2024
Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.
Chavez-MacGregor M, Miao J, Pusztai L, Goetz M, Rastogi P, Ganz P, Mamounas E, Paik S, Bandos H, Razaq W, O'Dea A, Kaklamani V, Silber A, Flaum L, Andreopoulou E, Wendt A, Carney J, Sharma P, Gralow J, Lew D, Barlow W, Hortobagyi G. Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer. Journal Of Clinical Oncology 2024, jco2302344. PMID: 38833643, DOI: 10.1200/jco.23.02344.Peer-Reviewed Original ResearchInvasive disease-free survivalHormone receptor-positiveEndocrine therapyOverall survivalBreast cancerHazard ratioReceptor-positiveHigh riskSubset analysisHormone receptor-positive metastatic breast cancerRisk groupsHormone receptor-positive BCEarly-stage breast cancerStratified log-rank testProgression-free survivalEfficacy of everolimusDisease-free survivalMetastatic breast cancerPlacebo-controlled trialSecondary end pointsLog-rank testHighest grade 3Treatment completion ratesPhase IIIEverolimus arm
2023
Comparing the prognostic and predictive utility of serum thymidine kinase 1 and CA 15-3 in patients with hormone receptor positive metastatic breast cancer starting first-line endocrine therapy in SWOG S0226.
Cobain E, Barlow W, Paoletti C, Bergqvist M, Williams A, Ritzen H, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Comparing the prognostic and predictive utility of serum thymidine kinase 1 and CA 15-3 in patients with hormone receptor positive metastatic breast cancer starting first-line endocrine therapy in SWOG S0226. Journal Of Clinical Oncology 2023, 41: 1076-1076. DOI: 10.1200/jco.2023.41.16_suppl.1076.Peer-Reviewed Original ResearchProgression-free survivalMetastatic breast cancerThymidine kinase 1 activityHormone receptor-positive metastatic breast cancerPositive metastatic breast cancerOverall survivalEndocrine therapyCA 15Breast cancerCA15-3Predictors of PFSFirst-line endocrine therapySubsequent progression-free survivalWorse progression-free survivalSerum thymidine kinase 1Systemic endocrine therapyMultivariable Cox modelCox regression analysisWorse overall survivalHypothesis-generating dataCycles of treatmentTamoxifen useSystemic therapySerum levelsMultivariable analysisThymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)
Bergqvist M, Nordmark A, Williams A, Paoletti C, Barlow W, Cobain E, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). Biomarkers 2023, 28: 313-322. PMID: 36647745, PMCID: PMC10681159, DOI: 10.1080/1354750x.2023.2168063.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerNegative predictive valueEndocrine therapyThymidine kinase activityLower riskSingle-agent endocrine therapyMetastatic breast cancer patientsLonger progression-free survivalHigh negative predictive valueProgression-free survivalBreast cancer patientsSerum thymidine kinase activityAdditional therapyOverall survivalSuch patientsCancer patientsBlood drawEarly progressionDisease progressionRapid progressionBreast cancerPatientsSubsequent timepointsPredictive valuePotential biomarkersCisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial
Rodler E, Sharma P, Barlow W, Gralow J, Puhalla S, Anders C, Goldstein L, Tripathy D, Brown-Glaberman U, Huynh T, Szyarto C, Godwin A, Pathak H, Swisher E, Radke M, Timms K, Lew D, Miao J, Pusztai L, Hayes D, Hortobagyi G. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2023, 24: 162-174. PMID: 36623515, PMCID: PMC9924094, DOI: 10.1016/s1470-2045(22)00739-2.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerMedian progression-free survivalProgression-free survivalMetastatic breast cancerMetastatic triple-negative breast cancerGermline BRCA1/2Phase 2 trialVeliparib groupPlacebo groupPlatinum-based chemotherapyBreast cancerHomologous recombination deficiencyAdverse eventsPARP inhibitorsEligible patientsMetastatic diseaseEastern Cooperative Oncology Group performance statusBRCA mutation-associated breast cancerInvestigator-assessed progression-free survivalTreatment-related adverse eventsRecurrent triple-negative breast cancerAcademic clinical sitesAddition of veliparibCommon grade 3Lines of chemotherapy
