2023
Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest
Kim L, Coman M, Pusztai L, Park T. Neoadjuvant Immunotherapy in Early, Triple-Negative Breast Cancers: Catching Up with the Rest. Annals Of Surgical Oncology 2023, 30: 6441-6449. PMID: 37349612, DOI: 10.1245/s10434-023-13714-x.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerTumor mutational burdenBreast cancerAdjuvant therapyPathological complete response rateImmune checkpoint modulationComplete response rateExcellent clinical outcomesCombination immunochemotherapyNeoadjuvant immunotherapyNeoadjuvant settingNeoadjuvant chemotherapyOverall survivalPD-L1Checkpoint modulationClinical outcomesMajor trialsMutational burdenResponse rateCancer typesCancerTherapyBiomarkersOutcomesExciting advancesHRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC).
Jeon J, Chen K, Madison R, Schrock A, Sokol E, Levy M, Oxnard G, Huang R, Pusztai L. HRD signature and HRD genomic landscape of tumors from 896 patients with early-stage breast cancer (BC). Journal Of Clinical Oncology 2023, 41: 539-539. DOI: 10.1200/jco.2023.41.16_suppl.539.Peer-Reviewed Original ResearchEarly-stage breast cancerPrimary breast cancerEarly breast cancerBreast cancerStage IHR-/HER2HRR deficiencyPALB2 mutationsEarly-stage primary breast cancerPARP inhibitorsStage IV diseaseHormone receptor statusMonths of diagnosisPositive breast cancerHomologous recombination repairComprehensive genomic profilingHRD signaturesClinical trial dataHigh rateSEER studySomatic BRCAAdjuvant therapyAdvanced diseaseReceptor statusBC subtypes
2022
Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021
Chehayeb R, Hood A, Wang X, Miksad R, Mougalian S, Lustberg M, Wang S, Greenup R, Pusztai L, Kunst N. Treatment Sequencing Patterns and Associated Direct Medical Costs of Metastatic Breast Cancer Care in the United States, 2011 to 2021. JAMA Network Open 2022, 5: e2244204. PMID: 36445704, PMCID: PMC9709649, DOI: 10.1001/jamanetworkopen.2022.44204.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerErbB2-positive metastatic breast cancerHR-positive metastatic breast cancerLines of therapyMBC subtypesDrug costsBreast cancerMedical costsHuman epidermal growth factor receptor 2 receptor statusMBC treatmentERBB2-negative metastatic breast cancerAssociated direct medical costsEarly-stage breast cancerHormone receptorsFlatiron Health databaseMetastatic recurrence ratesDifferent drug regimensBreast cancer careData of patientsDirect medical costsNovel adjuvant therapySupportive care drugsOutcomes of interestCost-effectiveness analysisAdjuvant therapyEvent-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer
Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O'Shaughnessy J. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal Of Medicine 2022, 386: 556-567. PMID: 35139274, DOI: 10.1056/nejmoa2112651.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantFemaleHumansIntention to Treat AnalysisKaplan-Meier EstimateMiddle AgedNeoadjuvant TherapyProgression-Free SurvivalTriple Negative Breast NeoplasmsConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalCycles of pembrolizumabPathological complete responseDefinitive surgeryBreast cancerNeoadjuvant chemotherapyComplete responseLonger event-free survivalUntreated stage IIPrimary end pointPhase 3 trialSecond primary cancerDoxorubicin-cyclophosphamideNeoadjuvant pembrolizumabNeoadjuvant phaseAdjuvant therapyDistant recurrenceNeoadjuvant therapyAdverse eventsPrimary cancerSafety profileDisease progressionPembrolizumab
2021
Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy
Foldi J, Rozenblit M, Park TS, Knowlton CA, Golshan M, Moran M, Pusztai L. Optimal Management for Residual Disease Following Neoadjuvant Systemic Therapy. Current Treatment Options In Oncology 2021, 22: 79. PMID: 34213636, DOI: 10.1007/s11864-021-00879-4.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual cancerClinical trialsAdjuvant therapyExcellent long-term disease-free survivalLong-term disease-free survivalAxillary lymph node dissectionHuman epidermal growth factor receptor 2Early-stage breast cancerEpidermal growth factor receptor 2Post-mastectomy breastSystemic adjuvant therapyInternal mammary nodesLymph node dissectionNeoadjuvant systemic therapyDisease-free survivalGrowth factor receptor 2Minimal residual disease monitoringRecurrence-free survivalType of surgeryPivotal clinical trialsOngoing clinical trialsFactor receptor 2Residual disease monitoringAccurate prognostic estimates
2018
KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant therapy followed by pembro vs placebo as adjuvant therapy for triple-negative breast cancer (TNBC).
