2024
Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study
Puklin L, Irwin M, Sanft T, Ferrucci L, Harrigan M, McGowan C, Cartmel B, Zupa M, Winer E, Deyling M, Ligibel J, Basen-Engquist K, Spiegelman D, Sharifi M. Barriers to and facilitators of improving physical activity and nutrition behaviors during chemotherapy for breast cancer: a sequential mixed methods study. Supportive Care In Cancer 2024, 32: 590. PMID: 39141176, DOI: 10.1007/s00520-024-08789-5.Peer-Reviewed Original ResearchConceptsPhysical activityLifestyle interventionSelf-reported PA questionnaireSelf-reported diet qualityBreast cancerHealthy Eating Index-2015Stage I-III breast cancerBenefits of PASequential mixed methods studyI-III breast cancerChemotherapy-related symptomsMixed methods studyThematic content analysisBehavioral goalsSense of controlBody mass indexPA questionnaireSemi-structured interviewsMean body mass indexTranscribed verbatimIntervention armTailored educationDiet qualityNutritional behaviorMental benefitsEndocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor–Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination
X. C, Suman V, Sanati S, Vij K, Anurag M, Leitch A, Unzeitig G, Hoog J, Fernandez-Martinez A, Fan C, Gibbs R, Watson M, Dockter T, Hahn O, Guenther J, Caudle A, Crouch E, Tiersten A, Mita M, Razaq W, Hieken T, Wang Y, Rimawi M, Weiss A, Winer E, Hunt K, Perou C, Ellis M, Partridge A, Carey L. Endocrine-Sensitive Disease Rate in Postmenopausal Patients With Estrogen Receptor–Rich/ERBB2-Negative Breast Cancer Receiving Neoadjuvant Anastrozole, Fulvestrant, or Their Combination. JAMA Oncology 2024, 10: 362-371. PMID: 38236590, PMCID: PMC10797521, DOI: 10.1001/jamaoncol.2023.6038.Peer-Reviewed Original ResearchConceptsNeoadjuvant endocrine therapyBreast cancerWeek 4Neoadjuvant chemotherapyPostmenopausal womenPAM50 subtypesNonluminal tumorsClinical stage II to IIIRate of pathological complete responseClinical trialsHER2)-negative breast cancerPhase 3 randomized clinical trialLuminal B tumorsPathological complete responseLuminal A tumorsEarly-stage diseaseRandomized clinical trialsStage II to IIIAnastrozole armNeoadjuvant anastrozoleTumor Ki67Postmenopausal patientsB tumorsComplete responseA tumors
2023
Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab
Waks A, Ogayo E, Paré L, Marín-Aguilera M, Brasó-Maristany F, Galván P, Castillo O, Martínez-Sáez O, Vivancos A, Villagrasa P, Villacampa G, Tarantino P, Desai N, Guerriero J, Metzger O, Tung N, Krop I, Parker J, Perou C, Prat A, Winer E, Tolaney S, Mittendorf E. Assessment of the HER2DX Assay in Patients With ERBB2-Positive Breast Cancer Treated With Neoadjuvant Paclitaxel, Trastuzumab, and Pertuzumab. JAMA Oncology 2023, 9: 835-840. PMID: 37103927, PMCID: PMC10141272, DOI: 10.1001/jamaoncol.2023.0181.Peer-Reviewed Original ResearchConceptsPathologic complete responseNeoadjuvant therapyPCR scoresNeoadjuvant paclitaxelBreast cancerPrognostic studiesRisk scoreLikelihood of pCRPretreatment tumor biopsy samplesErbB2-positive breast cancerBaseline tumor samplesLimited clinical featuresFavorable survival outcomesHormone receptor statusPositive breast cancerPrognostic risk scoreTumor biopsy samplesPaclitaxel weeklyComplete responsePCR rateReceptor statusClinical featuresMean ageSurvival outcomesRecurrence eventsAdjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial
