2023
Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer
Kyalwazi B, Yau C, Campbell M, Yoshimatsu T, Chien A, Wallace A, Forero-Torres A, Pusztai L, Ellis E, Albain K, Blaes A, Haley B, Boughey J, Elias A, Clark A, Isaacs C, Nanda R, Han H, Yung R, Tripathy D, Edmiston K, Viscusi R, Northfelt D, Khan Q, Asare S, Wilson A, Hirst G, Lu R, Symmans W, Yee D, DeMichele A, van ’t Veer L, Esserman L, Olopade O. Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer. JAMA Network Open 2023, 6: e2349646. PMID: 38153734, PMCID: PMC10755617, DOI: 10.1001/jamanetworkopen.2023.49646.Peer-Reviewed Original ResearchConceptsDistant recurrence-free survivalPathologic complete responseErbB2-negative tumorsWorse distant recurrence-free survivalEarly breast cancerWhite patientsBreast cancerBlack patientsGene expression signaturesReceptor subtypesStage II/III breast cancerHigh-risk early breast cancerCox proportional hazards regression modelHigh-risk breast cancerClinical trial end pointsProportional hazards regression modelsTumor receptor subtypeRetrospective cohort studyPrimary tumor sizeRecurrence-free survivalTrial end pointsBreast cancer outcomesLong-term outcomesHazards regression modelsExpression signaturesPembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer
Takahashi M, Cortés J, Dent R, Pusztai L, McArthur H, Kümmel S, Denkert C, Park Y, Im S, Ahn J, Mukai H, Huang C, Chen S, Kim M, Jia L, Li X, Tryfonidis K, Karantza V, Iwata H, Schmid P. Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer. JAMA Network Open 2023, 6: e2342107. PMID: 37966841, PMCID: PMC10652156, DOI: 10.1001/jamanetworkopen.2023.42107.Peer-Reviewed Original ResearchConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalPathologic complete responseChemotherapy groupNeoadjuvant chemotherapyBreast cancerNeoadjuvant pembrolizumabDefinitive surgeryComplete responseMAIN OUTCOMEEastern Cooperative Oncology Group performance statusCell death ligand 1 (PD-L1) statusDeath ligand 1 (PD-L1) statusTreatment-related adverse eventsNonmetastatic triple-negative breast cancerCycles of pembrolizumabPembrolizumab Plus ChemotherapyTumor PD-L1Unacceptable toxic effectsPD-L1 statusOverall survival analysisAdjuvant pembrolizumabEFS eventsEFS ratesTreatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials?
Chehayeb R, Kahn A, Pusztai L. Treatment efficacy score: a better surrogate for arm-level survival differences in neoadjuvant breast cancer trials? Future Oncology 2023, 19: 1945-1951. PMID: 37767612, DOI: 10.2217/fon-2022-1203.Peer-Reviewed Original ResearchExcellent long-term survivalNeoadjuvant breast cancer trialsResidual cancer burden scorePathologic complete responseBreast cancer trialsLong-term survivalNeoadjuvant chemotherapyPathologic responseComplete responseSurvival improvementBurden scoreResidual diseaseTrial armsSurvival differencesCancer trialsBreast cancerTreatment efficacyStage IIGood surrogateEfficacy scoresTrialsSurvivalScoresRate differencesChemotherapyStandardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP
Litton J, Regan M, Pusztai L, Rugo H, Tolaney S, Garrett-Mayer E, Amiri-Kordestani L, Basho R, Best A, Boileau J, Denkert C, Foster J, Harbeck N, Jacene H, King T, Mason G, O'Sullivan C, Prowell T, Richardson A, Sepulveda K, Smith M, Tjoe J, Turashvili G, Woodward W, Butler L, Schwartz E, Korde L. Standardized Definitions for Efficacy End Points in Neoadjuvant Breast Cancer Clinical Trials: NeoSTEEP. Journal Of Clinical Oncology 2023, 41: 4433-4442. PMID: 37433103, PMCID: PMC10522109, DOI: 10.1200/jco.23.00435.Peer-Reviewed Original ResearchConceptsSecondary end pointsPathologic complete responseClinical trialsEnd pointStandardized definitionsHormone receptor-positive diseaseCurative-intent surgeryNeoadjuvant clinical trialsPathologic nodal evaluationResidual invasive cancerEfficacy end pointReceptor-positive diseaseBreast cancer clinical trialsResidual cancer burdenAlternative end pointsTrial end pointsRegional lymph nodesCancer end pointsCross-trial comparisonsSurvival end pointsEnd point definitionsCancer clinical trialsDrug Administration (FDA) regulatory considerationsEfficacy outcomesComplete responseCorrelation of HER2 low status in I-SPY2 with molecular subtype, response, and survival.