2021
A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222
Moore HCF, Barlow WE, Somlo G, Gralow JR, Schott AF, Hayes DF, Kuhn P, Hicks JB, Welter L, Dy PA, Yeon CH, Conlin AK, Balcueva E, Lew DL, Tripathy D, Pusztai L, Hortobagyi GN. A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222. Clinical Cancer Research 2021, 28: 611-617. PMID: 34844978, PMCID: PMC9782801, DOI: 10.1158/1078-0432.ccr-21-3131.Peer-Reviewed Original ResearchConceptsProgression-free survivalHER2-negative breast cancerFirst-line treatmentBreast cancerAdvanced hormone receptor-positive breast cancerAdvanced hormone-sensitive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerHormone-sensitive breast cancerRandomized placebo-controlled trialReceptor-positive breast cancerCombination endocrine therapyMetastatic hormone receptorPlacebo-controlled trialAdvanced breast cancerMainstay of treatmentFront-line treatmentBaseline CTCsEndocrine therapyEndocrine treatmentPostmenopausal womenMetastatic diseaseOverall survivalPrognostic impactSystemic therapyEvaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial
Paoletti C, Barlow WE, Cobain EF, Bergqvist M, Mehta RS, Gralow JR, Hortobagyi GN, Albain KS, Pusztai L, Sharma P, Godwin AK, Thompson AM, Hayes DF, Rae JM. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial. Clinical Cancer Research 2021, 27: clincanres.1562.2021. PMID: 34521624, PMCID: PMC8595696, DOI: 10.1158/1078-0432.ccr-21-1562.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicFemaleHumansKaplan-Meier EstimateMiddle AgedPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesThymidine KinaseTreatment OutcomeConceptsProgression-free survivalMetastatic breast cancerFirst-line endocrine therapyOverall survivalEndocrine therapyHormone receptor-positive metastatic breast cancer patientsHormone receptor-positive metastatic breast cancerPositive metastatic breast cancer patientsSubsequent progression-free survivalMetastatic breast cancer patientsWorse progression-free survivalCombination endocrine therapySerum thymidine kinase 1Trial of anastrozoleThymidine kinase 1 activityBreast cancer patientsLog-rank testLine endocrine therapyDu/LAdjuvant tamoxifenPrognostic effectCox regressionPoor prognosisWorse prognosisKaplan-Meier
2020
SGNLVA-001: A phase I open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer.
Beckwith H, Medgyesy D, Abraham J, Nanda R, Tkaczuk K, Krop I, Pusztai L, Modi S, Mita M, Specht J, Hurvitz S, Han H, Kalinsky K, Wilks S, O'Shaughnessy J, Hart L, Rugo H, Mitri Z, Garfin P, Burris III H. SGNLVA-001: A phase I open-label dose escalation and expansion study of SGN-LIV1A administered weekly in breast cancer. Journal Of Clinical Oncology 2020, 38: tps1104-tps1104. DOI: 10.1200/jco.2020.38.15_suppl.tps1104.Peer-Reviewed Original ResearchMetastatic breast cancerMonomethyl auristatin EDose-expansion cohortsAntibody-drug conjugatesDose escalationBreast cancerRECIST v1.1Expansion cohortPrior linesCytotoxic chemotherapyMetastatic triple-negative breast cancerGrade 2 peripheral neuropathyInvestigational antibody-drug conjugateNegative metastatic breast cancerLIV-1Triple-negative breast cancerAdequate organ functionHumanized IgG1 monoclonal antibodyKey efficacy endpointsPrimary safety endpointProgression-free survivalDose-limiting toxicityDuration of responseOverall response rateMonths of completionOverall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis
Schettini F, Giudici F, Giuliano M, Cristofanilli M, Arpino G, Del Mastro L, Puglisi F, De Placido S, Paris I, De Placido P, Venturini S, De Laurentis M, Conte P, Juric D, Llombart-Cussac A, Pusztai L, Prat A, Jerusalem G, Di Leo A, Generali D. Overall Survival of CDK4/6-Inhibitor–Based Treatments in Clinically Relevant Subgroups of Metastatic Breast Cancer: Systematic Review and Meta-Analysis. Journal Of The National Cancer Institute 2020, 112: 1089-1097. PMID: 32407488, PMCID: PMC7669227, DOI: 10.1093/jnci/djaa071.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials, Phase II as TopicClinical Trials, Phase III as TopicCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6FemaleHumansLetrozoleNeoplasm MetastasisPiperazinesProtein Kinase InhibitorsPyridinesRandomized Controlled Trials as TopicConceptsSecond-line therapyMetastatic breast cancerEndocrine therapyCDK4/6 inhibitorsVisceral involvementBreast cancerPostmenopausal metastatic breast cancerAvailable phase IIChemotherapy-naïve patientsClear OS benefitSpecific clinical subgroupsProgression-free survivalOverall survival dataBreast cancer prognosisStudy-level factorsCyclin-dependent kinase 4Random-effects modelSystematic literature searchEndocrine monotherapyOS benefitOS independentOverall survivalUpfront therapyMenopausal statusMetastatic sites
2018
Long‐Term Survival of De Novo Stage IV Human Epidermal Growth Receptor 2 (HER2) Positive Breast Cancers Treated with HER2‐Targeted Therapy
Wong Y, Raghavendra AS, Hatzis C, Irizarry JP, Vega T, Horowitz N, Barcenas CH, Chavez‐MacGregor M, Valero V, Tripathy D, Pusztai L, Murthy RK. Long‐Term Survival of De Novo Stage IV Human Epidermal Growth Receptor 2 (HER2) Positive Breast Cancers Treated with HER2‐Targeted Therapy. The Oncologist 2018, 24: 313-318. PMID: 30139836, PMCID: PMC6519755, DOI: 10.1634/theoncologist.2018-0213.Peer-Reviewed Original ResearchConceptsDe novo stage IVProgression-free survivalMetastatic breast cancerHigher progression-free survivalPositive metastatic breast cancerExcellent long-term outcomesOverall survivalLong-term outcomesNED statusBreast cancerStage IVOS ratesLocoregional therapyRandomized studyDe novo stage IV diseaseDisease statusHER2-Targeted TherapyMedian overall survivalStage IV diseaseFirst-line therapyTrastuzumab-based therapyEstrogen receptor-positive statusPositive breast cancerImportant therapeutic goalNED patients
2017
Long-term survival of de novo stage IV human epidermal growth factor receptor 2 (HER2)-positive breast cancers treated with HER2 targeted therapy.
Wong Y, Raghavendra A, Hatzis C, Irizarry J, Vega T, Barcenas C, Chavez-Mac Gregor M, Valero V, Tripathy D, Pusztai L, Murthy R. Long-term survival of de novo stage IV human epidermal growth factor receptor 2 (HER2)-positive breast cancers treated with HER2 targeted therapy. Journal Of Clinical Oncology 2017, 35: 1021-1021. DOI: 10.1200/jco.2017.35.15_suppl.1021.Peer-Reviewed Original ResearchProgression-free survivalLonger progression-free survivalPositive breast cancerHER2-positive cancersMedian OSNED patientsOS ratesFree survivalOverall survivalPositive cancersBreast cancerDe novo stage IV diseaseHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2MD Anderson Cancer CenterStage IV diseaseAggressive multimodality therapyEvidence of diseaseFirst-line therapyGrowth factor receptor 2Year of diagnosisEarly-stage patientsAnderson Cancer CenterLong-term survival
2015
A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer
Generali D, Venturini S, Rognoni C, Ciani O, Pusztai L, Loi S, Jerusalem G, Bottini A, Tarricone R. A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer. Breast Cancer Research And Treatment 2015, 152: 95-117. PMID: 26044370, DOI: 10.1007/s10549-015-3453-9.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerHazard ratioMegestrol acetateResponse rateBreast cancerEstrogen receptor-positive metastatic breast cancerPFS/TTPSecond-line therapySecond-line treatmentToxicity of chemotherapyOverall response rateBetter response rateCapecitabineStandard pairwiseTamoxifenSunitinibChemotherapyTTP differenceMultiple treatmentsNMAIndividual studiesEverolimusExemestaneCancerHigh 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
2012
Progression of genomic signatures in local and metastatic estrogen receptor-positive (ER+) breast cancer: Relevance to palliative treatment.
