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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHormonesHumansNeoadjuvant TherapyRandomized Controlled Trials as TopicReceptor, ErbB-2TrastuzumabTreatment OutcomeTumor MicroenvironmentConceptsEvent-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 diseaseASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest
Kim L, Coman M, Pusztai L, Park T. ASO Visual Abstract: Neoadjuvant Immunotherapy in Early Triple-Negative Breast Cancers—Catching up with the Rest. Annals Of Surgical Oncology 2023, 30: 6452-6453. DOI: 10.1245/s10434-023-13842-4.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleHumansImmunotherapyNeoadjuvant TherapyTriple Negative Breast NeoplasmsThymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226)
Bergqvist M, Nordmark A, Williams A, Paoletti C, Barlow W, Cobain E, Mehta R, Gralow J, Hortobagyi G, Albain K, Pusztai L, Sharma P, Godwin A, Thompson A, Hayes D, Rae J. Thymidine kinase activity levels in serum can identify HR+ metastatic breast cancer patients with a low risk of early progression (SWOG S0226). Biomarkers 2023, 28: 313-322. PMID: 36647745, PMCID: PMC10681159, DOI: 10.1080/1354750x.2023.2168063.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkersBreast NeoplasmsFemaleHumansPrognosisProgression-Free SurvivalReceptor, ErbB-2Thymidine KinaseConceptsMetastatic breast cancerNegative predictive valueEndocrine therapyThymidine kinase activityLower riskSingle-agent endocrine therapyMetastatic breast cancer patientsLonger progression-free survivalHigh negative predictive valueProgression-free survivalBreast cancer patientsSerum thymidine kinase activityAdditional therapyOverall survivalSuch patientsCancer patientsBlood drawEarly progressionDisease progressionRapid progressionBreast cancerPatientsSubsequent timepointsPredictive valuePotential biomarkersCisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial
Rodler E, Sharma P, Barlow W, Gralow J, Puhalla S, Anders C, Goldstein L, Tripathy D, Brown-Glaberman U, Huynh T, Szyarto C, Godwin A, Pathak H, Swisher E, Radke M, Timms K, Lew D, Miao J, Pusztai L, Hayes D, Hortobagyi G. Cisplatin with veliparib or placebo in metastatic triple-negative breast cancer and BRCA mutation-associated breast cancer (S1416): a randomised, double-blind, placebo-controlled, phase 2 trial. The Lancet Oncology 2023, 24: 162-174. PMID: 36623515, PMCID: PMC9924094, DOI: 10.1016/s1470-2045(22)00739-2.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsCisplatinDouble-Blind MethodFemaleHumansMutationNeoplasm Recurrence, LocalPoly(ADP-ribose) Polymerase InhibitorsQuality of LifeTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerMedian progression-free survivalProgression-free survivalMetastatic breast cancerMetastatic triple-negative breast cancerGermline BRCA1/2Phase 2 trialVeliparib groupPlacebo groupPlatinum-based chemotherapyBreast cancerHomologous recombination deficiencyAdverse eventsPARP inhibitorsEligible patientsMetastatic diseaseEastern Cooperative Oncology Group performance statusBRCA mutation-associated breast cancerInvestigator-assessed progression-free survivalTreatment-related adverse eventsRecurrent triple-negative breast cancerAcademic clinical sitesAddition of veliparibCommon grade 3Lines of chemotherapy
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 ResearchMeSH KeywordsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkersBreast NeoplasmsFemaleHumansNeoadjuvant TherapyTriple Negative Breast NeoplasmsConceptsImmune-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 eventsRedefining 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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsFemaleHumansNeoadjuvant TherapyReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneConceptsBreast 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 ResearchMeSH KeywordsAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansNeoadjuvant TherapyNeoplasm, ResidualTreatment OutcomeConceptsTrial 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 efficacyPredictive 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 ResearchMeSH KeywordsAlbuminsAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsCyclophosphamideDoxorubicinFemaleHumansNeoadjuvant TherapyPaclitaxelTransforming Growth Factor betaTriple Negative Breast NeoplasmsConceptsBasal-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 cycleEvent-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
21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer
Kalinsky K, Barlow WE, Gralow JR, Meric-Bernstam F, Albain KS, Hayes DF, Lin NU, Perez EA, Goldstein LJ, Chia SKL, Dhesy-Thind S, Rastogi P, Alba E, Delaloge S, Martin M, Kelly CM, Ruiz-Borrego M, Gil-Gil M, Arce-Salinas CH, Brain EGC, Lee ES, Pierga JY, Bermejo B, Ramos-Vazquez M, Jung KH, Ferrero JM, Schott AF, Shak S, Sharma P, Lew DL, Miao J, Tripathy D, Pusztai L, Hortobagyi GN. 21-Gene Assay to Inform Chemotherapy Benefit in Node-Positive Breast Cancer. New England Journal Of Medicine 2021, 385: 2336-2347. PMID: 34914339, PMCID: PMC9096864, DOI: 10.1056/nejmoa2108873.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleGene Expression ProfilingHumansLymphatic MetastasisMiddle AgedNeoplasm Recurrence, LocalPostmenopausePremenopauseProspective StudiesReceptor, ErbB-2Receptors, SteroidReverse Transcriptase Polymerase Chain ReactionConceptsInvasive disease-free survivalDistant relapse-free survivalDisease-free survivalRelapse-free survivalChemotherapy benefitRecurrence scoreBreast cancerChemoendocrine therapyAdjuvant chemotherapyPostmenopausal womenPremenopausal womenLymph nodesAxillary lymph node-negative breast cancerLymph node-negative breast cancerPositive axillary lymph nodesHER2-negative breast cancerNode-positive breast cancerHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Positive lymph node diseasePositive lymph nodesSecondary end pointsAxillary lymph nodesLymph node diseaseGrowth factor receptor 2A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222
Moore HCF, Barlow WE, Somlo G, Gralow JR, Schott AF, Hayes DF, Kuhn P, Hicks JB, Welter L, Dy PA, Yeon CH, Conlin AK, Balcueva E, Lew DL, Tripathy D, Pusztai L, Hortobagyi GN. A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor–positive Breast Cancer, SWOG S1222SWOG S1222. Clinical Cancer Research 2021, 28: 611-617. PMID: 34844978, PMCID: PMC9782801, DOI: 10.1158/1078-0432.ccr-21-3131.Peer-Reviewed Original ResearchMeSH KeywordsAnastrozoleAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsEverolimusFemaleFulvestrantHumansReceptor, ErbB-2Receptors, EstrogenConceptsProgression-free survivalHER2-negative breast cancerFirst-line treatmentBreast cancerAdvanced hormone receptor-positive breast cancerAdvanced hormone-sensitive breast cancerHER2-negative advanced breast cancerHormone receptor-positive breast cancerHormone-sensitive breast cancerRandomized placebo-controlled trialReceptor-positive breast cancerCombination endocrine therapyMetastatic hormone receptorPlacebo-controlled trialAdvanced breast cancerMainstay of treatmentFront-line treatmentBaseline CTCsEndocrine therapyEndocrine treatmentPostmenopausal womenMetastatic diseaseOverall survivalPrognostic impactSystemic therapyAssessment 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 ResearchMeSH KeywordsAdultAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualPrognosisProgression-Free SurvivalReceptor, ErbB-2ConceptsEvent-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 significanceComparison of Autologous Breast Reconstruction Complications by Type of Neoadjuvant Chemotherapy Regimen
Olawoyin OM, Mehta S, Chouairi F, Gabrick KS, Avraham T, Pusztai L, Alperovich M. Comparison of Autologous Breast Reconstruction Complications by Type of Neoadjuvant Chemotherapy Regimen. Plastic & Reconstructive Surgery 2021, 148: 1186-1196. PMID: 34644277, DOI: 10.1097/prs.0000000000008505.Peer-Reviewed Original ResearchMeSH KeywordsAdultAnthracyclinesAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsBridged-Ring CompoundsChemotherapy, AdjuvantFemaleHumansMammaplastyMastectomyMiddle AgedNeoadjuvant TherapyPostoperative ComplicationsSurgical FlapsTaxoidsTreatment OutcomeConceptsNeoadjuvant chemotherapy regimensMicrovascular breast reconstructionNeoadjuvant chemotherapyChemotherapy regimensComplication rateFat necrosisBreast reconstructionImmune cellsCLINICAL QUESTION/LEVELMultivariate binary logistic regressionYale-New Haven HospitalAdministration of taxanesBreast Reconstruction ComplicationsInclusion of anthracyclinesNeoadjuvant chemotherapy regimenDosage of chemotherapyNew Haven HospitalNeoadjuvant chemotherapy completionLogistic regression modelsBinary logistic regressionOncologic historyTaxane administrationChemotherapy regimenChemotherapy completionPathologic responseEvaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial
Paoletti C, Barlow WE, Cobain EF, Bergqvist M, Mehta RS, Gralow JR, Hortobagyi GN, Albain KS, Pusztai L, Sharma P, Godwin AK, Thompson AM, Hayes DF, Rae JM. Evaluating Serum Thymidine Kinase 1 in Hormone Receptor Positive Metastatic Breast Cancer Patients Receiving First Line Endocrine Therapy in the SWOG S0226 Trial. Clinical Cancer Research 2021, 27: clincanres.1562.2021. PMID: 34521624, PMCID: PMC8595696, DOI: 10.1158/1078-0432.ccr-21-1562.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicFemaleHumansKaplan-Meier EstimateMiddle AgedPrognosisReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneRetrospective StudiesThymidine KinaseTreatment OutcomeConceptsProgression-free survivalMetastatic breast cancerFirst-line endocrine therapyOverall survivalEndocrine therapyHormone receptor-positive metastatic breast cancer patientsHormone receptor-positive metastatic breast cancerPositive metastatic breast cancer patientsSubsequent progression-free survivalMetastatic breast cancer patientsWorse progression-free survivalCombination endocrine therapySerum thymidine kinase 1Trial of anastrozoleThymidine kinase 1 activityBreast cancer patientsLog-rank testLine endocrine therapyDu/LAdjuvant tamoxifenPrognostic effectCox regressionPoor prognosisWorse prognosisKaplan-MeierAlpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer
Vathiotis IA, Moutafi MK, Divakar P, Aung TN, Qing T, Fernandez A, Yaghoobi V, El-Abed S, Wang Y, Guillaume S, Nuciforo P, Huober J, Di Cosimo S, Kim SB, Harbeck N, Gomez H, Shafi S, Syrigos KN, Fountzilas G, Sotiriou C, Pusztai L, Warren S, Rimm DL. Alpha-smooth muscle actin expression in the stroma predicts resistance to trastuzumab in patients with early-stage HER2-positive breast cancer. Clinical Cancer Research 2021, 27: 6156-6163. PMID: 34465600, PMCID: PMC8595766, DOI: 10.1158/1078-0432.ccr-21-2103.Peer-Reviewed Original ResearchMeSH KeywordsActinsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease-Free SurvivalFemaleHumansMuscle, SmoothNeoadjuvant TherapyReceptor, ErbB-2TrastuzumabTreatment OutcomeConceptsDisease-free survivalHER2-positive breast cancerShorter disease-free survivalBreast cancerQuantitative immunofluorescenceEarly-stage HER2-positive breast cancerAlpha-smooth muscle actin expressionAlpha-smooth muscle actinProgesterone receptor statusHigh α-SMA expressionDigital Spatial ProfilerΑ-SMA expressionPromising candidate biomarkerCompanion diagnostic testsMuscle actin expressionDigital spatial profilingCohort validationNeoadjuvant lapatinibAdjuvant trastuzumabReceptor statusClinical trialsUnivariate analysisEstrogen receptorMAIN OUTCOMEΑ-SMACopy 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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsDNA Copy Number VariationsFemaleHumansNeoadjuvant TherapyNeoplasm Recurrence, LocalReceptor, ErbB-2TrastuzumabConceptsPathologic 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 associationTumor-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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHistocompatibilityHumansNeoadjuvant TherapyReceptor, ErbB-2Retrospective StudiesTriple Negative Breast NeoplasmsConceptsStandard 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 ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleFollow-Up StudiesHumansMiddle AgedNeoadjuvant TherapyPaclitaxelPhthalazinesPiperazinesPrognosisReceptor, ErbB-2Survival RateYoung AdultConceptsHER2-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 olaparibPredicted 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 ResearchMeSH KeywordsAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsFemaleHormonesHumansNeoadjuvant TherapyNeoplasm Recurrence, LocalPrognosisReceptor, ErbB-2Receptors, ProgesteroneConceptsResidual 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
PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer
Ahmed FS, Gaule P, McGuire J, Patel K, Blenman K, Pusztai L, Rimm DL. PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. Clinical Cancer Research 2020, 26: 5456-5461. PMID: 32709714, PMCID: PMC7572612, DOI: 10.1158/1078-0432.ccr-20-1303.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, MonoclonalAntigens, CDAntigens, Differentiation, MyelomonocyticAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBiomarkers, TumorCell ProliferationFemaleGene Expression Regulation, NeoplasticHumansLymphocytes, Tumor-InfiltratingMacrophagesMiddle AgedNeoadjuvant TherapyProgrammed Cell Death 1 ReceptorTriple Negative Breast NeoplasmsConceptsTriple-negative breast cancerPD-L1 expressionNeoadjuvant durvalumabTumor cellsImmune cellsBreast cancerPretreatment core-needle biopsiesPhase I/II clinical trialsPD-L1 protein expressionIMpassion 130 trialCore needle biopsyAmount of CD68Neoadjuvant settingMetastatic settingPD-L1Clinical trialsNeedle biopsyInsufficient tissuePatientsCD68Stromal compartmentQuantitative immunofluorescenceChemotherapyFinal analysisProtein expression