Rugo H, Wolf D, Yau C, Petricoin E, Pohlmann P, Pusztai L, Symmans W, Borowsky A, Finestone S, Yee D, Hylton N, van 't Veer L, Esserman L, DeMichele A. Correlation of HER2 low status in I-SPY2 with molecular subtype, response, and survival. Journal Of Clinical Oncology 2023, 41: 514-514. DOI: 10.1200/jco.2023.41.16_suppl.514.Peer-Reviewed Original ResearchDistant recurrence-free survivalPathologic complete responseBreast cancerFisher's exact testExact testMolecular subtypesHER2-negative breast cancerHigh-risk breast cancerRisk breast cancerMetastatic breast cancerRecurrence-free survivalTN breast cancerRecurrence-free survival dataCox proportional hazardsHER2 gene amplificationI-SPY2TN diseaseFree survivalOverall survivalComplete responseHazard ratioTrastuzumab deruxtecanEndocrine sensitivityT-DXdTreatment armsImage analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial
Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Liu Y, Wang L, Wei W, Pusztai L, Blenman K. Image analysis-based tumor infiltrating lymphocytes measurement predicts breast cancer pathologic complete response in SWOG S0800 neoadjuvant chemotherapy trial. Npj Breast Cancer 2023, 9: 38. PMID: 37179362, PMCID: PMC10182981, DOI: 10.1038/s41523-023-00535-0.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerComplete responseTIL scoreBreast Cancer Pathologic Complete ResponseTumor-infiltrating lymphocyte scoresEvent-free survivalNeoadjuvant chemotherapy trialsLymphocyte measurementsLymphocyte scoreNeoadjuvant chemotherapyChemotherapy trialsMean pretreatmentResidual diseaseTIL quantificationPredictive valuePretreatment samplesResponse discriminationScoresStrong positive correlationPositive correlation
2022
Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements.
Blenman K, Fanucci K, Bai Y, Pelekanou V, Nahleh Z, Shafi S, Burela S, Barlow W, Sharma P, Thompson A, Godwin A, Rimm D, Hortobagyi G, Pusztai L. Prediction of pathologic complete response to neoadjuvant chemotherapy in breast cancer (SWOG S0800) using image analysis-based tumor infiltrating lymphocyte measurements. Journal Of Clinical Oncology 2022, 40: 594-594. DOI: 10.1200/jco.2022.40.16_suppl.594.Peer-Reviewed Original ResearchPathologic complete responseBreast cancerNeoadjuvant chemotherapyComplete responseTIL scoreResidual diseaseResponse predictive markersBetter EFSBevacizumab benefitLymphocyte measurementsTIL assessmentFree survivalPredictive markerTIL quantificationInternational guidelinesPretreatment samplesLogistic regressionCancerOutcome discriminationChemotherapyScoresContinuous scoresTumorsClinical adoptionStrong positive correlationPredictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer.
