2024
Development and Validation of the RSClinN+ Tool to Predict Prognosis and Chemotherapy Benefit for Hormone Receptor-Positive, Node-Positive Breast Cancer.
Pusztai L, Hoag J, Albain K, Barlow W, Stemmer S, Meisner A, Hortobagyi G, Shak S, Rae J, Baehner R, Sharma P, Kalinsky K. Development and Validation of the RSClinN+ Tool to Predict Prognosis and Chemotherapy Benefit for Hormone Receptor-Positive, Node-Positive Breast Cancer. Journal Of Clinical Oncology 2024, jco2401507. PMID: 39621968, DOI: 10.1200/jco-24-01507.Peer-Reviewed Original ResearchChemoendocrine therapyRecurrence scorePostmenopausal womenClinicopathological factorsClinicopathological modelOncotype DX Breast Recurrence ScoreLymph node-positive breast cancerInvasive disease-free survivalNode-positive breast cancerHormone receptor-positiveNode-positive diseaseDisease-free survivalCox proportional hazards regression modelsIndividual recurrence riskProportional hazards regression modelsRisk estimatesHealth Service RegistryEstimation of prognosisHazards regression modelsPremenopausal patientsEndocrine therapyReceptor-positiveChemotherapy benefitMenopausal statusPatient-level dataCirculating tumor DNA fraction predicts residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer
Shan N, Gould B, Wang X, Bonora G, Blenman K, Foldi J, Campos G, Walsh M, Du P, Pusztai L. Circulating tumor DNA fraction predicts residual cancer burden post-neoadjuvant chemotherapy in triple negative breast cancer. The Journal Of Liquid Biopsy 2024, 6: 100168. DOI: 10.1016/j.jlb.2024.100168.Peer-Reviewed Original ResearchTriple negative breast cancerResidual cancer burdenCirculating tumor DNANegative breast cancerPathological responsePost-NACBreast cancerPlasma circulating tumor DNATriple negative breast cancer patientsResidual cancer burden scoreCirculating tumour DNA fractionPost-neoadjuvant chemotherapyPre-NAC samplesWeekly nab-paclitaxelTumor DNA methylation profilesTumor DNA fractionHot spot mutationsYouden's J statisticNab-paclitaxelPre-NACTumor variantsTumor DNATumor fractionClinical trialsDNA methylation profilesIdentification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial
Rediti M, Venet D, Joaquin Garcia A, Maetens M, Vincent D, Majjaj S, El-Abed S, Di Cosimo S, Ueno T, Izquierdo M, Piccart M, Pusztai L, Loi S, Salgado R, Viale G, Rothé F, Sotiriou C. Identification of HER2-positive breast cancer molecular subtypes with potential clinical implications in the ALTTO clinical trial. Nature Communications 2024, 15: 10402. PMID: 39613746, PMCID: PMC11607438, DOI: 10.1038/s41467-024-54621-3.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase III as TopicFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansMiddle AgedNeoplasm Recurrence, LocalPrognosisRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabTumor MicroenvironmentConceptsHER2-positive breast cancerMolecular subtypesBreast cancerRate of pathological complete responseSensitive to HER2-targeted therapiesClinical trialsRisk of distant recurrenceBreast cancer molecular subtypesPathological complete responseHER2-targeted therapyCancer molecular subtypesPotential clinical implicationsNeoALTTO trialDistant recurrenceComplete responseAdjuvant trastuzumabPrognostic/predictive valueHeterogeneous biologySurvival outcomesI-SPY2Clinical outcomesMicroenvironment featuresGene expression profilesExternal cohortTumorRare germline variants in cancer-relevant genes are associated with breast cancer risk in young women with high-risk family history
Rozenblit M, Qing T, Ye Y, Zhao H, Hofstatter E, Singh V, Reisenbichler E, Murray M, Pusztai L. Rare germline variants in cancer-relevant genes are associated with breast cancer risk in young women with high-risk family history. Breast Cancer Research And Treatment 2024, 1-6. PMID: 39602012, DOI: 10.1007/s10549-024-07560-y.Peer-Reviewed Original ResearchHigh-risk family historyFamily historyRare germline variantsCancer riskSNP-set kernel association testAssociated with breast cancer riskCancer casesContribution of family historyEarly-onset breast cancerCancer Prevention ClinicBreast cancerBreast cancer riskKernel association testBreast cancer casesCancer-predisposing genesGermline variantsGermline pathogenic variantsYoung womenPrevention clinicSKAT-OBurden testsPathogenic variantsExome sequencing dataAssociation TestLevel alterationsHormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers.
