2023
Tucatinib 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
2021
How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer?
Chagpar A, Lannin D, Mougalian S, Berger E, Gross C, Horowitz N, Sanft T, DiGiovanna M, Golshan M, Pusztai L. How did the COVID crisis affect use of neoadjuvant therapy for patients with breast cancer? Journal Of Clinical Oncology 2021, 39: e18708-e18708. DOI: 10.1200/jco.2021.39.15_suppl.e18708.Peer-Reviewed Original ResearchUse of NTNeoadjuvant therapyEarly pandemic periodBreast cancerNon-metastatic breast cancerPractice settingsEarly pandemicFlatiron Health databaseNeoadjuvant endocrine therapyTechnology-enabled abstractionSame period one yearSimilar clinicopathologic featuresLongitudinal electronic health recordsPeriod one yearElectronic health recordsTNBC subsetEndocrine therapyPatient ageTN patientsClinicopathologic featuresContemporary cohortClinical stageCancer clinicCancer managementHigh riskAdjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE
Mamounas EP, Untch M, Mano MS, Huang C, Geyer CE, von Minckwitz G, Wolmark N, Pivot X, Kuemmel S, DiGiovanna MP, Kaufman B, Kunz G, Conlin AK, Alcedo JC, Kuehn T, Wapnir I, Fontana A, Hackmann J, Polikoff J, Saghatchian M, Brufsky A, Yang Y, Zimovjanova M, Boulet T, Liu H, Tesarowski D, Lam LH, Song C, Smitt M, Loibl S. Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE. Annals Of Oncology 2021, 32: 1005-1014. PMID: 33932503, DOI: 10.1016/j.annonc.2021.04.011.Peer-Reviewed Original ResearchConceptsInvasive disease-free survivalAdjuvant T-DM1Residual invasive diseaseT-DM1 armNeoadjuvant chemotherapyEarly breast cancerHigh-risk tumorsRisk of recurrenceT-DM1Central nervous systemPeripheral neuropathyCNS recurrenceInvasive diseaseBreast cancerHER2-positive eBC patientsInvasive early breast cancerAnthracycline-based neoadjuvant chemotherapyHuman epidermal growth factor receptor 2HER2-positive breast cancerEpidermal growth factor receptor 2Overall riskAdjuvant trastuzumab emtansineBaseline peripheral neuropathyLonger PN durationMore grade 3
2020
Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer
Kunst N, Wang SY, Hood A, Mougalian SS, DiGiovanna MP, Adelson K, Pusztai L. Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies for Women With ERBB2 (HER2)–Positive Breast Cancer. JAMA Network Open 2020, 3: e2027074. PMID: 33226431, PMCID: PMC7684449, DOI: 10.1001/jamanetworkopen.2020.27074.Peer-Reviewed Original ResearchMeSH KeywordsAdo-Trastuzumab EmtansineAdultAgedAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, ImmunologicalAntineoplastic Agents, PhytogenicBreast NeoplasmsCase-Control StudiesCost-Benefit AnalysisCross-Linking ReagentsDrug Therapy, CombinationFemaleHumansImmunosuppressive AgentsMiddle AgedNeoadjuvant TherapyPaclitaxelQuality-Adjusted Life YearsReceptor, ErbB-2TrastuzumabTubulin ModulatorsUnited StatesConceptsErbB2-positive breast cancerAdjuvant treatment strategiesAdjuvant T-DM1Pathologic complete responseT-DM1Treatment strategiesBreast cancerKATHERINE trialResidual diseaseNeoadjuvant regimenHigher health benefitsHealth care payer perspectiveAdjuvant trastuzumab emtansineAnthracycline/cyclophosphamideDifferent adjuvant therapiesFlatiron Health databaseIncremental cost-effectiveness ratioNeoadjuvant treatment optionsHealth benefitsPositive breast cancerCare payer perspectiveCost-effectiveness ratioBase-case analysisDecision analytic modelH. Patients53. TUCATINIB VS PLACEBO ADDED TO TRASTUZUMAB AND CAPECITABINE FOR PATIENTS WITH PREVIOUSLY TREATED HER2+ METASTATIC BREAST CANCER (MBC) WITH BRAIN METASTASES (BM) (HER2CLIMB)
Lin N, Murthy R, Anders C, Borges V, Hurvitz S, Loi S, Abramson V, Bedard P, Oliveira M, Zelnack A, DiGiovanna M, Bachelot T, Chien A, O’Regan R, Wardley A, Mueller V, Carey L, McGoldrick S, An X, Winer E. 53. TUCATINIB VS PLACEBO ADDED TO TRASTUZUMAB AND CAPECITABINE FOR PATIENTS WITH PREVIOUSLY TREATED HER2+ METASTATIC BREAST CANCER (MBC) WITH BRAIN METASTASES (BM) (HER2CLIMB). Neuro-Oncology Advances 2020, 2: ii11-ii11. PMCID: PMC7401403, DOI: 10.1093/noajnl/vdaa073.041.Peer-Reviewed Original ResearchMetastatic breast cancerBrain metastasesCNS-PFSSecond progressionControl armEfficacy analysisBrain progressionExploratory efficacy analysesMedian CNS-PFSBaseline brain MRIMedian OSOverall deathRECIST 1.1Study therapyMedian timeInvestigator's evaluationIC diseaseLocal treatmentBreast cancerBrain MRIReduced riskCapecitabineTrastuzumabTucatinibHER2Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB).