Tolaney S, Tarantino P, Graham N, Tayob N, Parè L, Villacampa G, Dang C, Yardley D, Moy B, Marcom P, Albain K, Rugo H, Ellis M, Shapira I, Wolff A, Carey L, Barroso-Sousa R, Villagrasa P, DeMeo M, DiLullo M, Zanudo J, Weiss J, Wagle N, Partridge A, Waks A, Hudis C, Krop I, Burstein H, Prat A, Winer E. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. The Lancet Oncology 2023, 24: 273-285. PMID: 36858723, DOI: 10.1016/s1470-2045(23)00051-7.Peer-Reviewed Original ResearchMeSH KeywordsBreastBreast NeoplasmsFemaleHumansMaleMiddle AgedNeoplasm Recurrence, LocalPaclitaxelTrastuzumabConceptsHER2-positive breast cancerInvasive disease-free survivalDisease-free survivalRecurrence-free intervalAdjuvant paclitaxelBreast cancerEastern Cooperative Oncology Group performance statusInvasive disease-free survival eventsDisease-free survival eventsHormone receptor-positive diseaseNew contralateral breast cancerBreast cancer-specific survivalProtocol-defined treatmentCancer-specific survivalReceptor-positive diseasePhase 2 studyContralateral breast cancerLong-term outcomesAPT trialCause deathEligible patientsIntravenous paclitaxelTrastuzumab weeklyDistant recurrenceIpsilateral recurrenceTucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases
Lin N, Murthy R, Abramson V, Anders C, Bachelot T, Bedard P, Borges V, Cameron D, Carey L, Chien A, Curigliano G, DiGiovanna M, Gelmon K, Hortobagyi G, Hurvitz S, Krop I, Loi S, Loibl S, Mueller V, Oliveira M, Paplomata E, Pegram M, Slamon D, Zelnak A, Ramos J, Feng W, Winer E. Tucatinib vs Placebo, Both in Combination With Trastuzumab and Capecitabine, for Previously Treated ERBB2 (HER2)-Positive Metastatic Breast Cancer in Patients With Brain Metastases. JAMA Oncology 2023, 9: 197-205. PMID: 36454580, PMCID: PMC9716438, DOI: 10.1001/jamaoncol.2022.5610.Peer-Reviewed Original ResearchConceptsErbB2-positive metastatic breast cancerMetastatic breast cancerPlacebo-combination groupPositive metastatic breast cancerNew brain lesionsBrain metastasesOverall survivalSubgroup analysisBrain lesionsBreast cancerIntracranial progression-free survivalPlacebo-controlled clinical trialIntracranial objective response rateStable brain metastasesMedian overall survivalObjective response rateProgression-free survivalExploratory subgroup analysisGreater clinical benefitCNS-PFSHER2CLIMB trialIntracranial outcomesFirst progressionMedian ageClinical benefit
2022
Estimating long-term mortality in women with hormone receptor-positive breast cancer: The ‘ESTIMATE’ tool
Leone JP, Graham N, Tolaney SM, Leone BA, Freedman RA, Hassett MJ, Leone J, Vallejo CT, Winer EP, Lin NU, Tayob N. Estimating long-term mortality in women with hormone receptor-positive breast cancer: The ‘ESTIMATE’ tool. European Journal Of Cancer 2022, 173: 20-29. PMID: 35841843, DOI: 10.1016/j.ejca.2022.06.029.Peer-Reviewed Original ResearchMeSH KeywordsAdultBreastBreast NeoplasmsFemaleHumansMiddle AgedNeoplasm StagingPrognosisSEER ProgramConceptsBreast cancer-specific mortalityHR-positive breast cancerBreast cancerCumulative riskCause mortalityTumor characteristicsRisk of BCSMHormone receptor-positive breast cancerReceptor-positive breast cancerCancer-specific mortalityEnd Results registryLong-term mortalityRisk of deathCancer patient subgroupsPopulation-based riskPathologic variablesInitial diagnosisPatient subgroupsSEER dataPatientsAge groupsCancerMortalityHormone receptorsDiagnosisOverall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer
Hortobagyi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Hart L, Campone M, Petrakova K, Winer EP, Janni W, Conte P, Cameron DA, André F, Arteaga CL, Zarate JP, Chakravartty A, Taran T, Le Gac F, Serra P, O'Shaughnessy J. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. New England Journal Of Medicine 2022, 386: 942-950. PMID: 35263519, DOI: 10.1056/nejmoa2114663.Peer-Reviewed Original ResearchConceptsAdvanced breast cancerSignificant overall survival benefitMedian overall survivalOverall survival benefitProgression-free survivalOverall survivalBreast cancerSurvival benefitHER2-negative advanced breast cancerKey secondary end pointProtocol-specified final analysisLonger progression-free survivalHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Negative advanced breast cancerStratified log-rank testFirst-line ribociclibSecondary end pointsFirst-line therapyNew safety signalsPhase 3 trialGrowth factor receptor 2Kaplan-Meier methodLog-rank testFactor receptor 2
2021
Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study
Krop IE, Im SA, Barrios C, Bonnefoi H, Gralow J, Toi M, Ellis PA, Gianni L, Swain SM, Im YH, De Laurentiis M, Nowecki Z, Huang CS, Fehrenbacher L, Ito Y, Shah J, Boulet T, Liu H, Macharia H, Trask P, Song C, Winer EP, Harbeck N. Trastuzumab Emtansine Plus Pertuzumab Versus Taxane Plus Trastuzumab Plus Pertuzumab After Anthracycline for High-Risk Human Epidermal Growth Factor Receptor 2–Positive Early Breast Cancer: The Phase III KAITLIN Study. Journal Of Clinical Oncology 2021, 40: 438-448. PMID: 34890214, PMCID: PMC8824393, DOI: 10.1200/jco.21.00896.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalOverall populationTrastuzumab emtansineHigh-risk human epidermal growth factor receptorHuman epidermal growth factor receptor 2End pointEpidermal growth factor receptor 2Early breast cancer treatmentHuman epidermal growth factor receptorAnthracycline-based chemotherapyCoprimary end pointsPrimary end pointDisease-free survivalSerious adverse eventsEarly breast cancerGlobal health statusGrowth factor receptor 2Treatment completion ratesStandard of careBreast cancer treatmentFactor receptor 2Epidermal growth factor receptorGrowth factor receptorEndocrine therapyAdverse eventsAdjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03)
Gnant M, Dueck AC, Frantal S, Martin M, Burstein HJ, Greil R, Fox P, Wolff AC, Chan A, Winer EP, Pfeiler G, Miller KD, Colleoni M, Suga JM, Rubovsky G, Bliss JM, Mayer IA, Singer CF, Nowecki Z, Hahn O, Thomson J, Wolmark N, Amillano K, Rugo HS, Steger GG, de Aránguiz B, Haddad TC, Perelló A, Bellet M, Fohler H, Filho O, Jallitsch-Halper A, Solomon K, Schurmans C, Theall KP, Lu DR, Tenner K, Fesl C, DeMichele A, Mayer EL, groups and investigators O. Adjuvant Palbociclib for Early Breast Cancer: The PALLAS Trial Results (ABCSG-42/AFT-05/BIG-14-03). Journal Of Clinical Oncology 2021, 40: 282-293. PMID: 34874182, PMCID: PMC10476784, DOI: 10.1200/jco.21.02554.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, HormonalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantDisease ProgressionDisease-Free SurvivalFemaleHumansMastectomyMiddle AgedNeoadjuvant TherapyNeoplasm StagingPiperazinesProgression-Free SurvivalProspective StudiesProtein Kinase InhibitorsPyridinesTime FactorsConceptsHormone receptor-positive breast cancerInvasive disease-free survivalReceptor-positive breast cancerAdjuvant endocrine therapyCancer-free survivalEndocrine therapyEarly breast cancerBreast cancerAdjuvant palbociclibPALLAS trialEnd pointEarly hormone receptor-positive breast cancerBreast cancer-free survivalDistant recurrence-free survivalHuman epidermal growth factor receptorProtocol-defined analysisStandard endocrine therapyPrimary end pointSecondary end pointsAdvanced breast cancerDisease-free survivalNew safety signalsRecurrence-free survivalEvent end pointsCyclin-dependent kinase 4Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer
Keenan TE, Guerriero JL, Barroso-Sousa R, Li T, O’Meara T, Giobbie-Hurder A, Tayob N, Hu J, Severgnini M, Agudo J, Vaz-Luis I, Anderson L, Attaya V, Park J, Conway J, He MX, Reardon B, Shannon E, Wulf G, Spring LM, Jeselsohn R, Krop I, Lin NU, Partridge A, Winer EP, Mittendorf EA, Liu D, Van Allen EM, Tolaney SM. Molecular correlates of response to eribulin and pembrolizumab in hormone receptor-positive metastatic breast cancer. Nature Communications 2021, 12: 5563. PMID: 34548479, PMCID: PMC8455578, DOI: 10.1038/s41467-021-25769-z.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntibodies, Monoclonal, HumanizedAntigen PresentationAntineoplastic Combined Chemotherapy ProtocolsB7-H1 AntigenBreast NeoplasmsCytokinesDrug Resistance, NeoplasmEstrogensFemaleFuransGene Expression ProfilingGenetic HeterogeneityGenome, HumanGenomicsHumansImmune Checkpoint InhibitorsKetonesLymphocytes, Tumor-InfiltratingMaleMiddle AgedMutationNeoplasm MetastasisReceptors, EstrogenReceptors, ProgesteroneSignal TransductionSurvival RateTreatment OutcomeConceptsImmune checkpoint inhibitorsBreast cancerHormone receptor-positive metastatic breast cancerHormone receptor-positive breast cancerFinal overall survival resultsRandomized phase 2 trialReceptor-positive breast cancerMinimal therapeutic effectPhase 2 trialMetastatic breast cancerOverall survival resultsPre-treatment tumorsCheckpoint inhibitorsCytokine changesICI responseCombination therapyImmune infiltrationImmunoregulatory cytokinesSurvival resultsAntigen presentationTherapeutic effectTherapeutic validationCancerMolecular correlatesTumor heterogeneityChemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial)
Ruddy KJ, Zheng Y, Tayob N, Hu J, Dang CT, Yardley DA, Isakoff SJ, Valero VV, Faggen MG, Mulvey TM, Bose R, Sella T, Weckstein DJ, Wolff AC, Reeder-Hayes KE, Rugo HS, Ramaswamy B, Zuckerman DS, Hart LL, Gadi VK, Constantine M, Cheng KL, Briccetti FM, Schneider BP, Merrill Garrett A, Kelly Marcom P, Albain KS, DeFusco PA, Tung NM, Ardman BM, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu MC, Rosenberg S, DeMeo MK, Burstein HJ, Winer EP, Krop IE, Partridge AH, Tolaney SM. Chemotherapy-related amenorrhea (CRA) after adjuvant ado-trastuzumab emtansine (T-DM1) compared to paclitaxel in combination with trastuzumab (TH) (TBCRC033: ATEMPT Trial). Breast Cancer Research And Treatment 2021, 189: 103-110. PMID: 34120223, DOI: 10.1007/s10549-021-06267-8.Peer-Reviewed Original ResearchConceptsChemotherapy-related amenorrheaEarly-stage breast cancerRisk of infertilityAdo-trastuzumab emtansineT-DM1Gonadotropin-releasing hormone agonistAdjuvant T-DM1T-DM1 3.6Amenorrhea ratesPermanent menopauseStandard HER2Chemotherapy regimensPrimary endpointProtocol therapyMedian ageOvarian toxicityPremature menopauseHormone agonistBreast cancerMenstrual dataMonthsAmenorrheaEmtansineMenopauseTrastuzumabAdjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial
Tolaney SM, Tayob N, Dang C, Yardley DA, Isakoff SJ, Valero V, Faggen M, Mulvey T, Bose R, Hu J, Weckstein D, Wolff AC, Reeder-Hayes K, Rugo HS, Ramaswamy B, Zuckerman D, Hart L, Gadi VK, Constantine M, Cheng K, Briccetti F, Schneider B, Garrett AM, Marcom K, Albain K, DeFusco P, Tung N, Ardman B, Nanda R, Jankowitz RC, Rimawi M, Abramson V, Pohlmann PR, Van Poznak C, Forero-Torres A, Liu M, Ruddy K, Zheng Y, Rosenberg SM, Gelber RD, Trippa L, Barry W, DeMeo M, Burstein H, Partridge A, Winer EP, Krop I. Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial. Journal Of Clinical Oncology 2021, 39: 2375-2385. PMID: 34077270, DOI: 10.1200/jco.20.03398.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalT-DM1Breast cancerStage IStage I HER2-positive breast cancerHER2-positive breast cancerHuman epidermal growth factor receptorAdjuvant T-DM1Co-primary objectivesDisease-free survivalPatient-reported outcomesEpidermal growth factor receptorGrowth factor receptorProtocol therapyAnalysis populationTrastuzumab emtansineClinical trialsRelevant toxicityPatientsFactor receptorLess toxicityWeeksTrastuzumabCancerPaclitaxelGenomic features of rapid versus late relapse in triple negative breast cancer
Zhang Y, Asad S, Weber Z, Tallman D, Nock W, Wyse M, Bey JF, Dean KL, Adams EJ, Stockard S, Singh J, Winer EP, Lin NU, Jiang YZ, Ma D, Wang P, Shi L, Huang W, Shao ZM, Cherian M, Lustberg MB, Ramaswamy B, Sardesai S, VanDeusen J, Williams N, Wesolowski R, Obeng-Gyasi S, Sizemore GM, Sizemore ST, Verschraegen C, Stover DG. Genomic features of rapid versus late relapse in triple negative breast cancer. BMC Cancer 2021, 21: 568. PMID: 34006255, PMCID: PMC8130400, DOI: 10.1186/s12885-021-08320-7.Peer-Reviewed Original ResearchMeSH KeywordsAdultBiomarkers, TumorChemotherapy, AdjuvantDatasets as TopicDisease-Free SurvivalDNA Copy Number VariationsFemaleFollow-Up StudiesGene Expression ProfilingGene Expression Regulation, NeoplasticHumansLogistic ModelsMastectomyMiddle AgedModels, GeneticMutationNeoadjuvant TherapyNeoplasm Recurrence, LocalPrognosisRisk AssessmentTime FactorsTriple Negative Breast NeoplasmsConceptsLate relapseRapid relapseImmune signaturesBreast cancerAnti-tumor CD8 T cellsBackgroundTriple-negative breast cancerTriple-negative breast cancerCD8 T cellsTumor mutation burdenIndependent validation cohortNegative breast cancerFisher's exact testPearson's chi-squared testChi-squared testLogistic regression modelsLuminal signaturePrimary TNBCTNBC subsetImmune subsetsClinical featuresValidation cohortWhole-genome copy numberPrimary tumorM1 macrophagesT cellsUpdated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer
Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer. Journal Of Clinical Oncology 2021, 39: 2247-2256. PMID: 33999652, PMCID: PMC8260904, DOI: 10.1200/jco.21.00280.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsChemotherapy, AdjuvantFemaleFluorodeoxyglucose F18HumansMiddle AgedNeoadjuvant TherapyPositron Emission Tomography Computed TomographyPredictive Value of TestsRadiopharmaceuticalsReceptor, ErbB-2Time FactorsTrastuzumabTreatment OutcomeUnited StatesConceptsPositron emission tomography-computed tomographyFluorodeoxyglucose positron emission tomography-computed tomographyHER2-positive breast cancerEmission tomography-computed tomographyPathologic complete responseTomography-computed tomographyStandardized uptake valueBreast cancerComplete responseUptake valuePercent changeOne-sided type ITumor maximum standardized uptake valueHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Maximum standardized uptake valuePathological complete responseGrowth factor receptor 2Median percent reductionPositive breast cancerTailoring of therapyLean body massReceiver operator characteristic analysisFactor receptor 2Operator characteristic analysisImpact of Cancer History on Outcomes Among Hospitalized Patients with COVID-19