Blenman KRM, Marczyk M, Karn T, Qing T, Li X, Gunasekharan V, Yaghoobi V, Bai Y, Ibrahim EY, Park T, Silber A, Wolf DM, Reisenbichler E, Denkert C, Sinn BV, Rozenblit M, Foldi J, Rimm DL, Loibl S, Pusztai L. Predictive Markers of Response to Neoadjuvant Durvalumab with Nab-Paclitaxel and Dose-Dense Doxorubicin/Cyclophosphamide in Basal-Like Triple-Negative Breast Cancer. Clinical Cancer Research 2022, 28: 2587-2597. PMID: 35377948, PMCID: PMC9464605, DOI: 10.1158/1078-0432.ccr-21-3215.Peer-Reviewed Original ResearchConceptsBasal-like triple-negative breast cancerPathologic complete responseResidual diseaseNeoadjuvant durvalumabDNA damage repairSomatic mutationsBreast cancerWnt/β-cateninHigh expressionTriple-negative breast cancerBasal-Like TripleDoxorubicin/cyclophosphamideDNA repairTumor mutation burdenRNA sequencingEpithelial-mesenchymal transitionFive-gene signatureB-cell markersCancer driversEnrichment analysisNegative breast cancerDamage repairGene expressionJAK-STATCell cycle
2021
Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer
Symmans WF, Yau C, Chen YY, Balassanian R, Klein ME, Pusztai L, Nanda R, Parker BA, Datnow B, Krings G, Wei S, Feldman MD, Duan X, Chen B, Sattar H, Khazai L, Zeck JC, Sams S, Mhawech-Fauceglia P, Rendi M, Sahoo S, Ocal IT, Fan F, LeBeau LG, Vinh T, Troxell ML, Chien AJ, Wallace AM, Forero-Torres A, Ellis E, Albain KS, Murthy RK, Boughey JC, Liu MC, Haley BB, Elias AD, Clark AS, Kemmer K, Isaacs C, Lang JE, Han HS, Edmiston K, Viscusi RK, Northfelt DW, Khan QJ, Leyland-Jones B, Venters SJ, Shad S, Matthews JB, Asare SM, Buxton M, Asare AL, Rugo HS, Schwab RB, Helsten T, Hylton NM, van ’t Veer L, Perlmutter J, DeMichele AM, Yee D, Berry DA, Esserman LJ. Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer. JAMA Oncology 2021, 7: 1654-1663. PMID: 34529000, PMCID: PMC8446908, DOI: 10.1001/jamaoncol.2021.3690.Peer-Reviewed Original ResearchConceptsEvent-free survivalPathologic complete responseResidual cancer burdenInvestigational agentsInvestigational treatmentBreast cancerInterpretation of efficacyNeoadjuvant treatmentCancer burdenClinical trialsImproved event-free survivalNeoadjuvant breast cancer trialsStage 2/3 breast cancerHigh-risk breast cancerHormone receptorsI-SPY2 trialSecondary end pointsBreast cancer trialsEffective neoadjuvant treatmentI-SPY2Neoadjuvant paclitaxelNeoadjuvant trialsComplete responseEarly recurrencePrognostic significanceCopy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial.
