2024
Peripheral 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, 1-9. 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 responsePhase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer.
Chavez-MacGregor M, Miao J, Pusztai L, Goetz M, Rastogi P, Ganz P, Mamounas E, Paik S, Bandos H, Razaq W, O'Dea A, Kaklamani V, Silber A, Flaum L, Andreopoulou E, Wendt A, Carney J, Sharma P, Gralow J, Lew D, Barlow W, Hortobagyi G. Phase III Randomized, Placebo-Controlled Trial of Endocrine Therapy ± 1 Year of Everolimus in Patients With High-Risk, Hormone Receptor-Positive, Early-Stage Breast Cancer. Journal Of Clinical Oncology 2024, jco2302344. PMID: 38833643, DOI: 10.1200/jco.23.02344.Peer-Reviewed Original ResearchInvasive disease-free survivalHormone receptor-positiveEndocrine therapyOverall survivalBreast cancerHazard ratioReceptor-positiveHigh riskSubset analysisHormone receptor-positive metastatic breast cancerRisk groupsHormone receptor-positive BCEarly-stage breast cancerStratified log-rank testProgression-free survivalEfficacy of everolimusDisease-free survivalMetastatic breast cancerPlacebo-controlled trialSecondary end pointsLog-rank testHighest grade 3Treatment completion ratesPhase IIIEverolimus arm
2023
Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study
Sanft T, Harrigan M, McGowan C, Cartmel B, Zupa M, Li F, Ferrucci L, Puklin L, Cao A, Nguyen T, Neuhouser M, Hershman D, Basen-Engquist K, Jones B, Knobf T, Chagpar A, Silber A, Tanasijevic A, Ligibel J, Irwin M. Randomized Trial of Exercise and Nutrition on Chemotherapy Completion and Pathologic Complete Response in Women With Breast Cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis Study. Journal Of Clinical Oncology 2023, 41: 5285-5295. PMID: 37656930, PMCID: PMC10691793, DOI: 10.1200/jco.23.00871.Peer-Reviewed Original ResearchConceptsRelative dose intensityPathologic complete responseProportion of patientsBreast cancerNeoadjuvant chemotherapyChemotherapy completionComplete responseNutrition interventionsHigher pathologic complete responseHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Triple-negative breast cancerChemotherapy dose adjustmentsHome-based exerciseGrowth factor receptor 2Breast cancer outcomesEffects of exerciseFactor receptor 2Electronic medical recordsChi-square testUsual careDose intensityExercise interventionDose adjustmentRandomized trialsDemographic and clinical factors associated with cardiovascular events in elderly long-term survivors of breast cancer.
Westvold S, KC M, Fan J, Hyslop T, Spees L, Wang S, Silber A, Oeffinger K, Dinan M. Demographic and clinical factors associated with cardiovascular events in elderly long-term survivors of breast cancer. Journal Of Clinical Oncology 2023, 41: e24105-e24105. DOI: 10.1200/jco.2023.41.16_suppl.e24105.Peer-Reviewed Original ResearchLong-term breast cancer survivorsBreast cancer survivorsLong-term survivorsCardiovascular diseaseCancer survivorsHigh riskCancer stageRace/ethnicityClinical characteristicsDiagnosis yearBreast cancerEvidence of CVDNon-Hispanic black patientsNon-metastatic breast cancerLong-term cancer survivorsCox proportional hazards modelCurative-intent surgeryCVD hazard ratiosNon-oncologic outcomesCancer-specific survivalStage III diseaseInitial cancer diagnosisDiagnosis of CVDRace/ethnicity groupsChi-square test
2022
Mucosal haemangioma in the setting of treatment with trastuzumab emtansine (T‐DM1)
Belzer A, Silber A, Mehra S, Gilani S, Leventhal JS. Mucosal haemangioma in the setting of treatment with trastuzumab emtansine (T‐DM1). British Journal Of Dermatology 2022, 187: e168-e168. PMID: 35633104, DOI: 10.1111/bjd.21654.Peer-Reviewed Case Reports and Technical NotesClinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm DL, Pusztai L. Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. Clinical Cancer Research 2022, 28: 3720-3728. PMID: 35903931, PMCID: PMC9444984, DOI: 10.1158/1078-0432.ccr-22-0862.Peer-Reviewed Original ResearchConceptsImmune-related adverse eventsTriple-negative breast cancerNon-AA patientsEvent-free survivalPhase I/II clinical trialsClinical trialsNeoadjuvant chemotherapyOverall survivalAA patientsEarly-stage triple-negative breast cancerIncidence of irAEsPathologic complete response rateSignificant associationMultivariate logistic regression analysisTumor-infiltrating lymphocyte countsComplete response ratePrimary efficacy endpointPD-L1 statusProportional hazards modelLogistic regression analysisAfrican American womenEFS ratesNeoadjuvant immunotherapyEfficacy endpointAdverse eventsRandomized trial of diet and exercise on chemotherapy completion in women with breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) study.