Schmid P, Cortes J, Bergh J, Pusztai L, Denkert C, Verma S, McArthur H, Kummel S, Ding Y, Karantza V, Dang T, Dent R. KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant therapy followed by pembro vs placebo as adjuvant therapy for triple-negative breast cancer (TNBC). Journal Of Clinical Oncology 2018, 36: tps602-tps602. DOI: 10.1200/jco.2018.36.15_suppl.tps602.Peer-Reviewed Original ResearchComparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies
Wei W, Kurita T, Hess KR, Sanft T, Szekely B, Hatzis C, Pusztai L. Comparison of Residual Risk–Based Eligibility vs Tumor Size and Nodal Status for Power Estimates in Adjuvant Trials of Breast Cancer Therapies. JAMA Oncology 2018, 4: e175092-e175092. PMID: 29372234, PMCID: PMC5885272, DOI: 10.1001/jamaoncol.2017.5092.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantEligibility DeterminationFemaleHumansLymph NodesLymphatic MetastasisMiddle AgedNeoplasm Recurrence, LocalNeoplasm, ResidualPatient SelectionPrognosisRandomized Controlled Trials as TopicReproducibility of ResultsResearch DesignRetrospective StudiesRisk FactorsSurvival AnalysisTrastuzumabTumor BurdenWatchful WaitingYoung AdultConceptsTumor sizeAdjuvant trialsEligibility criteriaNodal statusClinical trialsResidual riskEarly-stage breast cancerAdjuvant clinical trialsBaseline prognostic riskFuture adjuvant trialsResidual risk estimatesRisk of recurrenceBreast cancer therapyRisk thresholdTrial powerClinical trial powerTrial eligibilityAdjuvant therapyCare therapyConsecutive patientsPrognostic riskPatient eligibilityTrial populationPatient cohortControl arm
2017
Discussion of: “Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?”
Chagpar AB, Horowitz N, Sanft T, Wilson LD, Silber A, Killelea B, Moran MS, DiGiovanna MP, Hofstatter E, Chung G, Pusztai L, Lannin DR. Discussion of: “Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?”. The American Journal Of Surgery 2017, 214: 1089-1090. PMID: 28987415, DOI: 10.1016/j.amjsurg.2017.09.025.Commentaries, Editorials and LettersDoes lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?
Chagpar AB, Horowitz N, Sanft T, Wilson LD, Silber A, Killelea B, Moran MS, DiGiovanna MP, Hofstatter E, Chung G, Pusztai L, Lannin DR. Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer? The American Journal Of Surgery 2017, 214: 1082-1088. PMID: 28939252, DOI: 10.1016/j.amjsurg.2017.07.036.Peer-Reviewed Original ResearchConceptsHormone receptor-positive breast cancerReceptor-positive breast cancerPositive breast cancerLymph nodesRadiation therapyBreast cancerPost-lumpectomy radiation therapyPost-mastectomy radiation therapyNational Cancer DatabaseSentinel LN biopsyBreast cancer patientsWomen 70 yearsAdjuvant chemotherapyAdjuvant therapyHormonal therapyLN biopsyLN evaluationLN statusCancer patientsCancer DatabasePatientsTherapyCancerChemotherapyHr233TiP KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant followed by pembro vs placebo as adjuvant therapy for triple-negative breast cancer (TNBC)
Schmid P, Castan J, Bergh J, Pusztai L, Denkert C, Verma S, McArthur H, Zhao J, Aktan G, Dang T, Dent R. 233TiP KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo + chemo as neoadjuvant followed by pembro vs placebo as adjuvant therapy for triple-negative breast cancer (TNBC). Annals Of Oncology 2017, 28: v72. DOI: 10.1093/annonc/mdx364.015.Peer-Reviewed Original ResearchNew Therapeutic Strategies for Triple-Negative Breast Cancer.
