2024
Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆
Pusztai L, Denkert C, O’Shaughnessy J, Cortes J, Dent R, McArthur H, Kümmel S, Bergh J, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Zhu Y, Pan W, Tryfonidis K, Schmid P. Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522☆. Annals Of Oncology 2024, 35: 429-436. PMID: 38369015, DOI: 10.1016/j.annonc.2024.02.002.Peer-Reviewed Original ResearchTriple-negative breast cancerEvent-free survivalPathological complete responseResidual cancer burdenEarly-stage triple-negative breast cancerEvent-free survival eventsPembrolizumab groupRCB-2KEYNOTE-522Neoadjuvant pembrolizumabRCB-0Central nervous system recurrenceCancer burdenCycles of paclitaxelIncreased pCR ratePembrolizumab to chemotherapyCycles of doxorubicinCox regression modelsRCB-1Adjuvant pembrolizumabDistant recurrencePCR rateResidual diseaseSystemic recurrenceComplete response
2023
356P Prognostic value of the residual cancer burden after neoadjuvant chemotherapy for invasive lobular breast cancer: An international pooled cohort study
Gottipati S, Earl H, Yau C, Cameron D, Abraham J, Hayward L, Reyal F, Osdoit M, Sonke G, Wesseling J, Boughey J, Goetz M, DeMichele A, Pusztai L, Sharma P, Jimenez M, Cobo S, Del Monte-Millan M, Symmans F, Mukhtar R. 356P Prognostic value of the residual cancer burden after neoadjuvant chemotherapy for invasive lobular breast cancer: An international pooled cohort study. Annals Of Oncology 2023, 34: s325-s326. DOI: 10.1016/j.annonc.2023.09.535.Peer-Reviewed Original ResearchStandardized 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 response
2022
Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522.
Pusztai L, Denkert C, O'Shaughnessy J, Cortes J, Dent R, McArthur H, Kuemmel S, Bergh J, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Zhu Y, Pan W, Tryfonidis K, Schmid P. Event-free survival by residual cancer burden after neoadjuvant pembrolizumab + chemotherapy versus placebo + chemotherapy for early TNBC: Exploratory analysis from KEYNOTE-522. Journal Of Clinical Oncology 2022, 40: 503-503. DOI: 10.1200/jco.2022.40.16_suppl.503.Peer-Reviewed Original Research
2021
Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients
Yau C, Osdoit M, van der Noordaa M, Shad S, Wei J, de Croze D, Hamy AS, Laé M, Reyal F, Sonke GS, Steenbruggen TG, van Seijen M, Wesseling J, Martín M, del Monte-Millán M, López-Tarruella S, Consortium I, Adamson K, Albain K, Asare A, Asare S, Balassanian R, Beckwith H, Berry S, Berry D, Boughey J, Buxton M, Chen Y, Chen B, Chien A, Chui S, Clark A, Clennell J, Datnow B, DeMichele A, Duan X, Edmiston K, Elias A, Ellis E, Esserman L, Euhus D, Fadare O, Fan F, Feldman M, Forero-Torres A, Haley B, Han H, Harada S, Haugen P, Helsten T, Hirst G, Hylton N, Isaacs C, Kemmer K, Khan Q, Khazai L, Klein M, Krings G, Lang J, LeBeau L, Leyland-Jones B, Liu M, Lo S, Lu J, Magliocco A, Matthews J, Melisko M, Mhawech-Fauceglia P, Moulder S, Murthy R, Nanda R, Northfelt D, Ocal I, Olopade O, Pambuccian S, Paoloni M, Park J, Parker B, Perlmutter J, Peterson G, Pusztai L, Rendi M, Rugo H, Sahoo S, Sams S, Sanil A, Sattar H, Schwab R, Singhrao R, Steeg K, Stringer-Reasor E, Symmans W, Tawfik O, Tripathy D, Troxell M, Veer L, Venters S, Vinh T, Viscusi R, Wallace A, Wei S, Wilson A, Yau C, Yee D, Zeck J, Boughey J, Goetz M, Hoskin T, Gould R, Valero V, Edge S, Abraham J, Bartlett J, Caldas C, Dunn J, Earl H, Hayward L, Hiller L, Provenzano E, Sammut S, Thomas J, Cameron D, Graham A, Hall P, Mackintosh L, Fan F, Godwin A, Schwensen K, Sharma P, DeMichele A, Cole K, Pusztai L, Kim M, van 't Veer L, Esserman L, Symmans W. Residual cancer burden after neoadjuvant chemotherapy and long-term survival outcomes in breast cancer: a multicentre pooled analysis of 5161 patients. The Lancet Oncology 2021, 23: 149-160. PMID: 34902335, PMCID: PMC9455620, DOI: 10.1016/s1470-2045(21)00589-1.Peer-Reviewed Original ResearchConceptsResidual cancer burdenEvent-free survivalRCB scoreHER2-positive groupNeoadjuvant chemotherapyBreast cancer subtypesBreast cancerHazard ratioCancer subtypesNodal statusCancer burdenT categoryEvent-free survival eventsPooled patient-level analysisLong-term survival outcomesPractice settingsWorse event-free survivalClinical T categoryHigher RCB scoresStandard pathology reportingHER2-negative patientsHormone receptor statusHER2-negative groupLong-term prognosisPrimary stage IAssessment 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 significancePredicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy
Du L, Yau C, Brown-Swigart L, Gould R, Krings G, Hirst G, Bedrosian I, Layman R, Carter J, Klein M, Venters S, Shad S, van der Noordaa M, Chien A, Haddad T, Isaacs C, Pusztai L, Albain K, Nanda R, Tripathy D, Liu M, Boughey J, Schwab R, Hylton N, DeMichele A, Perlmutter J, Yee D, Berry D, Veer L, Valero V, Esserman L, Symmans W. Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2−) breast cancer before chemo-endocrine therapy. Annals Of Oncology 2021, 32: 642-651. PMID: 33617937, DOI: 10.1016/j.annonc.2021.02.011.Peer-Reviewed Original ResearchConceptsResidual cancer burdenI-SPY2 trialIndependent prognostic informationPrognostic informationBreast cancerPrognostic signaturePre-treatment tumor biopsiesHER2-negative breast cancerStage IIDistant relapse-free survivalMultivariate Cox regression modelHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Chemo-endocrine therapyEndocrine-based treatmentAdjuvant endocrine therapyGrowth factor receptor 2Primary outcome measureRelapse-free survivalSimilar prognostic informationCox regression modelMolecular prognostic signaturesNegative breast cancerFactor receptor 2MDACC cohort
2020
A 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
2017
Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype
Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, Walls A, Bousamra A, Ramineni M, Sinn B, Hunt K, Buchholz TA, Valero V, Buzdar AU, Yang W, Brewster AM, Moulder S, Pusztai L, Hatzis C, Hortobagyi GN. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. Journal Of Clinical Oncology 2017, 35: jco.2015.63.101. PMID: 28135148, PMCID: PMC5455352, DOI: 10.1200/jco.2015.63.1010.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCyclophosphamideDisease-Free SurvivalDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPaclitaxelPhenotypePrognosisProspective StudiesReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRisk AssessmentSurvival RateTime FactorsTrastuzumabTumor BurdenConceptsResidual cancer burdenPhenotypic subsetsNeoadjuvant chemotherapyValidation cohortPrognostic riskCancer burdenRCB classBreast cancerRCB indexRelapse-free survival estimatesRelapse-free survival rateHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Hormone receptorsOriginal development cohortGrowth factor receptor 2Clinical-pathologic variablesKaplan-Meier analysisLong-term prognosisLog-rank testIndependent validation cohortBreast cancer subtypesLong-term survivalFactor receptor 2Concurrent trastuzumab
2008
Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab
Peintinger F, Buzdar AU, Kuerer HM, Mejia JA, Hatzis C, Gonzalez-Angulo AM, Pusztai L, Esteva FJ, Dawood SS, Green MC, Hortobagyi GN, Symmans WF. Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Annals Of Oncology 2008, 19: 2020-2025. PMID: 18667396, PMCID: PMC2733116, DOI: 10.1093/annonc/mdn427.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicCyclophosphamideDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualNeoplasms, Hormone-DependentPaclitaxelRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTrastuzumabConceptsHER2-positive breast cancerHormone receptor statusPathologic complete responseResidual cancer burdenPathologic responseBreast cancerNeoadjuvant chemotherapyReceptor statusExtensive residual diseaseHR-negative cancerHR-positive cancersPathologic response rateAddition of trastuzumabNeo-adjuvant chemotherapyStandard neoadjuvant chemotherapyFEC chemotherapyHR-/HER2Pathologic reviewComplete responseLymph nodesCancer burdenResidual diseasePrimary tumorChemotherapyResponse ratePreoperative Systemic Chemotherapy and Pathologic Assessment of Response
Pusztai L. Preoperative Systemic Chemotherapy and Pathologic Assessment of Response. Pathology & Oncology Research 2008, 14: 169-171. PMID: 18553157, DOI: 10.1007/s12253-008-9070-8.Peer-Reviewed Original ResearchConceptsPathologic complete responsePreoperative systemic chemotherapyResidual cancer burdenResidual diseaseNeoadjuvant treatmentSystemic chemotherapyAxillary nodal burdenNeoadjuvant clinical trialsRoutine therapeutic modalityAdvanced breast cancerPrimary tumor dimensionsTranslational research modelRoutine diagnostic practiceNodal burdenPathologic responseComplete responsePathologic assessmentPrognostic distinctionResistant diseaseCancer burdenAdverse outcomesTumor bedClinical trialsPathologic informationBreast cancerPrognostic value of residual cancer burden after neoadjuvant taxane-anthracycline chemotherapy in phenotypic subsets of breast cancer