Lin N, Murthy R, Anders C, Borges V, Hurvitz S, Loi S, Abramson V, Bedard P, Oliveira M, Zelnak A, DiGiovanna M, Bachelot T, Chien A, O'Regan R, Wardley A, Müller V, Carey L, McGoldrick S, An G, Winer E. Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB). Journal Of Clinical Oncology 2020, 38: 1005-1005. DOI: 10.1200/jco.2020.38.15_suppl.1005.Peer-Reviewed Original ResearchMetastatic breast cancerProgression-free survivalObjective response rateBrain metastasesOverall survivalCNS-PFSControl armSecond progressionEfficacy analysisBrain progressionLocal treatmentBreast cancerProlongation of PFSMedian progression-free survivalExploratory efficacy analysesMedian CNS-PFSMedian overall survivalBaseline brain MRIHER2 kinase inhibitorDeath overallRECIST 1.1Study therapyFree survivalInvestigator's evaluationIC disease
2018
Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC).
Pusztai L, Hofstatter E, Chung G, Horowitz N, Lannin D, Killelea B, Chagpar A, DiGiovanna M, Frederick C, Burello T, Harigopal M. Durvalumab (MEDI4736) concurrent with nab-paclitaxel and dose dense doxorubicin cyclophosphamide (ddAC) as neoadjuvant therapy for triple negative breast cancer (TNBC). Journal Of Clinical Oncology 2018, 36: 586-586. DOI: 10.1200/jco.2018.36.15_suppl.586.Peer-Reviewed Original Research
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 paclitaxel
2015
Review of trends in adjuvant chemotherapy regimens in breast cancer over 10 year period at Yale New Haven Hospital (YNHH).
Gnanajothy R, Chung G, DiGiovanna M, Abu-Khalaf M, Lannin D, Harris L. Review of trends in adjuvant chemotherapy regimens in breast cancer over 10 year period at Yale New Haven Hospital (YNHH). Journal Of Clinical Oncology 2015, 33: 144-144. DOI: 10.1200/jco.2015.33.28_suppl.144.Peer-Reviewed Original ResearchProspective 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
2013
Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer.
James E, Chung G, Sowers N, Clark M, Lilian R, Abraham G, Chmael S, Cappiello M, DiGiovanna M, Hofstatter E, Sanft T, Israel G, Pusztai L, Harris L, Abu-Khalaf M. Phase I study of the HDAC inhibitor vorinostat in combination with capecitabine in a biweekly schedule in advanced breast cancer. Journal Of Clinical Oncology 2013, 31: 154-154. DOI: 10.1200/jco.2013.31.26_suppl.154.Peer-Reviewed Original ResearchDose-expansion phaseGrade 3 non-hematological toxicityGrade 4 febrile neutropeniaCycle-1 DLTGrade 3 fatigueGrade 3/4 toxicitiesGrade 4 neutropeniaGrade 4 thrombocytopeniaMedian age 51Non-hematological toxicitiesObjective response rateAdvanced breast cancerDose-escalation phaseModest clinical activityHDAC inhibitor vorinostatClinical trial informationHistone deacetylase inhibitorsFebrile neutropeniaStable diseaseObjective responsePrior linesHematological toxicityTreatment delayClinical activityBreast cancerMulticenter phase II trial of neoadjuvant carboplatin, weekly nab-paclitaxel, and trastuzumab in stage II-III HER2+ breast cancer: A BrUOG study.
Sinclair N, Sakr B, Abu-Khalaf M, Somlo G, Black R, Chung G, Rizack T, Strenger R, Fenton M, DiGiovanna M, Constantinou M, Lannin D, Legare R, Chagpar A, Sambandam S, Bossuyt V, Rosati K, Harris L, Sikov W. Multicenter phase II trial of neoadjuvant carboplatin, weekly nab-paclitaxel, and trastuzumab in stage II-III HER2+ breast cancer: A BrUOG study. Journal Of Clinical Oncology 2013, 31: 619-619. DOI: 10.1200/jco.2013.31.15_suppl.619.Peer-Reviewed Original ResearchPathologic complete responseResidual cancer burdenNeoadjuvant chemotherapyT regimenNab-paclitaxelBreast cancerMulticenter phase II trialHuman epidermal growth factor receptor 2Epidermal growth factor receptor 2Median age 51Weekly nab-paclitaxelPhase II trialGrowth factor receptor 2Factor receptor 2Adjuvant chemotherapyFebrile neutropeniaNeoadjuvant carboplatinAdjuvant treatmentII trialDose intensityExcellent prognosisPathologic responseResearch biopsiesComplete responseResidual tumor
2012
Neoadjuvant weekly nab-paclitaxel (wA), carboplatin (Cb) plus bevacizumab (B) with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus B in ER+/HER2-negative (HR+) and triple-negative (TN) breast cancer (BrCa): A BrUOG study.
