2024
Datopotamab–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 subtypesPatientsTROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy
Bardia A, Pusztai L, Albain K, Ciruelos E, Im S, Hershman D, Kalinsky K, Isaacs C, Loirat D, Testa L, Tokunaga E, Wu J, Dry H, Barlow W, Kozarski R, Maxwell M, Harbeck N, Sharma P. TROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy. Therapeutic Advances In Medical Oncology 2024, 16: 17588359241248336. PMID: 38686016, PMCID: PMC11057345, DOI: 10.1177/17588359241248336.Peer-Reviewed Original ResearchInvasive disease-free survivalResidual invasive diseasePathological complete responseTriple-negative breast cancerDisease-free survivalNeoadjuvant therapyInvasive diseaseSurgical resectionBreast cancerHigh risk of disease recurrenceTopoisomerase I inhibitor payloadRisk of disease recurrenceStandard-of-care therapyAdjuvant treatment approachesPhase III studyTreatment of patientsWritten informed consentAntibody-drug conjugatesAged 18-yearsComplete responseNeoadjuvant treatmentInstitutional review boardOverall survivalDisease recurrenceIII studies
2022
Pembrolizumab vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer (TNBC): Phase 3 KEYNOTE-522 study
Kümmel S, Cortés J, Dent R, Pusztai L, McArthur H, Bergh J, Denkert C, Park Y, Hui R, Harbeck N, Takahashi M, Untch M, Fasching P, Cardoso F, Ding Y, Tryfonidis K, Aktan G, Karantza V, O’Shaughnessy J, Schmid P. Pembrolizumab vs placebo + chemotherapy as neoadjuvant treatment, followed by pembrolizumab vs placebo as adjuvant treatment for early triple-negative breast cancer (TNBC): Phase 3 KEYNOTE-522 study. European Journal Of Surgical Oncology 2022, 48: e30-e31. DOI: 10.1016/j.ejso.2021.12.430.Peer-Reviewed Original Research
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 significanceGanitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer
Yee D, Isaacs C, Wolf DM, Yau C, Haluska P, Giridhar KV, Forero-Torres A, Jo Chien A, Wallace AM, Pusztai L, Albain KS, Ellis ED, Beckwith H, Haley BB, Elias AD, Boughey JC, Kemmer K, Yung RL, Pohlmann PR, Tripathy D, Clark AS, Han HS, Nanda R, Khan QJ, Edmiston KK, Petricoin EF, Stringer-Reasor E, Falkson CI, Majure M, Mukhtar RA, Helsten TL, Moulder SL, Robinson PA, Wulfkuhle JD, Brown-Swigart L, Buxton M, Clennell JL, Paoloni M, Sanil A, Berry S, Asare SM, Wilson A, Hirst GL, Singhrao R, Asare AL, Matthews JB, Hylton NM, DeMichele A, Melisko M, Perlmutter J, Rugo HS, Fraser Symmans W, van‘t Veer L, Berry DA, Esserman LJ. Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer. Npj Breast Cancer 2021, 7: 131. PMID: 34611148, PMCID: PMC8492731, DOI: 10.1038/s41523-021-00337-2.Peer-Reviewed Original ResearchBreast cancerPredictive biomarkersPathologic complete response rateStage 2/3 breast cancerHER2-negative breast cancerPhase 2 clinical trialType I insulin-like growth factor receptorDrug-induced hyperglycemiaStandard neoadjuvant therapyComplete response rateUse of metforminI insulin-like growth factor receptorInsulin-like growth factor receptorPutative predictive biomarkersGrowth factor receptorI-SPY2Neoadjuvant therapyNeoadjuvant treatmentTreatment armsClinical trialsElevated hemoglobinNovel agentsGanitumabResponse rateCare paclitaxel
2020
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
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 therapy
2018
Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR
Generali D, Corona SP, Pusztai L, Rouzier R, Allevi G, Aguggini S, Milani M, Strina C, Frati A. Benefit of the addition of hormone therapy to neoadjuvant anthracycline-based chemotherapy for breast cancer: comparison of predicted and observed pCR. Journal Of Cancer Research And Clinical Oncology 2018, 144: 601-606. PMID: 29344722, DOI: 10.1007/s00432-017-2574-4.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnthracyclinesAntibiotics, AntineoplasticAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantCombined Modality TherapyFemaleHumansMiddle AgedNeoadjuvant TherapyPreoperative PeriodRetrospective StudiesTamoxifenTreatment OutcomeConceptsAnthracycline-based chemotherapyNeoadjuvant chemotherapyHormone receptor-positive breast cancer patientsHormone receptor positive BC patientsReceptor-positive breast cancer patientsHormone receptor-positive BCHormone receptor-positive patientsNeoadjuvant anthracycline-based chemotherapyPathological complete response ratePositive breast cancer patientsReceptor-positive patientsComplete response rateUse of chemotherapyLuminal B tumorsBreast cancer patientsPositive BC patientsCombination of tamoxifenCombination of chemotherapyAddition of tamoxifenSmall patient populationProbability of benefitCremona HospitalEndocrine therapyHormonal therapyNeoadjuvant treatment