Venet D, Rediti M, Maetens M, Fumagalli D, Brown DN, Majjaj S, Salgado R, Pusztai L, Harbeck N, El-Abed S, Wang Y, Saura C, Gomez H, Semiglazov VF, de Azambuja E, Huober J, Nuciforo P, Di Cosimo S, Piccart M, Loi S, Rothé F, Sotiriou C. Copy number aberration analysis to predict response to neoadjuvant anti-HER2 therapy: results from the NeoALTTO phase III clinical trial. Clinical Cancer Research 2021, 27: clincanres.1317.2021. PMID: 34321278, DOI: 10.1158/1078-0432.ccr-21-1317.Peer-Reviewed Original ResearchConceptsPathologic complete responseNeoALTTO trialCopy number aberrationsBreast cancerHER2-positive early-stage breast cancerEstrogen receptor-positive subgroupNeoadjuvant anti-HER2 therapyEarly-stage breast cancerHER2-positive breast cancerPhase III clinical trialsAnti-HER2 therapyAnti-HER2 agentsPredictors of responseReceptor-positive subgroupNumber aberration analysisCopy number levelsWarrants further investigationHeterogeneity of responseComplete responseSurvival outcomesWhole cohortClinical trialsImmune processesPatientsSignificant associationOptimal 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 estimatesNeoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
Foldi J, Silber A, Reisenbichler E, Singh K, Fischbach N, Persico J, Adelson K, Katoch A, Horowitz N, Lannin D, Chagpar A, Park T, Marczyk M, Frederick C, Burrello T, Ibrahim E, Qing T, Bai Y, Blenman K, Rimm DL, Pusztai L. Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2021, 7: 9. PMID: 33558513, PMCID: PMC7870853, DOI: 10.1038/s41523-021-00219-7.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesWeekly nab-paclitaxelTriple-negative breast cancerPD-L1Nab-paclitaxelAdverse eventsBreast cancerGrade 3/4 treatment-related adverse eventsPhase I/II trialGrade 3/4 adverse eventsTreatment-related adverse eventsDoxorubicin/cyclophosphamidePhase II studyGuillain-Barre syndromeMononuclear inflammatory cellsPathologic complete responseTumor-infiltrating lymphocytesTumor cell stainingEvaluable patientsNeoadjuvant durvalumabSP263 antibodyII trialNeoadjuvant chemotherapyNeoadjuvant therapyPrimary endpoint
2020
Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer
Kunst N, Wang SY, Hood A, Mougalian SS, DiGiovanna MP, Adelson K, Pusztai L. Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer. JAMA Network Open 2020, 3: e2027074. PMID: 33226431, PMCID: PMC7684449, DOI: 10.1001/jamanetworkopen.2020.27074.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicBreast NeoplasmsCase-Control StudiesCost-Benefit AnalysisCross-Linking ReagentsDrug Therapy, CombinationFemaleHumansImmunosuppressive AgentsMiddle AgedNeoadjuvant TherapyPaclitaxelQuality-Adjusted Life YearsReceptor, ErbB-2TrastuzumabTubulin ModulatorsUnited StatesConceptsErbB2-positive breast cancerAdjuvant treatment strategiesAdjuvant T-DM1Pathologic complete responseT-DM1Treatment strategiesBreast cancerKATHERINE trialResidual diseaseNeoadjuvant regimenHigher health benefitsHealth care payer perspectiveAdjuvant trastuzumab emtansineAnthracycline/cyclophosphamideDifferent adjuvant therapiesFlatiron Health databaseIncremental cost-effectiveness ratioNeoadjuvant treatment optionsHealth benefitsPositive breast cancerCare payer perspectiveCost-effectiveness ratioBase-case analysisDecision analytic modelH. PatientsAssociation of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer
Consortium I, Yee D, DeMichele A, Yau C, Isaacs C, Symmans W, Albain K, Chen Y, Krings G, Wei S, Harada S, Datnow B, Fadare O, Klein M, Pambuccian S, Chen B, Adamson K, Sams S, Mhawech-Fauceglia P, Magliocco A, Feldman M, Rendi M, Sattar H, Zeck J, Ocal I, Tawfik O, LeBeau L, Sahoo S, Vinh T, Chien A, Forero-Torres A, Stringer-Reasor E, Wallace A, Pusztai L, Boughey J, Ellis E, Elias A, Lu J, Lang J, Han H, Clark A, Nanda R, Northfelt D, Khan Q, Viscusi R, Euhus D, Edmiston K, Chui S, Kemmer K, Park J, Liu M, Olopade O, Leyland-Jones B, Tripathy D, Moulder S, Rugo H, Schwab R, Lo S, Helsten T, Beckwith H, Haugen P, Hylton N, Veer L, Perlmutter J, Melisko M, Wilson A, Peterson G, Asare A, Buxton M, Paoloni M, Clennell J, Hirst G, Singhrao R, Steeg K, Matthews J, Asare S, Sanil A, Berry S, Esserman L, Berry D. Association of Event-Free and Distant Recurrence–Free Survival With Individual-Level Pathologic Complete Response in Neoadjuvant Treatment of Stages 2 and 3 Breast Cancer. JAMA Oncology 2020, 6: 1355-1362. PMID: 32701140, PMCID: PMC7378873, DOI: 10.1001/jamaoncol.2020.2535.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsCyclophosphamideDisease-Free SurvivalDoxorubicinFemaleHumansMiddle AgedNeoadjuvant TherapyNeoplasm Recurrence, LocalProgression-Free SurvivalProportional Hazards ModelsReceptor, ErbB-2TaxoidsTrastuzumabTreatment OutcomeConceptsDistant recurrence-free survivalPathologic complete responseEvent-free survivalI-SPY2 trialRecurrence-free survivalLong-term outcomesBreast cancerComplete responseNeoadjuvant therapyPlatform trialsMolecular subtypesHigh-risk operable breast cancerThree-year event-free survivalHormone receptorsClinical stage 2Phase 3 confirmatory trialOperable breast cancerSubpopulation of womenNovel therapeutic combinationsStage 2Investigational regimensNeoadjuvant treatmentPrior surgeryTaxane treatmentStandard therapyA phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL.
