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 subtypesPatients
2023
Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy
Licata L, Barreca M, Galbardi B, Dugo M, Viale G, Győrffy B, Karn T, Pusztai L, Gianni L, Callari M, Bianchini G. Breast cancers with high proliferation and low ER-related signalling have poor prognosis and unique molecular features with implications for therapy. British Journal Of Cancer 2023, 129: 2025-2033. PMID: 37935787, PMCID: PMC10703787, DOI: 10.1038/s41416-023-02477-7.Peer-Reviewed Original ResearchConceptsNeoadjuvant chemotherapyPoor prognosisBreast cancerTreatment responseHigher pathological complete response rateResponse rateHigh pathological response ratePathological complete response ratePathological response rateComplete response rateHigher proliferationHigh recurrence riskMolecular featuresEndocrine therapyLower ERHigh TMBDismal outcomePIK3CA mutationsMethodsGene expression dataClinical dataT cellsPotential therapyRecurrence riskTumorsUnique molecular featuresNeoadjuvant 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 advancesResponse to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer
Liedtke C, Mazouni C, Hess K, André F, Tordai A, Mejia J, Symmans W, Gonzalez-Angulo A, Hennessy B, Green M, Cristofanilli M, Hortobagyi G, Pusztai L. Response to Neoadjuvant Therapy and Long-Term Survival in Patients With Triple-Negative Breast Cancer. Journal Of Clinical Oncology 2023, 41: 1809-1815. PMID: 36989609, DOI: 10.1200/jco.22.02572.Peer-Reviewed Original ResearchTriple-negative breast cancerPathologic complete response rateNeoadjuvant chemotherapyResidual diseaseBreast cancerProgesterone receptorEstrogen receptorHuman epidermal growth factor receptor 2 (HER2) expressionSurvival rateEpidermal growth factor receptor 2 expressionProgression-free survival ratesM.D. Anderson Cancer CenterComplete response rateOverall survival rateAnderson Cancer CenterReceptor 2 expressionLong-term survivalBone recurrenceNeoadjuvant therapyPostrecurrence survivalVisceral metastasesWorse OSWorse survivalRelapse rateCancer Center
2022
Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm DL, Pusztai L. Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. Clinical Cancer Research 2022, 28: 3720-3728. PMID: 35903931, PMCID: PMC9444984, DOI: 10.1158/1078-0432.ccr-22-0862.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsTriple-negative breast cancerNon-AA patientsEvent-free survivalPhase I/II clinical trialsClinical trialsNeoadjuvant chemotherapyOverall survivalAA patientsEarly-stage triple-negative breast cancerIncidence of irAEsPathologic complete response rateSignificant associationMultivariate logistic regression analysisTumor-infiltrating lymphocyte countsComplete response ratePrimary efficacy endpointPD-L1 statusProportional hazards modelLogistic regression analysisAfrican American womenEFS ratesNeoadjuvant immunotherapyEfficacy endpointAdverse eventsClinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm D, Pusztai L. Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.16_suppl.516.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerMultivariate logistic regression analysisPD-L1 statusLogistic regression analysisAA raceOverall survivalPathologic responseClinical trialsBreast cancerEarly-stage triple-negative breast cancerIncidence of irAEsPhase I/II trialPathologic complete response rateSignificant associationPhase I/II clinical trialsBaseline body mass indexSafety of immunotherapyWeekly nab-paclitaxelCharlson Comorbidity IndexComplete response ratePrimary efficacy endpointPD-L1 expressionBody mass indexBreast cancer recurrencePathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial.
