restBroad antitumor activityStable diseaseII studyObjective responseSkin rashClinical effectsClinical benefitDisease progressionClinical activityGrade 3Pharmacodynamic dataSurvival timeMean inhibitionSingle agentResponse rate
2005
Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma
Pusztai L, Wagner P, Ibrahim N, Rivera E, Theriault R, Booser D, Symmans FW, Wong F, Blumenschein G, Fleming DR, Rouzier R, Boniface G, Hortobagyi GN. Phase II study of tariquidar, a selective P‐glycoprotein inhibitor, in patients with chemotherapy‐resistant, advanced breast carcinoma. Cancer 2005, 104: 682-691. PMID: 15986399, DOI: 10.1002/cncr.21227.Peer-Reviewed Original ResearchConceptsAdministration of tariquidarP-gp expressionSestamibi scanBreast carcinomaSestamibi uptakeP-gp-positive tumorsTaxane-containing chemotherapy regimensDocetaxel-related toxicitiesLimited clinical activityObjective tumor responsePercent of patientsPhase II studyAdvanced breast carcinomaP-glycoprotein inhibitor tariquidarP-glycoprotein inhibitorsMultidrug resistance modulationP-gp transporterMultidrug resistance inhibitorsSame chemotherapyStable diseaseChemotherapy regimenChemotherapy regimensTaxane chemotherapyClinical responseDose modification
2003
Phase I and II study of exisulind in combination with capecitabine in patients with metastatic breast cancer.
Pusztai L, Zhen JH, Arun B, Rivera E, Whitehead C, Thompson WJ, Nealy KM, Gibbs A, Symmans WF, Esteva FJ, Booser D, Murray JL, Valero V, Smith TL, Hortobagyi GN. Phase I and II study of exisulind in combination with capecitabine in patients with metastatic breast cancer. Journal Of Clinical Oncology 2003, 21: 3454-61. PMID: 12972520, DOI: 10.1200/jco.2003.02.114.Peer-Reviewed Original ResearchMeSH Keywords3',5'-Cyclic-GMP PhosphodiesterasesAdultAgedAntimetabolites, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCapecitabineCyclic Nucleotide Phosphodiesterases, Type 2Cyclic Nucleotide Phosphodiesterases, Type 5DeoxycytidineFemaleFluorouracilHumansImmunohistochemistryMiddle AgedNeoplasm MetastasisPhosphoric Diester HydrolasesProdrugsSulindacConceptsMetastatic breast cancerHand-foot syndromeAdverse eventsBreast cancerGrade 2Strong stainingPhase IContinuous daily therapyFrequent grade 2Dose-limiting toxicityOverall clinical benefitPercent of tumorsUnexpected adverse eventsPhase II testingBID dosePrevious anthracyclineStable diseaseDaily therapyTaxane chemotherapyLaboratory abnormalitiesMedian durationPartial responseClinical benefitTumor responseImmunohistochemical assessment
2001
Chemotherapy-induced histologic changes in mastectomy specimens and their potential significance
Sneige N, Kemp B, Pusztai L, Asmar L, Hortobagyi G. Chemotherapy-induced histologic changes in mastectomy specimens and their potential significance. The Breast 2001, 10: 492-500. PMID: 14965629, DOI: 10.1054/brst.2001.0310.Peer-Reviewed Original ResearchTumor responseHistologic changesCytologic changesComplete responseOverall survivalLymph nodesBreast cancerBreast tissueNon-neoplastic breast tissueHistologic complete responseNeoplastic breast epitheliumPost-chemotherapy tumorsPostmenopausal breast tissueClinical tumor responseRelapse-free survivalPercent of tumorsPathologic tumor responseStable diseasePreoperative chemotherapyPreoperative treatmentPartial responsePathologic assessmentHistologic confirmationPerilobular fibrosisResidual tumor
1999
Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony-stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy
Pusztai L, Holmes F, Fraschini G, Hortobagyi G. Phase II study of mitoxantrone by 14-day continuous infusion with granulocyte colony-stimulating factor (GCSF) support in patients with metastatic breast cancer and limited prior therapy. Cancer Chemotherapy And Pharmacology 1999, 43: 86-91. PMID: 9923546, DOI: 10.1007/s002800050867.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerGranulocyte colony-stimulating factor supportColony-stimulating factor supportObjective response ratePhase II studyContinuous infusionBreast cancerII studyFactor supportSide effectsResponse rateMajor dose-limiting side effectDose-limiting side effectDiscontinuation of therapySecond-line chemotherapySecond-line regimensPhase II evaluationComplete tumor responseContinuous intravenous infusionMaximal cytotoxic effectLimited antitumor activityAsymptomatic cardiotoxicityPrevious therapyStable diseaseMetastatic disease
1998
Daily Oral Etoposide in Patients With Heavily Pretreated Metastatic Breast Cancer
Pusztai L, Walters R, Valero V, Theriault R, Hortobagyi G. Daily Oral Etoposide in Patients With Heavily Pretreated Metastatic Breast Cancer. American Journal Of Clinical Oncology 1998, 21: 442-446. PMID: 9781596, DOI: 10.1097/00000421-199810000-00004.Peer-Reviewed Original ResearchConceptsGrade 4 toxicityMetastatic breast cancerSignificant hematologic toxicityOral etoposideBreast cancerGrade 2Hematologic toxicityDaily oral etoposideFourth-line agentZubrod performance statusPercent of patientsPhase II studyMajority of patientsGreater thrombocytopeniaNeutropenic feverStable diseasePrevious therapyRadiologic evidenceII studyMedian durationPartial responsePerformance statusMedian ageMore regimensSevere anemiaHigh-dose chemotherapy: how resistant is breast cancer?
Pusztai L, Hortobagyi G. High-dose chemotherapy: how resistant is breast cancer? Drug Resistance Updates 1998, 1: 62-72. PMID: 17092798, DOI: 10.1016/s1368-7646(98)80216-1.Peer-Reviewed Original ResearchHigh-dose chemotherapyClinical drug resistanceBreast cancerDrug resistancePartial responseClinical patternResponse rateComplete response rateHigh-dose therapyInitial complete responseObjective response rateStandard-dose chemotherapyDifferent clinical patternsMajority of patientsPrimary drug resistanceStem cell supportHigh cure ratesDrug-resistant clonesInduction therapyInitial chemosensitivityPathologic resistanceStable diseaseCancer dieOverall survivalComplete response