Symmans W, Andreopoulou E, Booser D, Hatzis C, Wallace M, Zhang Y, Gong Y, Ignatiadis M, Sotiriou C, Andre F, Peintinger F, Regitnig P, Marth C, Desmedt C, Loi S, Moulder S, Hortobagyi G, Pusztai L, Valero V. Progression of genomic signatures in local and metastatic estrogen receptor-positive (ER+) breast cancer: Relevance to palliative treatment. Journal Of Clinical Oncology 2012, 30: 515-515. DOI: 10.1200/jco.2012.30.15_suppl.515.Peer-Reviewed Original ResearchProgression-free survivalOverall survivalBreast cancerHormonal therapyStage IIBStage IIIMetastatic estrogen receptor-positive breast cancerStage IVGenomic subtypesEstrogen receptor-positive breast cancerStage progressionReceptor-positive breast cancerPalliative hormonal therapyAJCC stage ICox regression analysisHigh-risk subtypesClinical progressionStage IIARisk subtypesBiopsy samplesStage IStaging methodMBC samplesTreatment typeCancer
2011
First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations
Iwamoto T, Lee JS, Bianchini G, Hubbard RE, Young E, Matsuoka J, Kim SB, Symmans WF, Hortobagyi GN, Pusztai L. First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlapping patient populations. Breast Cancer Research And Treatment 2011, 130: 155. PMID: 21833625, DOI: 10.1007/s10549-011-1706-9.Peer-Reviewed Original ResearchConceptsLong-term survivalPrognostic gene signatureClinical variablesChemotherapy responseGenomic prognostic markersPrognostic markerPredictive valueKaplan-Meir survival curvesSignificant independent predictive valuePathologic complete responseProgression-free survivalLong-term followIndependent predictive valueSame patient cohortReceiver operator characteristic curveOperator characteristic curveOverall survivalPreoperative chemotherapyComplete responseNodal statusIndependent prognosticClinicopathological variablesPatient populationHER2 statusPatient cohort
2010
Do experts agree on how to assess disease progression (DP) and progression-free survival (PFS) in phase III trials? A survey with experts in breast cancer research.
Saad E, Katz A, Pusztai L, Hoff P, Buyse M. Do experts agree on how to assess disease progression (DP) and progression-free survival (PFS) in phase III trials? A survey with experts in breast cancer research. Journal Of Clinical Oncology 2010, 28: 1084-1084. DOI: 10.1200/jco.2010.28.15_suppl.1084.Peer-Reviewed Original ResearchProgression-free survivalDisease progressionPhase III trialsBreast cancer researchIII trialsCancer researchProgressionTrials
2009
Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials
Mazouni C, André F, Broglio K, Pusztai L, Hortobagyi G. Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials. Journal Of Clinical Oncology 2009, 27: 1046-1046. DOI: 10.1200/jco.2009.27.15_suppl.1046.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalER-negative diseaseEfficacy of docetaxelBreast cancerER expressionResponse rateRandomized trialsDisease progressionEstrogen receptor-positive metastatic breast cancerPositive metastatic breast cancerCox proportional hazards modelTumor response rateER-positive patientsER-negative cancersEstrogen receptor expressionProportional hazards modelEffect of docetaxelHazard ratioDocetaxel efficacyPooled analysisTumor responseReceptor expressionHazards modelPatients
2004
Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma
Esteva FJ, Sahin AA, Smith TL, Yang Y, Pusztai L, Nahta R, Buchholz TA, Buzdar AU, Hortobagyi GN, Bacus SS. Prognostic significance of phosphorylated P38 mitogen‐activated protein kinase and HER‐2 expression in lymph node‐positive breast carcinoma. Cancer 2004, 100: 499-506. PMID: 14745865, DOI: 10.1002/cncr.11940.Peer-Reviewed Original ResearchMeSH KeywordsAgedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBiopsy, NeedleBreast NeoplasmsCombined Modality TherapyFemaleGene Expression Regulation, NeoplasticHumansImmunohistochemistryLymph NodesMastectomyMiddle AgedMitogen-Activated Protein KinasesNeoplasm StagingP38 Mitogen-Activated Protein KinasesProbabilityPrognosisProportional Hazards ModelsReceptor, ErbB-2Risk AssessmentSensitivity and SpecificitySurvival AnalysisTreatment OutcomeConceptsLymph node positive breast carcinomaNode-positive breast carcinomaProgression-free survivalP-p38 MAPKShorter progression-free survivalHER-2 expressionP-p38 MAPK expressionBreast carcinomaAdjuvant chemotherapyMAPK expressionKi-67Phosphorylated p38 MAPK expressionInitial cancer surgeryPrimary breast carcinomaInvasive breast carcinomaP38 MAPK expressionP38 mitogen-activated protein kinase phosphorylationPhosphorylated p38 mitogen-activated protein kinaseMitogen-activated protein kinase phosphorylationBreast carcinoma cellsAdjuvant fluorouracilMedian followCyclophosphamide chemotherapyCancer surgeryPoor outcome