Székely B, Silber AL, Pusztai L. New Therapeutic Strategies for Triple-Negative Breast Cancer. Oncology 2017, 31: 130-7. PMID: 28205193.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerResidual cancerBreast cancerEarly-stage triple-negative breast cancerUnselected triple negative breast cancerIntroduction of taxanesOngoing adjuvant trialsImmune checkpoint inhibitorsSurvival of patientsImportant clinical trialsImportant therapeutic advanceBRCA-mutant cancersNew therapeutic strategiesAntibody-drug conjugatesAdjuvant trialsNeoadjuvant chemotherapyAdjuvant therapyCheckpoint inhibitorsIdentifies patientsTherapeutic advancesClinical trialsHigh riskTherapeutic strategiesCancerTrials
2013
A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories
Szekely B, Iwamoto T, Szasz AM, Qi Y, Matsuoka J, Symmans WF, Tokes AM, Kulka J, Swanton C, Pusztai L. A 3-gene proliferation score (TOP-FOX-67) can re-classify histological grade-2, ER-positive breast cancers into low- and high-risk prognostic categories. Breast Cancer Research And Treatment 2013, 138: 691-698. PMID: 23504136, DOI: 10.1007/s10549-013-2475-4.Peer-Reviewed Original ResearchMeSH KeywordsAntigens, NeoplasmBreast NeoplasmsCell ProliferationChemotherapy, AdjuvantCohort StudiesDatabases, GeneticDNA Topoisomerases, Type IIDNA-Binding ProteinsFemaleForkhead Box Protein M1Forkhead Transcription FactorsGene Expression Regulation, NeoplasticGenome, HumanHumansKi-67 AntigenPoly-ADP-Ribose Binding ProteinsPredictive Value of TestsPrognosisReceptors, EstrogenSurvival RateTamoxifenConceptsGenomic grade indexGrade 2 cancersPrognostic valueProliferation scoreBreast cancerDistant metastasis-free survival curvesGrade 2Metastasis-free survival curvesER-positive breast cancerSystemic adjuvant therapyHigh expressionCohort of patientsHistological grade 2Intermediate-risk cancerPositive breast cancerSimilar prognostic valueGrade 2 tumorsHigh-risk groupGrade 1 cancersHistological grade groupsNon-significant trendWorse DMFSAdjuvant tamoxifenAdjuvant therapyWorse survival
2012
19IN Does Molecular Triage Help to Identify Highly Sensitive Disease?
Pusztai L. 19IN Does Molecular Triage Help to Identify Highly Sensitive Disease? Annals Of Oncology 2012, 23: ix29. DOI: 10.1016/s0923-7534(20)32633-8.Peer-Reviewed Original ResearchResponse markersPredictive valueEstrogen receptor expressionHigher tumor proliferationTreatment response markersClass of drugsNegative predictive valuePositive predictive valueDriver eventsAdjuvant therapyPredictive biomarkersPredictive markerTreatment modalitiesTriage patientsVariety of agentsBaseline prognosisClinical trialsReceptor expressionBreast cancerSensitive diseaseHuman epidermal growth factorClinical utilityEpidermal growth factorChemotherapy sensitivityTumor proliferation172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups
Iwamoto T, Pusztai L, Matsuoka J, Callari M, Kelly C, Qi Y, Motoki T, Taira N, Santarpia L, Doihara H, Gianni L, Bianchini G. 172O ER + /HER2+ and ER-/Her2+ Breast Cancers are Molecularly Distinct but Immune Gene Signatures are Prognostic and Predictive in Both Groups. Annals Of Oncology 2012, 23: ix74-ix75. DOI: 10.1016/s0923-7534(20)32783-6.Peer-Reviewed Original ResearchPathologic complete responseER statusResidual diseaseER-/HER2HER2 cancersBetter prognosisBreast cancerHER2-positive breast cancerImmune gene signaturesSystemic adjuvant therapyPositive breast cancerEstrogen receptor statusHigher chemotherapy sensitivityDistinct molecular subtypesNeoadjuvant taxaneAdjuvant therapyImmune signaturesComplete responseReceptor statusHER2 patientsPoor prognosisMolecular subtypesChemotherapy sensitivityPredictive valueHER2Adjuvant Therapy in Stage I Carcinoma of the Breast: The Influence of Multigene Analyses and Molecular Phenotyping
Schwartz GF, Bartelink H, Burstein HJ, Cady B, Cataliotti L, Fentiman IS, Holland R, Hughes KS, Masood S, McCormick B, Palazzo JA, Pressman PI, Reis‐Filho J, Pusztai L, Rutgers EJ, Seidman AD, Solin LJ, Sparano JA. Adjuvant Therapy in Stage I Carcinoma of the Breast: The Influence of Multigene Analyses and Molecular Phenotyping. The Breast Journal 2012, 18: 303-311. PMID: 22759093, DOI: 10.1111/j.1524-4741.2012.01264.x.Peer-Reviewed Original ResearchConceptsStage I carcinomaAdjuvant therapyBreast cancerGene prognostic signaturePatient ageTumor sizeImmunohistochemical markersIndividual patientsConsensus conferencePrognostic signatureSteroid hormonesMolecular profilingNottingham indexMolecular phenotypingPatientsCarcinomaTherapyCancerBreastPrognosisPart of decisionHormoneUse of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC).