Klein IA, Rosenberg SM, Reynolds KL, Zubiri L, Rosovsky R, Piper-Vallillo A, Gao X, Boland G, Bardia A, Gaither R, Freeman H, Kirkner GJ, Rhee C, Klompas M, Baker MA, Wadleigh M, Winer EP, Kotton CN, Partridge AH. Impact of Cancer History on Outcomes Among Hospitalized Patients with COVID-19. The Oncologist 2021, 26: 685-693. PMID: 33856099, PMCID: PMC8251362, DOI: 10.1002/onco.13794.Peer-Reviewed Original ResearchConceptsHistory of cancerIndependent risk factorDeath/hospiceSevere COVID-19Survivors of cancerHospitalized patientsCancer historyActive cancerRisk factorsCurrent cancer diagnosisCancer diagnosisCOVID-19Laboratory-confirmed COVID-19Intensive care unit admissionCare unit admissionOdds of intubationCancer-directed therapySystemic cancer therapyStandard anticancer therapiesRecent cancer treatmentUnit admissionHospice admissionMedian ageMedian timeMultivariable analysisImpact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab
Filho OM, Viale G, Stein S, Trippa L, Yardley DA, Mayer IA, Abramson VG, Arteaga CL, Spring LM, Waks AG, Wrabel E, DeMeo MK, Bardia A, Dell'Orto P, Russo L, King TA, Polyak K, Michor F, Winer EP, Krop IE. Impact of HER2 heterogeneity on treatment response of early-stage HER2-positive breast cancer: phase II neoadjuvant clinical trial of T-DM1 combined with pertuzumab. Cancer Discovery 2021, 11: candisc.1557.2020. PMID: 33941592, PMCID: PMC8598376, DOI: 10.1158/2159-8290.cd-20-1557.Peer-Reviewed Original ResearchConceptsHER2-positive breast cancerHER2 heterogeneityBreast cancerEarly-stage HER2-positive breast cancerHER2-positive early-stage breast cancerTherapeutic resistancePathologic complete response rateEarly-stage breast cancerNeoadjuvant clinical trialsComplete response rateSubset of patientsHER2 therapyPretreatment biopsiesEvaluable casesCure rateT-DM1Trastuzumab emtansineClinical trialsTreatment strategiesTreatment responseTreatment selectionResponse rateRelated commentaryTherapyIssue featureThe impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer
Janiszewska M, Stein S, Filho O, Eng J, Kingston NL, Harper NW, Rye IH, Alečković M, Trinh A, Murphy KC, Marangoni E, Cristea S, Oakes B, Winer EP, Krop I, Russnes HG, Spellman PT, Bucher E, Hu Z, Chin K, Gray JW, Michor F, Polyak K. The impact of tumor epithelial and microenvironmental heterogeneity on treatment responses in HER2-positive breast cancer. JCI Insight 2021, 6: e147617. PMID: 33886505, PMCID: PMC8262355, DOI: 10.1172/jci.insight.147617.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalBreast NeoplasmsClass I Phosphatidylinositol 3-KinasesDNA Copy Number VariationsDrug Resistance, NeoplasmEpithelial CellsFemaleFibroblastsHumansMacrophagesMiddle AgedMutationNeoplasm TransplantationReceptor, ErbB-2TrastuzumabTumor MicroenvironmentVesicular Transport ProteinsConceptsBreast cancerTherapeutic resistanceHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Patient-derived xenograft modelsLymphatic vessel endothelial hyaluronan receptorHER2-targeted therapiesGrowth factor receptor 2Impact of tumorFibroblastic reticular cellsFactor receptor 2Tumor epithelial cellsIntratumor heterogeneityDivergent cellular phenotypesResistance-conferring mutationsClinical outcomesPIK3CA mutationsTreatment responseClinical challengeDifferent therapiesFrequency of cellsXenograft modelReceptor 2Stromal determinantsPhysical Activity, Weight, and Outcomes in Patients Receiving Chemotherapy for Metastatic Breast Cancer (C40502/Alliance)