Huppert L, Rugo H, Pusztai L, Mukhtar R, Chien A, Yau C, Wolf D, Berry D, van 't Veer L, Yee D, DeMichele A, Esserman L, Consortium I. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. Journal Of Clinical Oncology 2022, 40: 504-504. DOI: 10.1200/jco.2022.40.16_suppl.504.Peer-Reviewed Original ResearchI-SPY2 trialInvestigational agentsMolecular subtypesNodal statusPathologic complete response rateMultiple investigational agentsComplete response ratePhase 3 trialHER2- breast cancerLuminal statusNeoadjuvant therapyPrimary endpointImmune signaturesPCR rateTreatment armsHeterogenous diseaseBC therapySubtype 5Breast cancerImmune biologyResponse ratePembrolizumabHormone receptorsDiseaseTrialsRedefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies
Wolf DM, Yau C, Wulfkuhle J, Brown-Swigart L, Gallagher RI, Lee PRE, Zhu Z, Magbanua MJ, Sayaman R, O’Grady N, Basu A, Delson A, Coppé JP, Lu R, Braun J, Investigators I, Asare SM, Sit L, Matthews JB, Perlmutter J, Hylton N, Liu MC, Pohlmann P, Symmans WF, Rugo HS, Isaacs C, DeMichele AM, Yee D, Berry DA, Pusztai L, Petricoin EF, Hirst GL, Esserman LJ, van 't Veer LJ. Redefining breast cancer subtypes to guide treatment prioritization and maximize response: Predictive biomarkers across 10 cancer therapies. Cancer Cell 2022, 40: 609-623.e6. PMID: 35623341, PMCID: PMC9426306, DOI: 10.1016/j.ccell.2022.05.005.Peer-Reviewed Original ResearchConceptsBreast cancer subtypesHormone receptorsHuman epidermal growth factor receptor 2 (HER2) statusCancer subtypesEpidermal growth factor receptor 2 statusPathologic complete response rateTreatment prioritizationComplete response ratePatient selectionPredictive biomarkersTreatment allocationPlatform trialsClinical dataLuminal phenotypeTreatment selectionResponse rateTumor biologyNew treatmentsDrug responseSubtypesCancer therapyBiomarkersProtein/phosphoproteinGene expressionDiverse biologyTreatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials
Marczyk M, Mrukwa A, Yau C, Wolf D, Chen Y, Balassanian R, Nanda R, Parker B, Krings G, Sattar H, Zeck J, Albain K, Boughey J, Liu M, Elias A, Clark A, Venters S, Shad S, Basu A, Asare S, Buxton M, Asare A, Rugo H, Perlmutter J, DeMichele A, Yee D, Berry D, Veer L, Symmans W, Esserman L, Pusztai L, Consortium I. Treatment Efficacy Score—continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials. Annals Of Oncology 2022, 33: 814-823. PMID: 35513244, DOI: 10.1016/j.annonc.2022.04.072.Peer-Reviewed Original ResearchConceptsTrial armsExperimental armSurvival differencesExact testPathologic complete response rateClinical trial armsI-SPY2 trialNeoadjuvant chemotherapy efficacyComplete response rateBreast cancer trialsCytotoxic efficacyFisher's exact testImpact of treatmentNeoadjuvant chemotherapyPCR ratePathologic responseResidual cancerControl cohortCancer trialsAssessed associationsChemotherapy efficacyEarly surrogateOlaparib armResponse rateHigher cytotoxic efficacy
2021
Ganitumab 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 paclitaxelTumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer
Gonzalez-Ericsson PI, Wulfkhule JD, Gallagher RI, Sun X, Axelrod ML, Sheng Q, Luo N, Gomez H, Sanchez V, Sanders M, Pusztai L, Petricoin E, Blenman K, Balko JM, Team I, Leyland-Jones B, Agency C, Chia S, Serpanchy R, Yu C, University E, McMillan S, Mosley R, Nguyen K, Wood E, Zelnak A, University G, Dillis C, Donnelly R, Harrington T, Isaacs C, Kallakury B, Liu M, Lynce F, Oppong B, Pohlmann P, Tousimis E, Warren R, Willey S, Wong J, Zeck J, Center L, Albain K, Bartolotta M, Bova D, Brooks C, Busby B, Czaplicki K, Duan X, Gamez R, Ganesh K, Gaynor E, Godellas C, Grace-Louthen C, Kuritza T, Lo S, Nagamine A, Perez C, Robinson P, Rosi D, Vaince F, Ward K, Hospital I, Choquette K, Edmiston K, Gallimore H, McGovern J, Mokarem K, Pajaniappan M, Rassulova S, Scott K, Sherwood K, Wright J, Clinic A, Anderson K, Gray R, Myers S, Northfelt D, Pockaj