Loi S, McArthur H, Harbeck N, Pusztai L, Delaloge S, Letrent K, Chen T, Li B, Tatsuoka K, Zardavas D, Curigliano G. A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2- primary breast cancer: CheckMate 7FL. Journal Of Clinical Oncology 2020, 38: tps604-tps604. DOI: 10.1200/jco.2020.38.15_suppl.tps604.Peer-Reviewed Original ResearchAdjuvant endocrine therapyPathologic complete responsePrimary breast cancerEndocrine therapyNeoadjuvant chemotherapyBreast cancerNeoadjuvant phaseER expressionGlobal phase 3 studyDeath ligand 1 (PD-L1) expressionLong-term clinical outcomesAdequate organ functionDeath-1 (PD-1) inhibitionLow ER expressionAxillary nodal statusDisease-free survivalEvent-free survivalLigand 1 expressionPhase III trialsResidual cancer burdenPhase 3 studyOverall response rateRisk of relapseValid surrogate endpointQuality of lifeEffect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer
Nanda R, Liu MC, Yau C, Shatsky R, Pusztai L, Wallace A, Chien AJ, Forero-Torres A, Ellis E, Han H, Clark A, Albain K, Boughey JC, Jaskowiak NT, Elias A, Isaacs C, Kemmer K, Helsten T, Majure M, Stringer-Reasor E, Parker C, Lee MC, Haddad T, Cohen RN, Asare S, Wilson A, Hirst GL, Singhrao R, Steeg K, Asare A, Matthews JB, Berry S, Sanil A, Schwab R, Symmans WF, van ‘t Veer L, Yee D, DeMichele A, Hylton NM, Melisko M, Perlmutter J, Rugo HS, Berry DA, Esserman LJ. Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer. JAMA Oncology 2020, 6: 676-684. PMID: 32053137, PMCID: PMC7058271, DOI: 10.1001/jamaoncol.2019.6650.Peer-Reviewed Original ResearchConceptsEarly-stage breast cancerPathologic complete responseNeoadjuvant chemotherapyPhase 3 trialResidual cancer burdenStandard neoadjuvant chemotherapyBreast cancerComplete responseInvestigational armStage II/III breast cancerHigher event-free survival rateERBB2-negative breast cancerEvent-free survival rateAnthracycline-based neoadjuvant chemotherapyDistant recurrence-free survivalEnd pointTriple-negative breast cancerCycles of pembrolizumabEffect of pembrolizumabImmune-related endocrinopathiesNeoadjuvant clinical trialsTriple-negative cohortPrimary end pointSecondary end pointsRecurrence-free survival
2019
Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial
Li X, Warren S, Pelekanou V, Wali V, Cesano A, Liu M, Danaher P, Elliott N, Nahleh ZA, Hayes DF, Hortobagyi GN, Barlow WE, Hatzis C, Pusztai L. Immune profiling of pre- and post-treatment breast cancer tissues from the SWOG S0800 neoadjuvant trial. Journal For ImmunoTherapy Of Cancer 2019, 7: 88. PMID: 30967156, PMCID: PMC6457012, DOI: 10.1186/s40425-019-0563-7.Peer-Reviewed Original ResearchConceptsPathologic complete responseResidual diseaseTIL countGene expression levelsHigh expressionCellular stressNeoadjuvant chemotherapyImmune genesImmune-related genesStromal genesImmune functionImmune microenvironment changesMost immune functionsGenesCell typesPD-L1 protein expressionStem cellsHigher TIL countsPD-L1 expressionExpression levelsPrimary breast cancerT-cell markersImmune cell typesProtein expressionStromal functionImmune microenvironment of triple-negative breast cancer in African-American and Caucasian women