2013
Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early Stage Breast Cancer and Evaluation of βIII‐Tubulin Expression as a Predictive Marker
Saura C, Tseng L, Chan S, Chacko RT, Campone M, Manikhas A, Nag SM, Leichman CG, Dasappa L, Fasching PA, de Mendoza F, Symmans WF, Liu D, Mukhopadhyay P, Horak C, Xing G, Pusztai L. Neoadjuvant Doxorubicin/Cyclophosphamide Followed by Ixabepilone or Paclitaxel in Early Stage Breast Cancer and Evaluation of βIII‐Tubulin Expression as a Predictive Marker. The Oncologist 2013, 18: 787-794. PMID: 23853246, PMCID: PMC3720631, DOI: 10.1634/theoncologist.2013-0075.Peer-Reviewed Original ResearchConceptsEarly-stage breast cancerStage breast cancerPathologic complete responseΒIII-tubulin expressionBreast cancerTreatment armsWeekly paclitaxelPositive patientsPredictive markerNeoadjuvant doxorubicin/cyclophosphamideRandomized phase II trialΒIII-tubulinCommon nonhematologic toxicitiesDoxorubicin/cyclophosphamideInvasive breast adenocarcinomaPhase II trialCore needle biopsyCycles of ACHigh response rateSignificant differencesNeoadjuvant cyclophosphamideNonhematologic toxicityNeoadjuvant treatmentII trialNegative patients
2012
Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial
Shen K, Qi Y, Song N, Tian C, Rice SD, Gabrin MJ, Brower SL, Symmans WF, O’Shaughnessy J, Holmes FA, Asmar L, Pusztai L. Cell Line Derived Multi-Gene Predictor of Pathologic Response to Neoadjuvant Chemotherapy in Breast Cancer: A Validation Study on US Oncology 02-103 Clinical Trial. BMC Medical Genomics 2012, 5: 51. PMID: 23158478, PMCID: PMC3536618, DOI: 10.1186/1755-8794-5-51.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsArea Under CurveBreast NeoplasmsCell Line, TumorClinical Trials as TopicDemographyFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGenes, NeoplasmHumansMiddle AgedMultivariate AnalysisNeoadjuvant TherapyReproducibility of ResultsTreatment OutcomeUnited StatesConceptsMulti-gene predictorsBreast cancerNeoadjuvant chemotherapyCombination chemotherapyCyclophosphamide combination chemotherapyDocetaxel/capecitabineEpirubicin/cyclophosphamideER-negative patientsPathologic complete responseER-positive cancersReceiver-operating characteristic curveAU-ROCCell linesBlinded validation studyNeoadjuvant treatmentMost patientsComplete responseER statusPathologic responseClinical outcomesValidation studyResidual diseaseTx groupClinical trialsEstrogen receptor
2011
Proposals for uniform collection of biospecimens from neoadjuvant breast cancer clinical trials: timing and specimen types
Loi S, Symmans WF, Bartlett J, Fumagalli D, Veer L, Forbes JF, Bedard P, Denkert C, Zujewski J, Viale G, Pusztai L, Esserman LJ, Leyland-Jones BR. Proposals for uniform collection of biospecimens from neoadjuvant breast cancer clinical trials: timing and specimen types. The Lancet Oncology 2011, 12: 1162-1168. PMID: 21684810, DOI: 10.1016/s1470-2045(11)70117-6.Peer-Reviewed Original ResearchConceptsNorth American Breast Cancer GroupBreast International GroupClinical trialsBiopsy procedureNeoadjuvant breast cancer trialsNeoadjuvant clinical trialsBreast cancer clinical trialsBreast cancer groupBreast cancer trialsStart of treatmentCancer clinical trialsNational Cancer InstituteNeoadjuvant trialsDefinitive surgeryNeoadjuvant treatmentCancer groupStudy protocolCancer trialsBreast cancerCancer InstituteUniform collectionTumor tissueBlood collectionTrialsSpecimen types
2008
Preoperative 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 cancer