2018
A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT)
Mateo J, Chakravarty D, Dienstmann R, Jezdic S, Gonzalez-Perez A, Lopez-Bigas N, Ng CKY, Bedard PL, Tortora G, Douillard J, Van Allen EM, Schultz N, Swanton C, André F, Pusztai L. A framework to rank genomic alterations as targets for cancer precision medicine: the ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). Annals Of Oncology 2018, 29: 1895-1902. PMID: 30137196, PMCID: PMC6158764, DOI: 10.1093/annonc/mdy263.Peer-Reviewed Original ResearchConceptsESMO ScaleMolecular targetsClinical actionabilityPrecision Medicine Working GroupGenomic alterationsPrecision medicineRoutine clinical decisionEvidence-based criteriaMedicine Working GroupLack of evidencePreclinical evidenceClinical benefitClinical evidencePatient populationClassification systemClinical managementCancer precision medicineInvestigational targetsPatient managementMolecular aberrationsTumor typesClinical decisionClinical targetsAvailable evidenceEuropean Society
2015
Immunotherapy opportunities in breast cancer.
Pusztai L, Ladányi A, Székely B, Dank M. Immunotherapy opportunities in breast cancer. Magyar Onkológia 2015, 60: 34-40. PMID: 26934349.Peer-Reviewed Original ResearchConceptsAnti-tumor immune responseLocal anti-tumour immune responseBreast cancerImmune responseClinical trialsEffective immune checkpoint inhibitorsEarly-stage breast cancerTriple-negative breast cancerPhase I clinical trialImmune checkpoint inhibitorsTumor response rateExtensive lymphocytic infiltrationPD-L1 antibodiesDirect clinical evidenceBreast cancer patientsStage breast cancerNew treatment modalitiesNegative breast cancerCheckpoint inhibitorsChemotherapy regimensMetastatic settingNeoadjuvant chemotherapyLymphocytic infiltrationClinical benefitClinical evidenceHigh HER2 Expression Correlates with Response to the Combination of Lapatinib and Trastuzumab
Scaltriti M, Nuciforo P, Bradbury I, Sperinde J, Agbor-Tarh D, Campbell C, Chenna A, Winslow J, Serra V, Parra JL, Prudkin L, Jimenez J, Aura C, Harbeck N, Pusztai L, Ellis C, Eidtmann H, Arribas J, Cortes J, de Azambuja E, Piccart M, Baselga J. High HER2 Expression Correlates with Response to the Combination of Lapatinib and Trastuzumab. Clinical Cancer Research 2015, 21: 569-576. PMID: 25467182, DOI: 10.1158/1078-0432.ccr-14-1824.Peer-Reviewed Original ResearchConceptsProgression-free survivalPathologic complete responseAnti-HER2 therapyHER2 expressionBreast cancerLonger progression-free survivalCombination of lapatinibExpression of p95HER2Trastuzumab-based therapyHigh HER2 expressionMetastatic breast cancerHER2 protein expressionComplete responseHR statusClinical benefitPrimary tumorHER2 levelsCox modelP95HER2PatientsPositive subsetTrastuzumabLapatinibHER2Expression correlates
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
Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas
Delpech Y, Coutant C, Hsu L, Barranger E, Iwamoto T, Barcenas CH, Hortobagyi GN, Rouzier R, Esteva FJ, Pusztai L. Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas. British Journal Of Cancer 2013, 108: 285-291. PMID: 23299541, PMCID: PMC3566807, DOI: 10.1038/bjc.2012.557.Peer-Reviewed Original ResearchConceptsInvasive ductal carcinomaBreast-conserving surgeryNeoadjuvant chemotherapyPure lobular carcinomaLobular carcinomaClinical benefitTumor sizeER-positive invasive ductal carcinomasLower pathological complete response rateResponse ratePathological complete response ratePathological response rateComplete response rateGood clinical responsePathological complete responseType of chemotherapyPositive surgical marginsSurgical resection marginsClinical responseNodal statusComplete responseResection marginsSurgical marginsDuctal carcinomaPositive margins
2012
Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer
Delpech Y, Wu Y, Hess KR, Hsu L, Ayers M, Natowicz R, Coutant C, Rouzier R, Barranger E, Hortobagyi GN, Mauro D, Pusztai L. Ki67 expression in the primary tumor predicts for clinical benefit and time to progression on first-line endocrine therapy in estrogen receptor-positive metastatic breast cancer. Breast Cancer Research And Treatment 2012, 135: 619-627. PMID: 22890751, DOI: 10.1007/s10549-012-2194-2.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalBreast NeoplasmsBreast Neoplasms, MaleCarcinoma, Ductal, BreastDisease-Free SurvivalFemaleHumansKaplan-Meier EstimateKi-67 AntigenMaleMiddle AgedMultivariate AnalysisNeoplasm Recurrence, LocalNeoplasms, Hormone-DependentProportional Hazards ModelsReceptors, EstrogenRetrospective StudiesTreatment OutcomeConceptsFirst-line endocrine therapyEndocrine therapyMetastatic breast cancerMetastatic diseaseKi67 expressionClinical benefitPrimary tumorBreast cancerExpression groupEstrogen receptor-positive metastatic breast cancerIndependent adverse prognostic factorKaplan-Meier survival curvesClinical benefit rateKi67 expression levelsAdverse prognostic factorMedian survival timeLow Ki67 expressionBreast cancer correlatesHigh Ki67 expressionHigh clinical benefitPrognostic factorsMedian timeMetastatic recurrencePrimary cancerImmunohistochemical variables
2007
Markers predicting clinical benefit in breast cancer from microtubule-targeting agents
Pusztai L. Markers predicting clinical benefit in breast cancer from microtubule-targeting agents. Annals Of Oncology 2007, 18: xii15-xii20. PMID: 18083698, DOI: 10.1093/annonc/mdm534.Peer-Reviewed Original ResearchConceptsMicrotubule-targeting agentsSubset of patientsEstrogen receptor negativityBreast cancer patientsNon-cross resistanceMicrotubule-associated protein tauMechanism of actionReceptor negativityClinical benefitPatient groupCancer patientsClinical trialsPoor responseHER2 amplificationClinical dataClinical studiesBreast cancerTaxane resistanceBetaIII-tubulinProtein tauP-glycoproteinPharmacogenomic analysisTaxanesLow expressionPatients
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
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