Rios-Hoyo A, Xiong K, Dai J, Yau C, Marczyk M, Garcia-Milian R, Wolf D, Huppert L, Nanda R, Hirst G, Cobain E, van 't Veer L, Esserman L, Pusztai L. Hormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers. Clinical Cancer Research 2024 PMID: 39561272, DOI: 10.1158/1078-0432.ccr-24-1553.Peer-Reviewed Original ResearchPathological complete responseEvent-free survivalBreast cancerHER2 negative breast cancerHormone receptor-positive/HER2-negativePathologic complete response ratePrognostic risk categoriesTN breast cancerNegative breast cancerGene set analysisExpression of cell cycleGene expression dataLow-risk subgroupsHigh-risk groupMammaPrint assayNeoadjuvant trialsComplete responseER statusResidual cancerPrognostic groupsClinical featuresI-SPY2Prognostic assaysExpression dataTreatment strategiesMulti-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer
Campbell M, Wolf D, Yau C, Brown-Swigart L, Wulfkuhle J, Gallagher I, Zhu Z, Bolen J, Vandenberg S, Hoyt C, Mori H, Borowsky A, Sit L, Perlmutter J, Asare S, Investigators I, Nanda R, Liu M, Yee D, DeMichele A, Hylton N, Pusztai L, Berry D, Hirst G, Petricoin E, Veer L, Esserman L. Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer. Cell Reports Medicine 2024, 101799. PMID: 39510069, DOI: 10.1016/j.xcrm.2024.101799.Peer-Reviewed Original ResearchImmune checkpoint blockadeI-SPY 2 TRIALPathological complete responseTumor microenvironmentBreast cancerAssociated with pathologic complete responseBreast cancer receptor subtypesNeoadjuvant immune checkpoint blockadePD-L1<sup>+</sup> cellsSpatial distribution of immune cellsDistribution of immune cellsEarly-stage breast cancerImmune checkpoint inhibitorsBiomarkers of responseImmune cell populationsImmune cell densityAssociated with responseImmune cell signalingCheckpoint blockadeCheckpoint inhibitorsComplete responsePretreatment biopsiesReceptor subtypesT cellsImmune cellsComparative Analysis of Ficoll-Hypaque and CytoLyt® Techniques for Blood Removal in Breast Cancer Malignant Effusions: Effects on RNA Quality and Sequencing Outcomes
Sura G, Tran K, Trevarton A, Marczyk M, Fu C, Du L, Qu J, Lau R, Tasto A, Gould R, Tinnirello A, Sinn B, Pusztai L, Hatzis C, Symmans W. Comparative Analysis of Ficoll-Hypaque and CytoLyt® Techniques for Blood Removal in Breast Cancer Malignant Effusions: Effects on RNA Quality and Sequencing Outcomes. Journal Of The American Society Of Cytopathology 2024 DOI: 10.1016/j.jasc.2024.11.001.Peer-Reviewed Original ResearchRNA integrity numberRNA qualityRNA-seqMeasurement of gene expressionRNA-seq analysisMetastatic breast cancerFicoll-Hypaque methodDensity gradient enrichmentSequence dataRead-basedVariant detectionMalignant effusionsCytospin slidesFresh frozen samplesRNA fragmentsTranscript abundanceSequencing outcomesSequencing methodsBreast cancerRNA sequencingFicoll-HypaqueUMI-basedGene expressionRNAMalignant effusion specimensPathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial
Huppert L, Wolf D, Yau C, Brown-Swigart L, Hirst G, Isaacs C, Pusztai L, Pohlmann P, DeMichele A, Shatsky R, Yee D, Thomas A, Nanda R, Perlmutter J, Heditsian D, Hylton N, Symmans F, Veer L, Esserman L, Rugo H. Pathologic complete response (pCR) rates for patients with HR+/HER2- high-risk, early-stage breast cancer (EBC) by clinical and molecular features in the phase II I-SPY2 clinical trial. Annals Of Oncology 2024 PMID: 39477071, DOI: 10.1016/j.annonc.2024.10.018.Peer-Reviewed Original ResearchDistant recurrence-free survivalEarly-stage breast cancerPathological complete responsePathologic complete response rateClinical/molecular featuresComplete responseER-positiveBreast cancerRate of pathological complete responseResponse to neoadjuvant chemotherapyRecurrence-free survivalI-SPY2 trialOptimal treatment selectionNeoadjuvant armER/PR statusLobular histologyNeoadjuvant chemotherapyIII diseaseImmune signaturesNegative diseaseOptimal therapyI-SPY2Excellent outcomesTreatment armsFollow-upMolecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations
Yasin F, Sokol E, Vasan N, Pavlick D, Huang R, Pelletier M, Levy M, Pusztai L, Lacy J, Zhang J, Ross J, Cecchini M. Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations. The Oncologist 2024, oyae259. PMID: 39401325, DOI: 10.1093/oncolo/oyae259.Peer-Reviewed Original ResearchAdvanced colorectal cancerPIK3CA mutationsColorectal cancerPI3K inhibitionPI3K inhibitorsBurden of colorectal cancerActivating mutationsResponse to PI3K inhibitionSensitive to PI3K inhibition.Foundation Medicine databaseMetastatic colorectal cancerClinically relevant mutationsMicrosatellite instability-highPI3K signalingTumor DNAPIK3CA variantsClinical carePIK3CA oncogeneClinical variablesE545KGenomic profilingPIK3CAE542KMedicine DatabasePatientsTrends in breast cancer–specific death by clinical stage at diagnoses between 2000 and 2017
Marczyk M, Kahn A, Silber A, Rosenblit M, Digiovanna M, Lustberg M, Pusztai L. Trends in breast cancer–specific death by clinical stage at diagnoses between 2000 and 2017. Journal Of The National Cancer Institute 2024, djae241. PMID: 39348186, DOI: 10.1093/jnci/djae241.Peer-Reviewed Original ResearchBreast cancer-specific deathCancer-specific deathBreast cancerStage IAll-cause mortalityTemporal trendsStage I/II breast cancerHormone receptor-positiveNode-negative cancersPrimary tumor typeStage I/II diseaseMetastatic breast cancerStage II cancerBilateral cancerIV cancerFemale sexIV diseaseReceptor-positiveExcellent prognosisII cancerClinical stageTumor typesTreated patientsStage IIICancerThe Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer
Dugo M, Huang C, Egle D, Bermejo B, Zamagni C, Seitz R, Nielsen T, Thill M, Antón-Torres A, Russo S, Ciruelos E, Schweitzer B, Ross D, Galbardi B, Greil R, Semiglazov V, Gyorffy B, Colleoni M, Kelly C, Mariani G, Del Mastro L, Blasi O, Callari M, Pusztai L, Valagussa P, Viale G, Gianni L, Bianchini G. The Immune-Related 27-Gene Signature DetermaIO Predicts Response to Neoadjuvant Atezolizumab plus Chemotherapy in Triple-Negative Breast Cancer. Clinical Cancer Research 2024, 30: of1-of10. PMID: 39308141, PMCID: PMC11528202, DOI: 10.1158/1078-0432.ccr-24-0149.Peer-Reviewed Original ResearchPathologic complete response ratePathological complete responseTriple-negative breast cancerRNA-seqI-SPY2Immuno-oncologyBreast cancerPatients treated with pembrolizumabTumor-infiltrating lymphocyte countsPublicly available microarray dataPretreatment core biopsiesImmune checkpoint therapyRNA-seq dataPer-protocol populationAvailable microarray dataI-SPY2 trialPDL1 protein expressionNeoadjuvant atezolizumabNeoadjuvant immunotherapyPlus chemotherapyCheckpoint therapyComplete responseTriple-negativeCore biopsyRT-qPCR dataOverall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer
Schmid P, Cortes J, Dent R, McArthur H, Pusztai L, Kümmel S, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Im S, Untch M, Fasching P, Mouret-Reynier M, Foukakis T, Ferreira M, Cardoso F, Zhou X, Karantza V, Tryfonidis K, Aktan G, O'Shaughnessy J. Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer. New England Journal Of Medicine 2024, 391: 1981-1991. PMID: 39282906, DOI: 10.1056/nejmoa2409932.Peer-Reviewed Original ResearchEarly-stage triple-negative breast cancerTriple-negative breast cancerPembrolizumab-chemotherapy groupPlacebo-chemotherapy groupCycles of pembrolizumabPathological complete responseEvent-free survivalOverall survivalBreast cancerAdjuvant pembrolizumabComplete responseSafety profile of pembrolizumabData cutoff dateUntreated stage IIPlatinum-containing chemotherapyMedian follow-upEstimate overall survivalSecondary end pointsEpirubicin-cyclophosphamideNeoadjuvant pembrolizumabNeoadjuvant therapyDoxorubicin-cyclophosphamideNeoadjuvant chemotherapyDefinitive surgeryPembrolizumabDatopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial
Khoury K, Meisel J, Yau C, Rugo H, Nanda R, Davidian M, Tsiatis B, Chien A, Wallace A, Arora M, Rozenblit M, Hershman D, Zimmer A, Clark A, Beckwith H, Elias A, Stringer-Reasor E, Boughey J, Nangia C, Vaklavas C, Omene C, Albain K, Kalinsky K, Isaacs C, Tseng J, Roussos Torres E, Thomas B, Thomas A, Sanford A, Balassanian R, Ewing C, Yeung K, Sauder C, Sanft T, Pusztai L, Trivedi M, Outhaythip A, Li W, Onishi N, Asare A, Beineke P, Norwood P, Brown-Swigart L, Hirst G, Matthews J, Moore B, Fraser Symmans W, Price E, Beedle C, Perlmutter J, Pohlmann P, Shatsky R, DeMichele A, Yee D, van ‘t Veer L, Hylton N, Esserman L. Datopotamab–deruxtecan in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial. Nature Medicine 2024, 1-9. PMID: 39277671, DOI: 10.1038/s41591-024-03266-2.Peer-Reviewed Original ResearchBreast cancerLikelihood of pathologic complete responseTreatment strategiesPathologic complete response rateEarly-stage breast cancerEarly surgical resectionTaxane-based regimenComplete response ratePathological complete responsePhase 2 trialBreast cancer subtypesEffective personalized treatmentHigh-risk stageMagnetic resonance imagingComplete responseDoxorubicin-cyclophosphamideNeoadjuvant treatmentSurgical resectionOcular eventsEfficacy analysisPrimary endpointTumor subtypesNew agentsCancer subtypesPatientsLBA4 Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study
Schmid P, Cortés J, Dent R, McArthur H, Pusztai L, Kummel S, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Im S, Untch M, Fasching P, Cardoso F, Zhao J, Zhou X, Tryfonidis K, Aktan G, O'Shaughnessy J. LBA4 Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Overall survival results from the phase III KEYNOTE-522 study. Annals Of Oncology 2024, 35: s1204-s1205. DOI: 10.1016/j.annonc.2024.08.2247.Peer-Reviewed Original ResearchPhosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer
Gunasekharan V, Lin H, Marczyk M, Rios-Hoyo A, Campos G, Shan N, Ahmed M, Umlauf S, Gareiss P, Raaisa R, Williams R, Cardone R, Siebel S, Kibbey R, Surovtseva Y, Pusztai L. Phosphoenolpyruvate carboxykinase-2 (PCK2) is a therapeutic target in triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 657-671. PMID: 39177932, DOI: 10.1007/s10549-024-07462-z.Peer-Reviewed Original ResearchMetabolic fluxTriple-negative breast cancerReduced metabolic fluxMDA-MB-231 cellsCell growth in vitroEnzyme assays in vitroMDA-MB-231Potential small molecule inhibitorsPyruvate carboxylaseGrowth in vitroSmall molecule inhibitorsIn silico screeningEnzyme assaysAssay in vitroEnzymatic assayCell lines in vitroEnzyme activityGrowth inhibitory activityBT-549Breast cancerIn vitro screeningBreast cell lines in vitroPhosphoenolpyruvateSignificant growth inhibitory activityLines in vitroAcademic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer
Kok M, Gielen R, Adams S, Lennerz J, Sharma P, Loibl S, Reardon E, Sonke G, Linn S, Delaloge S, Lacombe D, Robinson T, Badve S, Martin M, Balko J, Ignatiadis M, Curigliano G, Wolff A, Mittendorf E, Loi S, Pusztai L, Tolaney S, Salgado R. Academic Uphill Battle to Personalize Treatment for Patients With Stage II/III Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2024, 42: 3523-3529. PMID: 39038259, DOI: 10.1200/jco.24.00372.Peer-Reviewed Original ResearchPeripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer
Foldi J, Blenman K, Marczyk M, Gunasekharan V, Polanska A, Gee R, Davis M, Kahn A, Silber A, Pusztai L. Peripheral blood immune parameters, response, and adverse events after neoadjuvant chemotherapy plus durvalumab in early-stage triple-negative breast cancer. Breast Cancer Research And Treatment 2024, 208: 369-377. PMID: 39002068, DOI: 10.1007/s10549-024-07426-3.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerAssociated with pathological responsePathological complete responseNeoadjuvant chemotherapyCytokine levelsPathological responseAdverse eventsBreast cancerEarly-stage triple-negative breast cancerPatients treated with immune checkpoint inhibitorsB cell clonal expansionMeasured serum cytokine levelsImmune checkpoint inhibitorsGM-CSF levelsPeripheral blood cytokine levelsBlood cytokine levelsSerum cytokine levelsB cell receptorMagnetic bead panelBenjamini-Hochberg correctionSample of patientsImmunoSEQ platformCheckpoint inhibitorsComplete responseCompletion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023
Mariani M, Viale G, Galbardi B, Licata L, Bosi C, Dugo M, Notini G, Naldini M, Callari M, Criscitiello C, Pusztai L, Bianchini G. Completion Rate and Positive Results Reporting Among Immunotherapy Trials in Breast Cancer, 2004-2023. JAMA Network Open 2024, 7: e2423390. PMID: 39028669, PMCID: PMC11259908, DOI: 10.1001/jamanetworkopen.2024.23390.Peer-Reviewed Original ResearchConceptsCross-sectional studyPhase III trialsIII trialsBreast cancerImmunotherapy trialsLandscape of breast cancerPhase II studyPhase II trialPhase I trialSingle-center studySingle-center trialCancer immunotherapy trialsBreast cancer trialsPatient confidenceMain OutcomesFisher's exact testImmuno-oncology trialsTrial featuresProportion of trialsCompletion ratesAdjuvant settingPhase IIReport outcomesII trialPositive resultsNeoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study
Dent R, Cortés J, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Haiderali A, Jia L, Nguyen A, Pan W, O'Shaughnessy J, Schmid P. Neoadjuvant pembrolizumab plus chemotherapy/adjuvant pembrolizumab for early-stage triple-negative breast cancer: quality-of-life results from the randomized KEYNOTE-522 study. Journal Of The National Cancer Institute 2024, 116: 1654-1663. PMID: 38913881, PMCID: PMC11461162, DOI: 10.1093/jnci/djae129.Peer-Reviewed Original ResearchEarly-stage triple-negative breast cancerTriple-negative breast cancerLS mean changeBaseline to weekPatient-reported outcomesAdjuvant pembrolizumabBetween-group differencesKEYNOTE-522Neoadjuvant phaseAdjuvant phaseBreast cancerMean changePathological complete responseEvent-free survivalQuality-of-life resultsNeoadjuvant pembrolizumabPatient-reported outcome assessmentsComplete responseNeoadjuvant chemotherapyEORTC QLQ-30PembrolizumabQuality-of-lifeSecondary objectivesQLQ-30PlaceboEvaluation of large language models as a diagnostic aid for complex medical cases
Ríos-Hoyo A, Shan N, Li A, Pearson A, Pusztai L, Howard F. Evaluation of large language models as a diagnostic aid for complex medical cases. Frontiers In Medicine 2024, 11: 1380148. PMID: 38966538, PMCID: PMC11222590, DOI: 10.3389/fmed.2024.1380148.Peer-Reviewed Original ResearchClinical casesLanguage modelHospital case recordsConsecutive clinical casesDifferential diagnosis listComplex clinical casesDifferential diagnosisDiagnostic considerationsCase discussionDiagnostic aidCase recordsDiagnosisComplex medical casesDiagnosis listDifferential listMedical specialtiesMedical professionalsDiseaseIncidence