Sanft T, Harrigan M, Cartmel B, Li F, Zupa M, McGowan C, Ferrucci L, Puklin L, Nguyen T, Tanasijevic A, Neuhouser M, Hershman D, Basen-Engquist K, Jones B, Knobf M, Chagpar A, Silber A, Ligibel J, Irwin M. Randomized trial of diet and exercise on chemotherapy completion in women with breast cancer: The Lifestyle, Exercise, and Nutrition Early After Diagnosis (LEANer) study. Journal Of Clinical Oncology 2022, 40: 12007-12007. DOI: 10.1200/jco.2022.40.16_suppl.12007.Peer-Reviewed Original ResearchRelative dose intensityHigh relative dose intensityBreast cancerDose-response effectPhysical activityPA interventionsNeoadjuvant chemotherapyChemotherapy completionDiet qualityStage I breast cancerEndocrine therapy adherenceTrial of dietDifferent chemotherapy regimensI breast cancerBody mass indexPatient-reported outcomesHealthy Eating IndexBetter diet qualityHigh physical activityMore physical activityElectronic medical recordsChi-square testUC participantsChemotherapy regimensSecondary endpointsClinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC.
Foldi J, Kahn A, Silber A, Qing T, Reisenbichler E, Fischbach N, Persico J, Adelson K, Katoch A, Chagpar A, Park T, Blanchard A, Blenman K, Rimm D, Pusztai L. Clinical outcomes and immune markers by race in a phase I/II clinical trial of durvalumab concomitant with neoadjuvant chemotherapy in early-stage TNBC. Journal Of Clinical Oncology 2022, 40: 516-516. DOI: 10.1200/jco.2022.40.16_suppl.516.Peer-Reviewed Original ResearchImmune-related adverse eventsTriple-negative breast cancerMultivariate logistic regression analysisPD-L1 statusLogistic regression analysisAA raceOverall survivalPathologic responseClinical trialsBreast cancerEarly-stage triple-negative breast cancerIncidence of irAEsPhase I/II trialPathologic complete response rateSignificant associationPhase I/II clinical trialsBaseline body mass indexSafety of immunotherapyWeekly nab-paclitaxelCharlson Comorbidity IndexComplete response ratePrimary efficacy endpointPD-L1 expressionBody mass indexBreast cancer recurrencePredictive 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 ResearchConceptsBasal-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 cycleAuthor Correction: Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
Foldi J, Silber A, Reisenbichler E, Singh K, Fischbach N, Persico J, Adelson K, Katoch A, Horowitz N, Lannin D, Chagpar A, Park T, Marczyk M, Frederick C, Burrello T, Ibrahim E, Qing T, Bai Y, Blenman K, Rimm DL, Pusztai L. Author Correction: Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2022, 8: 17. PMID: 35115541, PMCID: PMC8814070, DOI: 10.1038/s41523-022-00392-3.Peer-Reviewed Original Research
2021
A Phase II Study Evaluating Orteronel, an Inhibitor of Androgen Biosynthesis, in Patients With Androgen Receptor (AR)-Expressing Metastatic Breast Cancer (MBC)
Yardley DA, Young RR, Adelson KB, Silber AL, Najera JE, Daniel DB, Peacock N, Finney L, Hoekstra SJ, Shastry M, Hainsworth JD, Burris HA. A Phase II Study Evaluating Orteronel, an Inhibitor of Androgen Biosynthesis, in Patients With Androgen Receptor (AR)-Expressing Metastatic Breast Cancer (MBC). Clinical Breast Cancer 2021, 22: 269-278. PMID: 34824002, DOI: 10.1016/j.clbc.2021.10.011.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerCohort 2Cohort 1Breast cancerAndrogen biosynthesisAmylase/lipaseLimited clinical activityPrior chemotherapy regimenPrior chemotherapy regimensMedian treatment durationNausea/vomitingChemotherapy regimenChemotherapy regimensPrimary endpointObjective responseOverall survivalFemale patientsAndrogen receptorClinical activityGrade 3Targetable pathwaysPatientsTherapeutic targetAR modulationTreatment durationEffect of healthy diet and exercise on chemotherapy completion rate in women with breast cancer: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) study: Study protocol for a randomized clinical trial