Pusztai L, Yelensky R, Wang B, Avritscher R, Symmans W, Lipson D, Palmer G, Moulder S, Stephens P, Wu Y, Cronin M. Use of next-generation sequencing (NGS) to detect high frequency of targetable alterations in primary and metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 10559-10559. DOI: 10.1200/jco.2012.30.15_suppl.10559.Peer-Reviewed Original ResearchMetastatic breast cancerClinical trialsNext-generation sequencingNeedle biopsyBreast cancerGenomic alterationsClinical treatment optionsHER2 gene amplificationPatient selection approachAdjuvant therapyTargetable alterationsTreatment optionsPIK3CA mutationsNovel agentsERBB2 alterationsInvestigational drugsTherapeutic implicationsCancer-related genesBiopsyPredictive valueProspective testingNGS profilingDriver mutationsTherapyCancerAdjuvant therapy in stage I carcinoma of the breast
Schwartz GF, Reis‐Fihlo J, Pusztai L, Fentiman IS, Holland R, Bartelink H, Rutgers EJ, Solin LJ, Palazzo J, Committee A. Adjuvant therapy in stage I carcinoma of the breast. Cancer 2012, 118: 2031-2038. PMID: 22392361, DOI: 10.1002/cncr.27431.Peer-Reviewed Original ResearchConceptsStage I breast cancerI breast cancerBreast cancerAdjuvant therapyConsensus conferenceStage ILymph node-negative breast cancerNode-negative breast cancerKimmel Cancer CenterAdjuvant chemotherapyAdjuvant hormonesAdjuvant treatmentCancer CenterClinical trialsThomas Jefferson UniversityTreatment criteriaTreatment decisionsIndividual tumorsCancerGenetic factorsChemotherapyMolecular phenotypingTherapyHormoneCurrent data
2011
Effect of CYP2D6 polymorphisms on breast cancer recurrence
Morrow PK, Serna R, Broglio K, Pusztai L, Nikoloff DM, Hillman GR, Fontecha M, Li R, Michaud L, Hortobagyi G, Gonzalez‐Angulo A. Effect of CYP2D6 polymorphisms on breast cancer recurrence. Cancer 2011, 118: 1221-1227. PMID: 21823108, DOI: 10.1002/cncr.26407.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCarcinomaCase-Control StudiesCohort StudiesCytochrome P-450 CYP2D6Cytochrome P-450 CYP2D6 InhibitorsEnzyme InhibitorsFemaleFollow-Up StudiesGenetic Predisposition to DiseaseHumansMastectomyMiddle AgedNeoplasm Recurrence, LocalPolymorphism, GeneticTamoxifenConceptsEarly breast cancerBreast cancer recurrenceAdjuvant tamoxifen therapyCancer recurrenceTamoxifen therapyMedical historyCYP2D6 genotypeTexas MD Anderson Cancer CenterFresh frozen tumor samplesCytochrome P450 2D6 polymorphismMD Anderson Cancer CenterBreast cancer patientsRisk of recurrenceCase-control studyAnderson Cancer CenterPatient's medical historyFrozen tumor samplesAdjuvant tamoxifenAdjuvant therapyConcomitant medicationsPatient characteristicsAmpliChip CYP450 TestCYP2D6 metabolismDisease recurrenceCancer CenterCoping with uncertainty: T1a,bN0M0 HER2-positive breast cancer, do we have a treatment threshold?
Kelly CM, Pritchard KI, Trudeau M, Andreopoulou E, Hess K, Pusztai L. Coping with uncertainty: T1a,bN0M0 HER2-positive breast cancer, do we have a treatment threshold? Annals Of Oncology 2011, 22: 2387-2393. PMID: 21406473, DOI: 10.1093/annonc/mdq786.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerBreast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Baseline risk estimatesBN0M0 breast cancerHER2-positive cohortNode-negative T1aStudy end pointDisease-free survivalRisks of therapyGrowth factor receptor 2Subset of patientsPositive breast cancerRetrospective database analysisHER2-negative cancersRecent retrospective studiesHER2-positive cancersFactor receptor 2Small cohort sizeAdjuvant therapyAdjuvant trastuzumabComorbid illnessesCardiac eventsAbsolute benefitSystemic Adjuvant Therapy for Stage I Breast Cancer
Pusztai L, Kelly C. Systemic Adjuvant Therapy for Stage I Breast Cancer. 2011, 269-281. DOI: 10.1007/978-94-007-0489-3_11.Peer-Reviewed Original ResearchStage I breast cancerI breast cancerMultivariable prediction modelBreast cancerAdjuvant therapyHuman epidermal growth factor 2 (HER2) receptor statusER-positive breast cancerSystemic adjuvant therapyCo-morbid illnessLymph node statusNottingham Prognostic IndexBetter risk stratificationIndependent prognostic factorBreast cancer biologyBreast cancer subtypesClinical factorsLymphovascular invasionPrognostic factorsReceptor statusRisk stratificationNode statusPrognostic indexPrognostic valueTumor sizeHistological grade