Hubbard R, Peintinger F, Liedtke C, Hatzis C, Kuerer H, Valero V, Buzdar A, Hortobagyi G, Pusztai L, Symmans W. Prognostic value of residual cancer burden after neoadjuvant taxane-anthracycline chemotherapy in phenotypic subsets of breast cancer. Journal Of Clinical Oncology 2008, 26: 544-544. DOI: 10.1200/jco.2008.26.15_suppl.544.Peer-Reviewed Original ResearchResidual cancer burdenCancer burdenPrognostic valueBreast cancerPhenotypic subsetsChemotherapyCancer
2007
Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy
Symmans WF, Peintinger F, Hatzis C, Rajan R, Kuerer H, Valero V, Assad L, Poniecka A, Hennessy B, Green M, Buzdar AU, Singletary SE, Hortobagyi GN, Pusztai L. Measurement of Residual Breast Cancer Burden to Predict Survival After Neoadjuvant Chemotherapy. Journal Of Clinical Oncology 2007, 25: 4414-4422. PMID: 17785706, DOI: 10.1200/jco.2007.10.6823.Peer-Reviewed Original ResearchConceptsDistant relapse-free survivalResidual cancer burdenHormone receptor statusNeoadjuvant chemotherapyHormone therapyPathologic responseReceptor statusCancer burdenResidual diseasePathologic American Joint CommitteeMultivariate Cox regression analysisAdjuvant hormone therapyBreast cancer burdenDifferent treatment cohortsPretreatment clinical stageAmerican Joint CommitteeCox regression analysisRelapse-free survivalSequential paclitaxelDistant relapseSame prognosisComplete responseNodal metastasisTreatment cohortsClinical stageThirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer
Peintinger F, Anderson K, Mazouni C, Kuerer HM, Hatzis C, Lin F, Hortobagyi GN, Symmans WF, Pusztai L. Thirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer. Clinical Cancer Research 2007, 13: 4078-4082. PMID: 17634532, DOI: 10.1158/1078-0432.ccr-06-2600.Peer-Reviewed Original ResearchConceptsResidual cancer burdenRCB 0RCB scoreRCB-IIICancer burdenPharmacogenomic testsRCB-IIPreoperative chemotherapyRCB classBreast cancerChemotherapy-resistant diseaseLymph node featuresPathologic reviewPathologic responseResidual tumorStage IPatientsIII groupChemotherapyI groupGene expression profilingCategorical variablesMean scoreScoresCancerThe impact of hormone receptor status on pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy with or without trastuzumab
Peintinger F, Buzdar A, Kuerer H, Gonzalez-Angulo A, Hatzis C, Pusztai L, Esteva F, Green M, Hortobagyi G, Symmans W. The impact of hormone receptor status on pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy with or without trastuzumab. Journal Of Clinical Oncology 2007, 25: 533-533. DOI: 10.1200/jco.2007.25.18_suppl.533.Peer-Reviewed Original ResearchHER2-positive breast cancerResidual cancer burdenHR-negative patientsAddition of trastuzumabHormone receptor statusPathologic complete responseNeoadjuvant chemotherapyBreast cancerPathologic responseReceptor statusResidual diseaseHER2-positive diseaseHR-positive patientsPathologic response rateSimilar pCR ratesHER2-positive patientsStandard neoadjuvant chemotherapyConcurrent trastuzumabRCB-IIRCB-IIIFAC chemotherapyPathologic reviewPCR rateComplete responseLymph nodes
2006
A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy
Symmans W, Peintinger F, Hatzis C, Kuerer H, Valero V, Hennessy B, Green M, Singletary E, Hortobagyi G, Pusztai L. A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy. Journal Of Clinical Oncology 2006, 24: 536-536. DOI: 10.1200/jco.2006.24.18_suppl.536.Peer-Reviewed Original ResearchDistant relapse-free survivalResidual cancer burdenPathologic complete responseResidual diseaseComplete responsePathologic responseAJCC stageCancer burdenMultivariate Cox regression analysisRCB-3AJCC stage IIIHigh-risk patientsCox regression analysisNeoadjuvant chemotherapy trialsRelapse-free survivalDifferent prognostic groupsMedian followNeoadjuvant trialsPaclitaxel scheduleWeekly paclitaxelChemotherapy trialsNeoadjuvant chemotherapyPCR rateStrength of associationSurvival benefit