Sanft T, Harrigan M, Cartmel B, Ferrucci LM, Li FY, McGowan C, Zupa M, Nguyen TH, Ligibel J, Neuhouser ML, Hershman DL, Basen-Engquist K, Jones B, Knobf T, Chagpar A, Silber A, Irwin ML. Effect of healthy diet and exercise on chemotherapy completion rate in women with breast cancer: The Lifestyle, Exercise and Nutrition Early after Diagnosis (LEANer) study: Study protocol for a randomized clinical trial. Contemporary Clinical Trials 2021, 109: 106508. PMID: 34274495, PMCID: PMC10424280, DOI: 10.1016/j.cct.2021.106508.Peer-Reviewed Original ResearchConceptsChemotherapy completion rateTreatment-related side effectsPhysical activity guidelinesBreast cancerActivity guidelinesCancer survivorsSide effectsWorld Cancer Research FundUsual care control groupCompletion ratesEndocrine therapy adherenceCare control groupHealthy lifestyle interventionRandomized clinical trialsPatient reported outcomesPhysical activity interventionsBreast cancer treatmentAmerican Cancer SocietyBreast cancer prognosisCancer Research FundElectronic medical recordsOncology nutritionTreating oncologistSecondary endpointsChemotherapy sessionNeoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer
Foldi J, Silber A, Reisenbichler E, Singh K, Fischbach N, Persico J, Adelson K, Katoch A, Horowitz N, Lannin D, Chagpar A, Park T, Marczyk M, Frederick C, Burrello T, Ibrahim E, Qing T, Bai Y, Blenman K, Rimm DL, Pusztai L. Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Npj Breast Cancer 2021, 7: 9. PMID: 33558513, PMCID: PMC7870853, DOI: 10.1038/s41523-021-00219-7.Peer-Reviewed Original ResearchStromal tumor-infiltrating lymphocytesWeekly nab-paclitaxelTriple-negative breast cancerPD-L1Nab-paclitaxelAdverse eventsBreast cancerGrade 3/4 treatment-related adverse eventsPhase I/II trialGrade 3/4 adverse eventsTreatment-related adverse eventsDoxorubicin/cyclophosphamidePhase II studyGuillain-Barre syndromeMononuclear inflammatory cellsPathologic complete responseTumor-infiltrating lymphocytesTumor cell stainingEvaluable patientsNeoadjuvant durvalumabSP263 antibodyII trialNeoadjuvant chemotherapyNeoadjuvant therapyPrimary endpoint
2020
Increasing accrual of minority patients in breast cancer clinical trials
Trant AA, Walz L, Allen W, DeJesus J, Hatzis C, Silber A. Increasing accrual of minority patients in breast cancer clinical trials. Breast Cancer Research And Treatment 2020, 184: 499-505. PMID: 32840699, DOI: 10.1007/s10549-020-05873-2.Peer-Reviewed Original ResearchConceptsClinical trialsHispanic patientsCancer CenterEligibility criteriaWhite patientsMinority patientsYale Cancer CenterBreast cancer clinical trialsConnecticut Tumor RegistryLiver function testsBreast cancer trialsCancer clinical trialsParticipation of patientsClinical Trials OfficeGrand rounds presentationTumor RegistryCenter patientsFunction testsChronic conditionsCancer trialsPatient educationPatientsTrials InitiativeTrials OfficeHealthcare providers
2019
Quantitative assessment of immune cell populations and associations with clinical outcomes in African-American (AA) versus Caucasian triple-negative breast cancer (TNBC).
O'Meara T, Yaghoobi V, Blenman K, Pelekanou V, Silber A, Rimm D, Pusztai L. Quantitative assessment of immune cell populations and associations with clinical outcomes in African-American (AA) versus Caucasian triple-negative breast cancer (TNBC). Journal Of Clinical Oncology 2019, 37: e14180-e14180. DOI: 10.1200/jco.2019.37.15_suppl.e14180.Peer-Reviewed Original ResearchTriple-negative breast cancerDisease-free survivalBetter disease-free survivalPD-L1 expressionCD68 expressionAA TNBCStromal PD-L1 expressionPD-L1 protein expressionCaucasian casesHigher TIL countsTumor immune microenvironmentImmune cell populationsHigh CD68 expressionHigh CD68Similar CD8Stromal TILsClinical characteristicsDiagnosis dateTIL countPD-L1Clinical outcomesPredictive factorsCD8 expressionClinical variablesImmune microenvironment
2017
Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial.
