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 advances
2022
Pathologic 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 paclitaxelDurvalumab 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 cases
2017
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.
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 paclitaxelEffects 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 PCRChemotherapyTumors
2016
T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
Dzimitrowicz H, Berger M, Vargo C, Hood A, Abdelghany O, Raghavendra AS, Tripathy D, Valero V, Hatzis C, Pusztai L, Murthy R. T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2–Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab. Journal Of Clinical Oncology 2016, 34: 3511-3517. PMID: 27298406, PMCID: PMC6075965, DOI: 10.1200/jco.2016.67.3624.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAged, 80 and overAntibodies, Monoclonal, HumanizedAntineoplastic AgentsBreast NeoplasmsDisease ProgressionHumansMaytansineMiddle AgedNeoplasm MetastasisReceptor, ErbB-2Response Evaluation Criteria in Solid TumorsRetreatmentRetrospective StudiesTrastuzumabConceptsMetastatic breast cancerHER2-positive metastatic breast cancerTumor response rateT-DM1Prior pertuzumabCancer HospitalBreast cancerMetastatic human epidermal growth factor receptorResponse rateStandard first-line therapyHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2MD Anderson Cancer CenterHuman epidermal growth factor receptorFourth-line treatmentSmilow Cancer HospitalT-DM1 activityFirst-line therapyThird of patientsGrowth factor receptor 2Contemporary patient populationJames Cancer HospitalResults of patientsAdo-trastuzumab emtansineElectronic pharmacy records
2015
Predictive and Prognostic Value of the TauProtein in Breast Cancer.
Bonneau C, Gurard-Levin ZA, Andre F, Pusztai L, Rouzier R. Predictive and Prognostic Value of the TauProtein in Breast Cancer. Anticancer Research 2015, 35: 5179-84. PMID: 26408675.Peer-Reviewed Original ResearchConceptsBreast cancerTau protein expressionTau proteinPrognostic valueTau expressionHuman epidermal growth factor receptor 2 (HER2) expressionEpidermal growth factor receptor 2 expressionLow tau expressionProtein expressionSubset of patientsReceptor 2 expressionIncreased response rateEffects of taxanesNodal statusBetter prognosisPredictive markerTaxane resistanceChemotherapy sensitivityPredictive valueResponse ratePubMed databaseDrug resistanceCancerHormone receptorsTaxanesCCR 20th Anniversary Commentary: Divide and Conquer—Breast Cancer Subtypes and Response to Therapy
Pusztai L, Rouzier R, Symmans WF. CCR 20th Anniversary Commentary: Divide and Conquer—Breast Cancer Subtypes and Response to Therapy. Clinical Cancer Research 2015, 21: 3575-3577. PMID: 26275950, DOI: 10.1158/1078-0432.ccr-14-3121.Peer-Reviewed Original ResearchConceptsBreast cancerPathologic complete response rateTriple-negative breast cancerAdjuvant treatment optionsResidual invasive diseaseComplete response rateHER2-positive cancersDifferent molecular subtypesClin Cancer ResClinical cancer researchAnniversary CommentaryNeoadjuvant therapyTreatment optionsInvasive diseaseClinical trialsMolecular subtypesResponse rateCancer subtypesCancer ResExtent of responseCancerSubtypesTherapyCancer researchChemotherapyA network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer
Generali D, Venturini S, Rognoni C, Ciani O, Pusztai L, Loi S, Jerusalem G, Bottini A, Tarricone R. A network meta-analysis of everolimus plus exemestane versus chemotherapy in the first- and second-line treatment of estrogen receptor-positive metastatic breast cancer. Breast Cancer Research And Treatment 2015, 152: 95-117. PMID: 26044370, DOI: 10.1007/s10549-015-3453-9.Peer-Reviewed Original ResearchConceptsProgression-free survivalMetastatic breast cancerHazard ratioMegestrol acetateResponse rateBreast cancerEstrogen receptor-positive metastatic breast cancerPFS/TTPSecond-line therapySecond-line treatmentToxicity of chemotherapyOverall response rateBetter response rateCapecitabineStandard pairwiseTamoxifenSunitinibChemotherapyTTP differenceMultiple treatmentsNMAIndividual studiesEverolimusExemestaneCancer
2013
Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas
Delpech Y, Coutant C, Hsu L, Barranger E, Iwamoto T, Barcenas CH, Hortobagyi GN, Rouzier R, Esteva FJ, Pusztai L. Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas. British Journal Of Cancer 2013, 108: 285-291. PMID: 23299541, PMCID: PMC3566807, DOI: 10.1038/bjc.2012.557.Peer-Reviewed Original ResearchConceptsInvasive ductal carcinomaBreast-conserving surgeryNeoadjuvant chemotherapyPure lobular carcinomaLobular carcinomaClinical benefitTumor sizeER-positive invasive ductal carcinomasLower pathological complete response rateResponse ratePathological complete response ratePathological response rateComplete response rateGood clinical responsePathological complete responseType of chemotherapyPositive surgical marginsSurgical resection marginsClinical responseNodal statusComplete responseResection marginsSurgical marginsDuctal carcinomaPositive margins