Ligibel JA, Huebner L, Rugo HS, Burstein HJ, Toppmeyer DL, Anders CK, Ma C, Barry WT, Suman V, Carey LA, Partridge AH, Hudis CA, Winer EP. Physical Activity, Weight, and Outcomes in Patients Receiving Chemotherapy for Metastatic Breast Cancer (C40502/Alliance). JNCI Cancer Spectrum 2021, 5: pkab025-. PMID: 33981951, PMCID: PMC8103727, DOI: 10.1093/jncics/pkab025.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsBevacizumabBody HeightBody Mass IndexBody WeightBreast NeoplasmsEpothilonesExerciseFemaleHumansMiddle AgedObesityPaclitaxelProgression-Free SurvivalProportional Hazards ModelsTreatment OutcomeYoung AdultConceptsProgression-free survivalMetastatic breast cancerBody mass indexOverall survivalPhysical activityBreast cancerMass indexMET hoursFirst-line taxane-based chemotherapyHormone receptor-positive cancersBaseline body mass indexFirst-line chemotherapyTaxane-based chemotherapyReceptor-positive cancersRecreational physical activityRates of obesityMetastatic diseaseCox modelingMedian ageOverall mortalityRandomized trialsTask hoursMetabolic equivalentsPatientsCancerA Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer
Bellon JR, Chen YH, Rees R, Taghian AG, Wong JS, Punglia RS, Shiloh RY, Warren LEG, Krishnan MS, Phillips J, Pretz J, Jimenez R, Macausland S, Pashtan I, Andrews C, Isakoff SJ, Winer EP, Tolaney SM. A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: 45-52. PMID: 33713742, DOI: 10.1016/j.ijrobp.2021.03.002.Peer-Reviewed Original ResearchConceptsTriple-negative breast cancerBreast-conserving therapyDose-limiting toxicityBCT cohortRadiation therapyConcurrent cisplatinMastectomy cohortBreast cancerEarly-stage triple-negative breast cancerThree-year disease-free survivalPhase 1 dose-escalation trialStage IILocal-regional recurrence ratePhase 2 doseAdjuvant radiation therapyDisease-free survivalDose-escalation trialPhase 1b trialDose of cisplatinHER2-positive tumorsEligible patientsUrinary infectionAdditional patientsDose escalationRecurrence ratePembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial
Winer EP, Lipatov O, Im SA, Goncalves A, Muñoz-Couselo E, Lee KS, Schmid P, Tamura K, Testa L, Witzel I, Ohtani S, Turner N, Zambelli S, Harbeck N, Andre F, Dent R, Zhou X, Karantza V, Mejia J, Cortes J, investigators K. Pembrolizumab versus investigator-choice chemotherapy for metastatic triple-negative breast cancer (KEYNOTE-119): a randomised, open-label, phase 3 trial. The Lancet Oncology 2021, 22: 499-511. PMID: 33676601, DOI: 10.1016/s1470-2045(20)30754-3.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerTriple-negative breast cancerCombined positive scoreMedian overall survivalPD-L1 combined positive scoreTreatment-related adverse eventsPhase 3 trialChemotherapy groupOverall survivalPembrolizumab groupBreast cancerAdverse eventsPrimary endpointMetastatic diseaseEastern Cooperative Oncology Group performance statusPD-L1 tumor statusCommon grade 3Durable antitumour activityInvestigator-choice chemotherapyPrevious systemic treatmentSerious adverse eventsThird-line treatmentSubpopulation of patientsTreatment of patientsSingle-drug chemotherapy