2024
Multi-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 cellsPathologic 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-upThe 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 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 subtypesPatientsPeripheral 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 responseNeoadjuvant 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-30PlaceboEvent-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 responseTROPION-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
2023
Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Rediti M, Fernandez-Martinez A, Venet D, Rothé F, Hoadley K, Parker J, Singh B, Campbell J, Ballman K, Hillman D, Winer E, El-Abed S, Piccart M, Di Cosimo S, Symmans W, Krop I, Salgado R, Loi S, Pusztai L, Perou C, Carey L, Sotiriou C. Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials. Nature Communications 2023, 14: 7053. PMID: 37923752, PMCID: PMC10624889, DOI: 10.1038/s41467-023-42635-2.Peer-Reviewed Original ResearchConceptsEvent-free survivalHER2-positive breast cancerPathological complete responseCALGB 40601Breast cancerBreast pathological complete responseStromal tumor-infiltrating lymphocytesHormone receptor statusPhase III trialsClinical nodal statusIndependent prognostic factorTumor-infiltrating lymphocytesIdentification of patientsBreast cancer prognosisT cell receptorNeoadjuvant paclitaxelNeoadjuvant therapyIII trialsNodal statusComplete responsePrognostic factorsPrognostic scoreReceptor statusClinicopathological featuresResidual diseasePembrolizumab 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 armsMammaPrint Index as a predictive biomarker for neoadjuvant chemotherapy response and outcome in patients with HR+HER2- breast cancer in NBRST.
Beitsch P, Pellicane J, Pusztai L, Baron P, Cobain E, Murray M, Ashikari A, Kelemen P, Mislowsky A, Barone J, Cowan K, Layeequr Rahman R, Dooley W, Menicucci A, Finn C, Audeh M, Whitworth P. MammaPrint Index as a predictive biomarker for neoadjuvant chemotherapy response and outcome in patients with HR+HER2- breast cancer in NBRST. Journal Of Clinical Oncology 2023, 41: 521-521. DOI: 10.1200/jco.2023.41.16_suppl.521.Peer-Reviewed Original ResearchDistant metastasis-free survivalPathological complete responseNeoadjuvant chemotherapyHigh riskGrade 3 tumorsLymph node statusObservational prospective studyHigh-risk tumorsKaplan-Meier analysisStage breast cancerLog-rank testPrediction of chemosensitivityESBC patientsMammaPrint testSYMPHONY trialsFree survivalNeoadjuvant therapyClinicopathologic subtypesComplete responseDistant metastasisImmune therapyMeier analysisRisk tumorsNode statusProspective studyImage 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 correlationEvent-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer
Schmid P, Cortes J, Dent R, Pusztai L, McArthur H, Kümmel S, Bergh J, Denkert C, Park YH, Hui R, Harbeck N, Takahashi M, Untch M, Fasching PA, Cardoso F, Andersen J, Patt D, Danso M, Ferreira M, Mouret-Reynier MA, Im SA, Ahn JH, Gion M, Baron-Hay S, Boileau JF, Ding Y, Tryfonidis K, Aktan G, Karantza V, O'Shaughnessy J. Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. New England Journal Of Medicine 2022, 386: 556-567. PMID: 35139274, DOI: 10.1056/nejmoa2112651.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsChemotherapy, AdjuvantFemaleHumansIntention to Treat AnalysisKaplan-Meier EstimateMiddle AgedNeoadjuvant TherapyProgression-Free SurvivalTriple Negative Breast NeoplasmsConceptsEarly triple-negative breast cancerTriple-negative breast cancerEvent-free survivalCycles of pembrolizumabPathological complete responseDefinitive surgeryBreast cancerNeoadjuvant chemotherapyComplete responseLonger event-free survivalUntreated stage IIPrimary end pointPhase 3 trialSecond primary cancerDoxorubicin-cyclophosphamideNeoadjuvant pembrolizumabNeoadjuvant phaseAdjuvant therapyDistant recurrenceNeoadjuvant therapyAdverse eventsPrimary cancerSafety profileDisease progressionPembrolizumab
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 association