B, Roedig J, Wasif N, Clinic R, Arens A, Boughey J, Brandt K, Carroll J, Chen B, Connors A, Degnim A, Farley D, Greenlee S, Haddad T, Hieken T, Hobday T, Jakub J, Liberte L, Liu M, Loprinzi C, Menard L, Moe M, Moynihan T, O'Sullivan C, Olson E, Peethambaram P, Ruddy K, Russell B, Rynearson A, Smith D, Visscher D, Windish A, Institute H, Cox K, Dawson K, Newton O, Ramirez W, University O, Bengtson H, Bucher J, Chui S, Gilbert-Ghormley B, Hampton R, Kemmer K, Kurdyla D, Nauman D, Spear J, Wilson A, Institute S, Beatty D, Dawson P, Ellis E, Fer M, Hanson J, Goetz M, Haddad T, Iriarte D, Kaplan H, Porter B, Rinn K, Thomas H, Thornton S, Tickman R, Varghis N, Birmingham U, Caterinichia V, Santos J, Falkson C, Forero A, Krontiras H, Vaklavas C, Wei S, University of Arizona, Bauland A, Inclan L, Lewallen D, Powell A, Roney C, Schmidt K, Viscusi R, Wright H, University of California S, Blair S, Boles S, Bykowski J, Datnow B, Densley L, Eghtedari M, Genna V, Hasteh F, Helsten T, Kormanik P, Ojeda-Fournier H, Onyeacholem I, Parker B, Podsada K, Schwab R, Wallace A, Yashar C, University of California S, Alvarado M, Au A, Balassanian R, Benz C, Buxton M, Chen Y, Chien J, D'Andrea C, Davis S, Esserman L, Ewing C, Goga A, Hirst G, Hwang M, Hylton N, Joe B, Lyandres J, Kadafour M, Krings G, Melisko M, Moasser M, Munter P, Ngo Z, Park J, Price E, Rugo H, Veer L, Wong J, Yau C, University of Chicago, Abe H, Jaskowiak N, Nanda R, Olopade F, Schacht D, University of Colorado D, Borges V, Colvin T, Diamond J, Elias A, Finlayson C, Fisher C, Hardesty L, Kabos P, Kounalakis N, Mayordomo J, McSpadden T, Murphy C, Rabinovitch R, Sams S, Shagisultanova E, University of Kansas, Baccaray S, Khan Q, University of Minnesota, Beckwith H, Blaes A, Emory T, Haddad T, Hui J, Klein M, Kuehn-Hajder J, Nelson M, Potter D, Tuttle T, Yee D, Zera R, University of Pennsylvania, Bayne L, Bradbury A, Clark A, DeMichele A, Domchek S, Fisher C, Fox K, Frazee D, Lackaye M, Matro J, McDonald E, Rosen M, Shah P, Tchou J, Volpe M, Center U, Alvarez R, Barcenas C, Berry D, Booser D, Brewster A, Brown P, Gonzalez-Angulo A, Ibrahim N, Karuturi M, Koenig K, Moulder S, Murray J, Murthy R, Pusztai L, Saigal B, Symmans W, Tripathy D, Theriault R, Ueno N, Valero V, California U, Brown M, Carranza M, Flores Y, Lang J, Luna A, Perez N, Tripathy D, Watkins K, Center U, Armstrong S, Boyd C, Chen L, Clark V, Frankel A, Euhus D, Froehlich T, Goudreau S, Haley B, Harker-Murray A, Klemow D, Leitch A, Leon R, Li H, Morgan T, Qureshi N, Rao R, Reeves M, Rivers A, Sadeghi N, Seiler S, Staves B, Tagoe V, Thomas G, Tripathy D, Unni N, Weyandt S, Wooldridge R, Zuckerman J, Universty of Washington, Korde L, Griffin M, Butler B, Cundy A, Rubinstein L, Hixson C. Tumor-Specific Major Histocompatibility-II Expression Predicts Benefit to Anti–PD-1/L1 Therapy in Patients With HER2-Negative Primary Breast CancerMHC-II Is an Immunotherapy Biomarker in Early Breast Cancer. Clinical Cancer Research 2021, 27: 5299-5306. PMID: 34315723, PMCID: PMC8792110, DOI: 10.1158/1078-0432.ccr-21-0607.Peer-Reviewed Original ResearchConceptsStandard neoadjuvant chemotherapyTriple-negative breast cancerNeoadjuvant chemotherapyBreast cancerMHC-IITumor cellsAnti-PD-1/L1 therapyEstrogen receptor-positive breast cancerPhase II/III clinical trialsNeoadjuvant breast cancer settingPathologic complete response rateHER2-negative breast cancerReceptor-positive breast cancerAddition of immunotherapyHLA-DR positivityBreast cancer settingComplete response rateHER2-negative patientsCohort of patientsEarly breast cancerMHC-II expressionPan-cancer biomarkerImmunotherapy benefitL1 therapyMost patientsDurvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial
Pusztai L, Yau C, Wolf DM, Han HS, Du L, Wallace AM, String-Reasor E, Boughey JC, Chien AJ, Elias AD, Beckwith H, Nanda R, Albain KS, Clark AS, Kemmer K, Kalinsky K, Isaacs C, Thomas A, Shatsky R, Helsten TL, Forero-Torres A, Liu MC, Brown-Swigart L, Petricoin EF, Wulfkuhle JD, Asare SM, Wilson A, Singhrao R, Sit L, Hirst GL, Berry S, Sanil A, Asare AL, Matthews JB, Perlmutter J, Melisko M, Rugo HS, Schwab RB, Symmans WF, Yee D, Van't Veer LJ, Hylton NM, DeMichele AM, Berry DA, Esserman LJ. Durvalumab with olaparib and paclitaxel for high-risk HER2-negative stage II/III breast cancer: Results from the adaptively randomized I-SPY2 trial. Cancer Cell 2021, 39: 989-998.e5. PMID: 34143979, PMCID: PMC11064785, DOI: 10.1016/j.ccell.2021.05.009.Peer-Reviewed Original ResearchConceptsHER2-negative breast cancerTriple-negative breast cancerI-SPY2 trialBreast cancerNeoadjuvant chemotherapyStage II/III HER2-negative breast cancerStage II/III breast cancerGrade 3 adverse eventsPathologic complete response ratePD-L1 inhibitor durvalumabMast cell signaturePaclitaxel neoadjuvant chemotherapyComplete response rateHER2-negative patientsStandard neoadjuvant chemotherapyHER2-negative cancersPARP inhibitor olaparibAdverse eventsGene expression signaturesCare controlSuperior efficacyImmune responseResponse rateCancerInhibitor olaparib
2018
Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Burrello T, Abu-Khalaf M, Sabbath K, Sanft T, Brandt DS, Hofstatter EW, Hatzis C, DiGiovanna MP, Pusztai L. Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I–III HER2-positive breast cancer. Breast Cancer Research And Treatment 2018, 169: 333-340. PMID: 29396664, DOI: 10.1007/s10549-017-4653-2.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerPhase II trialII trialNeoadjuvant chemotherapyPCR rateHormone receptorsBreast cancerGrade 3/4 adverse eventsPathologic complete response rateCyclophosphamide neoadjuvant chemotherapyComplete response rateSymptomatic heart failureAsymptomatic decreaseNeoadjuvant settingWeekly paclitaxelAdverse eventsHeart failureTherapeutic plateauCardiac functionInterim analysisStage IResponse ratePurposeThe purposePatientsNegative casesBenefit 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
2017
Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer
Fujii T, Kogawa T, Dong W, Sahin AA, Moulder S, Litton JK, Tripathy D, Iwamoto T, Hunt KK, Pusztai L, Lim B, Shen Y, Ueno NT. Revisiting the definition of estrogen receptor positivity in HER2-negative primary breast cancer. Annals Of Oncology 2017, 28: 2420-2428. PMID: 28961844, PMCID: PMC5834134, DOI: 10.1093/annonc/mdx397.Peer-Reviewed Original ResearchConceptsHER2-negative primary breast cancerAdjuvant hormonal therapyPrimary breast cancerTriple-negative breast cancerEstrogen receptor positivityHormonal therapyBreast cancerER expressionNeoadjuvant chemotherapyOverall survivalReceptor positivityPathological complete response rateHER2-negative breast cancerStage IIHuman epidermal growth factor 2Better long-term outcomesEpidermal growth factor 2Complete response rateProgesterone receptor expressionLong-term outcomesNegative breast cancerTerms of pCRLogistic regression modelsDefinitive surgeryGrowth factor 2Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial.
Pusztai L, Silber A, Hofstatter E, Chung G, Horowitz N, Lannin D, Killelea B, Chagpar A, Szekely B, Frederick C, Rispoli L, DiGiovanna M. Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial. Journal Of Clinical Oncology 2017, 35: 572-572. DOI: 10.1200/jco.2017.35.15_suppl.572.Peer-Reviewed Original ResearchImmune related adverse eventsTriple-negative breast cancerWeekly nab-paclitaxelWeeks of therapyNeoadjuvant chemotherapyDose levelsNab-paclitaxelPhase I/II trialPathologic complete response rateChest X-ray abnormalitiesDoxorubicin/cyclophosphamidePhase I toxicityComplete response rateImmune checkpoint inhibitorsPhase I portionRelated adverse eventsPhase II portionPhase I partX-ray abnormalitiesNegative breast cancerSequential taxaneAnthracycline chemotherapyCheckpoint inhibitorsII trialAdverse eventsPathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer.