Sinclair N, Abu-Khalaf M, Rizack T, Rosati K, Chung G, Legare R, DiGiovanna M, Fenton M, Bossuyt V, Strenger R, Sakr B, Lannin D, Gass J, Harris L, Sikov W. Neoadjuvant weekly nab-paclitaxel (wA), carboplatin (Cb) plus bevacizumab (B) with or without dose-dense doxorubicin-cyclophosphamide (ddAC) plus B in ER+/HER2-negative (HR+) and triple-negative (TN) breast cancer (BrCa): A BrUOG study. Journal Of Clinical Oncology 2012, 30: 1045-1045. DOI: 10.1200/jco.2012.30.15_suppl.1045.Peer-Reviewed Original ResearchResidual cancer burdenCR/PRTriple-negative breast cancerAnthracycline-based therapyWeekly nab-paclitaxelSerious adverse eventsLonger treatment durationAUC 6Doxorubicin-cyclophosphamideInvasive BRCANeutropenic feverNSABP BWeekly paclitaxelGI bleedNab-paclitaxelAdverse eventsAxillary nodesPartial responseSystemic therapyCancer burdenCohort 2Cohort 1Breast cancerGrade 3BRCA patients
2011
A phase I study of biweekly capecitabine and the histone deacetylase inhibitors (HDACi) vorinostat in for advanced breast cancer (BC).
Abu-Khalaf M, Kim T, Chung G, DiGiovanna M, Radke S, Cornfeld D, Harris L. A phase I study of biweekly capecitabine and the histone deacetylase inhibitors (HDACi) vorinostat in for advanced breast cancer (BC). Journal Of Clinical Oncology 2011, 29: e13609-e13609. DOI: 10.1200/jco.2011.29.15_suppl.e13609.Peer-Reviewed Original Research
2009
Histologic subtypes of ductal intraepithelial neoplasia (DIN) of the breast: Characteristic associations and biology
Schwartz J, Christy C, Grube B, Rishi M, Tavassoli F, Bossuyt V, Harris L, DiGiovanna M, Lannin D. Histologic subtypes of ductal intraepithelial neoplasia (DIN) of the breast: Characteristic associations and biology. Journal Of Clinical Oncology 2009, 27: 633-633. DOI: 10.1200/jco.2009.27.15_suppl.633.Peer-Reviewed Original ResearchDuctal intraepithelial neoplasiaHistologic subtypeInvasive cancerHormone receptor negativePure invasive cancersInvasive breast cancerDifferent clinical behaviorDifferent histologic subtypesCribriform subtypeMicropapillary subtypeReceptor negativeIntraepithelial neoplasiaComedo subtypeClinical behaviorPapillary subtypeBreast centerBreast cancerLarge lesionsSubtypesCancerBiologic significanceHormone receptorsHistologic architectureBiological behaviorSignificant financial relationshipAssociation between HER2/neu overexpression and calcifications in breast cancer
Christy C, Rishi M, Schwartz J, Grube B, Bossuyt V, Philpotts L, DiGiovanna M, Tavassoli F, Lannin D. Association between HER2/neu overexpression and calcifications in breast cancer. Journal Of Clinical Oncology 2009, 27: 579-579. DOI: 10.1200/jco.2009.27.15_suppl.579.Peer-Reviewed Original ResearchNeu overexpressionBreast cancerReceptor negativityInvasive tumorsNeu positivityMammographic calcificationsHER2/neu overexpressionHormone receptor negativityProgesterone receptor negativityHormone receptor statusInvasive breast cancerMultivariate logistic regressionPresence of necrosisImportant tumor markerHistologic calcificationLymphovascular invasionNodal statusReceptor statusRetrospective reviewTumor sizeInvasive cancerHistologic characteristicsTumor gradeClinical usefulnessHistologic examination
2006
Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC)
Abu-Khalaf M, Kim R, Cohenuram M, Chung G, Digiovanna M, Haffty B, Carter D, Horvath L, Tavassoli F, Burtness B. Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC). Journal Of Clinical Oncology 2006, 24: 10721-10721. DOI: 10.1200/jco.2006.24.18_suppl.10721.Peer-Reviewed Original ResearchPathologic complete response rateStage III breast cancerDisease-free survivalBreast cancerOverall survivalResponse rateImproved disease-free survivalAddition of taxanesComplete response rateGrade 4 neutropeniaPathologic response rateAcute renal failureAdvanced breast cancerAdjuvant CMFAdjuvant settingDD chemotherapyDose CNeutropenic feverEligible patientsNeoadjuvant settingPrimary endpointRenal failureEjection fractionMedian ageTreatment cessation