2010
Estrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials
Andre F, Broglio K, Pusztai L, Berrada N, Mackey JR, Nabholtz JM, Chan S, Hortobagyi GN. Estrogen Receptor Expression and Docetaxel Efficacy in Patients with Metastatic Breast Cancer: A Pooled Analysis of Four Randomized Trials. The Oncologist 2010, 15: 476-483. PMID: 20421265, PMCID: PMC3227977, DOI: 10.1634/theoncologist.2009-0150.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerEfficacy of docetaxelBreast cancerHigh response rateER expressionResponse rateEstrogen receptorHazard ratioRandomized trialsDisease progressionProgression-free survival timeCox proportional hazards modelDocetaxel-based regimenEstrogen receptor expressionProportional hazards modelEffect of docetaxelER- diseasePFS timeDocetaxel efficacyPooled analysisTumor responseReceptor expressionSurvival timeLower riskHazards model
2009
Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials
Mazouni C, André F, Broglio K, Pusztai L, Hortobagyi G. Estrogen receptor expression and docetaxel efficacy in patients with metastatic breast cancer: A pooled analysis of four randomized trials. Journal Of Clinical Oncology 2009, 27: 1046-1046. DOI: 10.1200/jco.2009.27.15_suppl.1046.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalER-negative diseaseEfficacy of docetaxelBreast cancerER expressionResponse rateRandomized trialsDisease progressionEstrogen receptor-positive metastatic breast cancerPositive metastatic breast cancerCox proportional hazards modelTumor response rateER-positive patientsER-negative cancersEstrogen receptor expressionProportional hazards modelEffect of docetaxelHazard ratioDocetaxel efficacyPooled analysisTumor responseReceptor expressionHazards modelPatientsEvaluation of serum profiles changes after neoadjuvant chemotherapy for breast cancer using MALDI-TOF/MS procedure
Hawke D, Mazouni C, André F, Baggerly K, Baggerly K, Tsavachidis S, Buzdar A, Martin P, Kobayashi R, Pusztai L. Evaluation of serum profiles changes after neoadjuvant chemotherapy for breast cancer using MALDI-TOF/MS procedure. Journal Of Clinical Oncology 2009, 27: e22072-e22072. DOI: 10.1200/jco.2009.27.15_suppl.e22072.Peer-Reviewed Original ResearchNeoadjuvant chemotherapyBreast cancerPrimary chemotherapyHER2-positive patientsPathological complete responseBreast cancer cohortPositive patientsComplete responseUnnecessary toxicityResidual diseaseTumor responseCancer cohortBlood samplesChemotherapyResponse rateTreatment cyclesPosttreatment samplesCancerSerum samplesRD groupSignificant financial relationshipPatientsProfile changesRespondersTotal
2008
Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab
Peintinger F, Buzdar AU, Kuerer HM, Mejia JA, Hatzis C, Gonzalez-Angulo AM, Pusztai L, Esteva FJ, Dawood SS, Green MC, Hortobagyi GN, Symmans WF. Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab. Annals Of Oncology 2008, 19: 2020-2025. PMID: 18667396, PMCID: PMC2733116, DOI: 10.1093/annonc/mdn427.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsClinical Trials as TopicCyclophosphamideDoxorubicinEpirubicinFemaleFluorouracilHumansMiddle AgedNeoadjuvant TherapyNeoplasm, ResidualNeoplasms, Hormone-DependentPaclitaxelRandomized Controlled Trials as TopicReceptor, ErbB-2Receptors, EstrogenReceptors, ProgesteroneTrastuzumabConceptsHER2-positive breast cancerHormone receptor statusPathologic complete responseResidual cancer burdenPathologic responseBreast cancerNeoadjuvant chemotherapyReceptor statusExtensive residual diseaseHR-negative cancerHR-positive cancersPathologic response rateAddition of trastuzumabNeo-adjuvant chemotherapyStandard neoadjuvant chemotherapyFEC chemotherapyHR-/HER2Pathologic reviewComplete responseLymph nodesCancer burdenResidual diseasePrimary tumorChemotherapyResponse rate
2007
Pharmacogenomic Predictor Discovery in Phase II Clinical Trials for Breast Cancer
Pusztai L, Anderson K, Hess KR. Pharmacogenomic Predictor Discovery in Phase II Clinical Trials for Breast Cancer. Clinical Cancer Research 2007, 13: 6080-6086. PMID: 17947471, DOI: 10.1158/1078-0432.ccr-07-0809.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBreast NeoplasmsClinical Trials, Phase II as TopicGene Expression ProfilingGene Expression Regulation, NeoplasticHumansIn Situ Hybridization, FluorescenceOligonucleotide Array Sequence AnalysisPharmacogeneticsProbabilityRNA, MessengerTissue DistributionTrastuzumabConceptsPhase II studyPhase II trialII trialII studyBreast cancerTwo-stage phase II trialPhase II clinical trialPhase II trial designPredictors of responseMarker-positive patientsPhase II designUnselected patientsPatient populationClinical trialsTrastuzumab responseInsufficient responseTrial designResponse markersSame drugResponse rateMarker testingPotential predictorsMarker assessmentTrialsPatients