Pusztai L, Silber A, Hofstatter E, Chung G, Horowitz N, Lannin D, Killelea B, Chagpar A, Szekely B, Frederick C, Rispoli L, DiGiovanna M. Safety of MEDI4736 (anti-PD-L1 antibody) administered concomitant with weekly nab-paclitaxel and dose dense doxorubicin/cyclophosphamide (ddAC) as neoadjuvant chemotherapy for stage I-III triple negative breast cancer (TNBC): A Phase I/II trial. Journal Of Clinical Oncology 2017, 35: 572-572. DOI: 10.1200/jco.2017.35.15_suppl.572.Peer-Reviewed Original ResearchImmune related adverse eventsTriple-negative breast cancerWeekly nab-paclitaxelWeeks of therapyNeoadjuvant chemotherapyDose levelsNab-paclitaxelPhase I/II trialPathologic complete response rateChest X-ray abnormalitiesDoxorubicin/cyclophosphamidePhase I toxicityComplete response rateImmune checkpoint inhibitorsPhase I portionRelated adverse eventsPhase II portionPhase I partX-ray abnormalitiesNegative breast cancerSequential taxaneAnthracycline chemotherapyCheckpoint inhibitorsII trialAdverse eventsPathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer.
Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Abu-Khalaf M, Sabbath K, Sanft T, Fischbach N, Brandt D, Hofstatter E, DiGiovanna M, Pusztai L. Pathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer. Journal Of Clinical Oncology 2017, 35: 577-577. DOI: 10.1200/jco.2017.35.15_suppl.577.Peer-Reviewed Original ResearchPathologic complete response rateHER2-positive breast cancerDual HER2 blockadeComplete response ratePCR rateEstrogen receptorHER2 blockadeBreast cancerStage IResponse rateGrade 3/4 adverse eventsSymptomatic congestive heart failureClinical stage ICompletion of chemotherapyPhase II studyTaxane-based chemotherapyCongestive heart failureEfficacy of anthracyclinesPositive breast cancerNormal cardiac functionEntire treatment durationER- cancersER cohortNeoadjuvant pertuzumabWeekly paclitaxelDifferences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races.
Szekely B, Safonov A, Karn T, Bhagwagar S, Killelea B, Silber A, Hatzis C, Pusztai L. Differences in the immune microenvironment and genomic characteristics of TNBC in African American women compared to other races. Journal Of Clinical Oncology 2017, 35: e13028-e13028. DOI: 10.1200/jco.2017.35.15_suppl.e13028.Peer-Reviewed Original ResearchTriple-negative breast cancerNon-AA patientsImmune microenvironmentAfrican American womenImmune signaturesNeoantigen loadImmune metagenesLower pathologic complete response (pCR) ratesPathologic complete response rateComplete response rateNegative breast cancerAmerican womenMann-Whitney U testSignificant differencesClonal heterogeneityTCGA data setsDeletion loadNeoadjuvant therapyLymphocyte countTIL countAA patientsOverall mutational loadHistologic tumorsBreast cancerTreatment response
2016
Onset of side effects and adherence to endocrine therapy in the Breast Cancer Endocrine Therapy Adherence (BETA) pilot study.
Epstein L, Jhaveri A, Han G, Abu-Khalaf M, Hofstatter E, Sanft T, DiGiovanna M, Silber A, Adelson K, Chung G, Gross C, Pusztai L, Mougalian S. Onset of side effects and adherence to endocrine therapy in the Breast Cancer Endocrine Therapy Adherence (BETA) pilot study. Journal Of Clinical Oncology 2016, 34: e18136-e18136. DOI: 10.1200/jco.2016.34.15_suppl.e18136.Peer-Reviewed Original Research
2015
Prospective study of the decision-making impact of the Breast Cancer Index in the selection of patients with ER+ breast cancer for extended endocrine therapy.
Sanft T, Aktas B, Schroeder B, Bossuyt V, DiGiovanna M, Abu-Khalaf M, Chung G, Silber A, Hofstatter E, Mougalian S, Epstein L, Hatzis C, Schnabel C, Pusztai L. Prospective study of the decision-making impact of the Breast Cancer Index in the selection of patients with ER+ breast cancer for extended endocrine therapy. Journal Of Clinical Oncology 2015, 33: 538-538. DOI: 10.1200/jco.2015.33.15_suppl.538.Peer-Reviewed Original Research