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Abu-Khalaf M, Sabbath K, Sanft T, Fischbach N, Brandt D, Hofstatter E, DiGiovanna M, Pusztai L. Pathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer. Journal Of Clinical Oncology 2017, 35: 577-577. DOI: 10.1200/jco.2017.35.15_suppl.577.Peer-Reviewed Original ResearchPathologic complete response rateHER2-positive breast cancerDual HER2 blockadeComplete response ratePCR rateEstrogen receptorHER2 blockadeBreast cancerStage IResponse rateGrade 3/4 adverse eventsSymptomatic congestive heart failureClinical stage ICompletion of chemotherapyPhase II studyTaxane-based chemotherapyCongestive heart failureEfficacy of anthracyclinesPositive breast cancerNormal cardiac functionEntire treatment durationER- cancersER cohortNeoadjuvant pertuzumabWeekly paclitaxelDifferences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races.
Szekely B, Safonov A, Karn T, Bhagwagar S, Killelea B, Silber A, Hatzis C, Pusztai L. Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races. Journal Of Clinical Oncology 2017, 35: e13028-e13028. DOI: 10.1200/jco.2017.35.15_suppl.e13028.Peer-Reviewed Original ResearchTriple-negative breast cancerNon-AA patientsImmune microenvironmentAfrican American womenImmune signaturesNeoantigen loadImmune metagenesLower pathologic complete response (pCR) ratesPathologic complete response rateComplete response rateNegative breast cancerAmerican womenMann-Whitney U testSignificant differencesClonal heterogeneityTCGA data setsDeletion loadNeoadjuvant therapyLymphocyte countTIL countAA patientsOverall mutational loadHistologic tumorsBreast cancerTreatment responseEffects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial.
Pelekanou V, Barlow W, von Wahlde M, Wasserman B, Lo Y, Hayes D, Hortobagyi G, Gralow J, Tripathy D, Livingston R, Porter P, Nahleh Z, Rimm D, Pusztai L. Effects of neoadjuvant chemotherapy (NAC) on tumor infiltrating lymphocytes (TIL) and PD-L1 expression in the SWOG S0800 clinical trial. Journal Of Clinical Oncology 2017, 35: 519-519. DOI: 10.1200/jco.2017.35.15_suppl.519.Peer-Reviewed Original ResearchPD-L1 expressionNeoadjuvant chemotherapyNAC armTIL countClinical trialsImmune parametersNAC samplesBaseline PD-L1 expressionPathologic complete response rateDose-dense doxorubicinComplete response ratePD-L1 immunohistochemistryHER2-negative casesMinority of casesNab-paclitaxelResidual diseaseMean changeResponse rateLogistic regressionTILsBaselineEpithelial cellsHigh PCRChemotherapyTumorsRNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial
Fumagalli D, Venet D, Ignatiadis M, Azim HA, Maetens M, Rothé F, Salgado R, Bradbury I, Pusztai L, Harbeck N, Gomez H, Chang TW, Coccia-Portugal MA, Di Cosimo S, de Azambuja E, de la Peña L, Nuciforo P, Brase JC, Huober J, Baselga J, Piccart M, Loi S, Sotiriou C. RNA Sequencing to Predict Response to Neoadjuvant Anti-HER2 Therapy: A Secondary Analysis of the NeoALTTO Randomized Clinical Trial. JAMA Oncology 2017, 3: 227-234. PMID: 27684533, PMCID: PMC5374044, DOI: 10.1001/jamaoncol.2016.3824.Peer-Reviewed Original ResearchEvent-free survivalAnti-HER2 therapyAnti-HER2 agentsErbB2/HER2Genomic grade indexCombination armTreatment armsGene signatureBreast cancerHER2-positive early-stage breast cancerNeoadjuvant anti-HER2 therapyPathologic complete response rateHuman epidermal growth factor receptor 2Early-stage breast cancerEpidermal growth factor receptor 2Candidate predictive markersCycles of fluorouracilDual HER2 blockadeImmune gene signaturesComplete response rateGrowth factor receptor 2Positive breast cancerLong-term outcomesRandomized clinical trialsHigh PCR