O’Meara T, Safonov A, Casadevall D, Qing T, Silber A, Killelea B, Hatzis C, Pusztai L. Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women. Breast Cancer Research And Treatment 2019, 175: 247-259. PMID: 30725384, PMCID: PMC6666415, DOI: 10.1007/s10549-019-05156-5.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerCaucasian breast cancersER-positive cancersBreast cancerTIL countImmune microenvironmentCaucasian patientsMolecular subtypesAA TNBCHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Pathologic complete responseGrowth factor receptor 2Immune cell distributionImmune cell populationsCancer Genome Atlas (TCGA) databaseConsistent racial differencesFactor receptor 2Immune gene expressionImmune attenuationNeoadjuvant chemotherapyLymphocyte countLymphocyte infiltrationComplete responseTNBC cases
2018
Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Powles RL, Redmond D, Sotiriou C, Loi S, Fumagalli D, Nuciforo P, Harbeck N, de Azambuja E, Sarp S, Di Cosimo S, Huober J, Baselga J, Piccart-Gebhart M, Elemento O, Pusztai L, Hatzis C. Association of T-Cell Receptor Repertoire Use With Response to Combined Trastuzumab-Lapatinib Treatment of HER2-Positive Breast Cancer: Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2018, 4: e181564-e181564. PMID: 29902299, PMCID: PMC6224305, DOI: 10.1001/jamaoncol.2018.1564.Peer-Reviewed Original ResearchConceptsDual HER2 blockadeImmune gene signaturesPathologic complete responseDual HER2HER2 blockadeNeoALTTO trialDual anti-HER2 blockadeHigher immune gene expressionTrastuzumab Treatment Optimisation (ALTTO) trialHER2-positive breast cancerGene signatureAnti-HER2 blockadeHigher useHER2-positive patientsMultivariable logistic regressionRandomized clinical trialsGood responseHigh rateImmune gene expressionNeoadjuvant lapatinibTherapy armIdentifies patientsNeoadjuvant therapyComplete responseGene expression signaturesTumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial
Pelekanou V, Barlow WE, Nahleh Z, Wasserman B, Lo YC, von Wahlde MK, Hayes D, Hortobagyi GN, Gralow J, Tripathy D, Porter P, Szekely B, Hatzis C, Rimm DL, Pusztai L. Tumor infiltrating lymphocytes and PD-L1 expression in pre- and post-treatment breast cancers in the SWOG S0800 Phase II neoadjuvant chemotherapy trial. Molecular Cancer Therapeutics 2018, 17: molcanther.1005.2017. PMID: 29588392, PMCID: PMC6548451, DOI: 10.1158/1535-7163.mct-17-1005.Peer-Reviewed Original ResearchConceptsPD-L1 expressionPathologic complete responseTIL countPosttreatment tissuePD-L1Estrogen receptorImmune checkpoint inhibitor therapyPD-L1 positivity rateTumor-infiltrating lymphocyte countsDoxorubicin/cyclophosphamideCheckpoint inhibitor therapyPD-L1 levelsMol Cancer TherNab-paclitaxelLymphocyte countResidual cancerComplete responseER statusImmune changesInhibitor therapyCox regressionPatient populationControl armClinical trialsPositivity rate