2024
A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features
Klughammer J, Abravanel D, Segerstolpe Å, Blosser T, Goltsev Y, Cui Y, Goodwin D, Sinha A, Ashenberg O, Slyper M, Vigneau S, Jané‐Valbuena J, Alon S, Caraccio C, Chen J, Cohen O, Cullen N, DelloStritto L, Dionne D, Files J, Frangieh A, Helvie K, Hughes M, Inga S, Kanodia A, Lako A, MacKichan C, Mages S, Moriel N, Murray E, Napolitano S, Nguyen K, Nitzan M, Ortiz R, Patel M, Pfaff K, Porter C, Rotem A, Strauss S, Strasser R, Thorner A, Turner M, Wakiro I, Waldman J, Wu J, Gómez Tejeda Zañudo J, Zhang D, Lin N, Tolaney S, Winer E, Boyden E, Chen F, Nolan G, Rodig S, Zhuang X, Rozenblatt-Rosen O, Johnson B, Regev A, Wagle N. A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features. Nature Medicine 2024, 1-14. PMID: 39478111, DOI: 10.1038/s41591-024-03215-z.Peer-Reviewed Original ResearchClinicopathological featuresLocal T cell infiltrationT cell infiltrationMetastatic breast cancerBreast cancer biopsiesCancer-related deathsEpithelial-to-mesenchymal transitionMetastatic diseaseClinically relevant discoveriesTumor biopsiesTumor microenvironmentCancer biopsiesBreast cancerAnatomical sitesMacrophage populationsSingle-nucleus RNA sequencingBiopsyH&E stainingConsecutive serial sectionsClinical annotationTumorSingle-cellSpatial expression characteristicsSerial sectionsCell type composition
2021
Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer
Keenan TE, Li T, Vallius T, Guerriero JL, Tayob N, Kochupurakkal B, Davis J, Pastorello R, Tahara RK, Anderson L, Conway J, He MX, Shannon E, Godin RE, Sorger PK, D'Andrea A, Overmoyer B, Winer EP, Mittendorf EA, Van Allen EM, Shapiro GI, Tolaney SM. Clinical Efficacy and Molecular Response Correlates of the WEE1 Inhibitor Adavosertib Combined with Cisplatin in Patients with Metastatic Triple-Negative Breast Cancer. Clinical Cancer Research 2021, 27: 983-991. PMID: 33257427, PMCID: PMC7887044, DOI: 10.1158/1078-0432.ccr-20-3089.Peer-Reviewed Original ResearchConceptsMetastatic triple-negative breast cancerObjective response rateTriple-negative breast cancerWEE1 inhibitor adavosertibPrior linesClinical benefitBreast cancerMedian progression-free survivalTreatment-related grade 3One-sided type I errorImmune-infiltrated tumorsPhase II studyProgression-free survivalT cell infiltrationImmune gene expressionPrior chemotherapyStable diseaseProtocol therapyII studyPartial responseAdverse eventsMedian ageClinical efficacyGrade 3Tumor biopsies
2020
Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer
Waks AG, Cohen O, Kochupurakkal B, Kim D, Dunn CE, Buendia J, Wander S, Helvie K, Lloyd MR, Marini L, Hughes ME, Freeman SS, Ivy SP, Geradts J, Isakoff S, LoRusso P, Adalsteinsson VA, Tolaney SM, Matulonis U, Krop IE, D’Andrea A, Winer EP, Lin NU, Shapiro GI, Wagle N. Reversion and non-reversion mechanisms of resistance to PARP inhibitor or platinum chemotherapy in BRCA1/2-mutant metastatic breast cancer. Annals Of Oncology 2020, 31: 590-598. PMID: 32245699, PMCID: PMC7946408, DOI: 10.1016/j.annonc.2020.02.008.Peer-Reviewed Original ResearchConceptsMetastatic breast cancerPlatinum chemotherapyDNA-damaging therapyMechanisms of resistanceBreast cancerMetastatic breast cancer patientsBreast cancer patientsTumor DNA sequencingNovel sequence alterationsWhole-exome sequencingDNA-damaging therapiesTreatment failureCancer patientsFunctional statusDisease progressionTumor biopsiesClinical cohortImmunohistochemical stainingSubsequent linesBRCA1/2 mutationsTherapeutic benefitPatientsUseful biomarkerFunctional assessmentTumor sections
2019
Characterization of mutational processes in ER+ metastatic breast cancer.
Buendia-Buendia J, Cohen O, Kim D, Jain E, Winer E, Lin N, Wagle N. Characterization of mutational processes in ER+ metastatic breast cancer. Journal Of Clinical Oncology 2019, 37: 1019-1019. DOI: 10.1200/jco.2019.37.15_suppl.1019.Peer-Reviewed Original ResearchMetastatic breast cancerEarly-stage breast cancerSubset of patientsStage breast cancerWhole-exome sequencingBreast cancerManagement of MBCMutational signaturesMBC samplesMetastatic tumor biopsiesNormal aging processEndocrine therapyMetastatic settingCancer Genome AtlasClinical featuresClinical trialsDisease progressionTumor biopsiesPrimary biopsiesMutational burdenTumor evolutionBreast tumorsMBC tumorsCancerTumor samples
2017
Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors
Adalsteinsson VA, Ha G, Freeman SS, Choudhury AD, Stover DG, Parsons HA, Gydush G, Reed SC, Rotem D, Rhoades J, Loginov D, Livitz D, Rosebrock D, Leshchiner I, Kim J, Stewart C, Rosenberg M, Francis JM, Zhang CZ, Cohen O, Oh C, Ding H, Polak P, Lloyd M, Mahmud S, Helvie K, Merrill MS, Santiago RA, O’Connor E, Jeong SH, Leeson R, Barry RM, Kramkowski JF, Zhang Z, Polacek L, Lohr JG, Schleicher M, Lipscomb E, Saltzman A, Oliver NM, Marini L, Waks AG, Harshman LC, Tolaney SM, Van Allen EM, Winer EP, Lin NU, Nakabayashi M, Taplin ME, Johannessen CM, Garraway LA, Golub TR, Boehm JS, Wagle N, Getz G, Love JC, Meyerson M. Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors. Nature Communications 2017, 8: 1324. PMID: 29109393, PMCID: PMC5673918, DOI: 10.1038/s41467-017-00965-y.Peer-Reviewed Original ResearchConceptsWhole-exome sequencingCell-free DNATumor biopsiesTumor whole-exome sequencingTumor contentHigh concordanceClonal somatic mutationsMetastatic tumorsBreast cancerMetastatic prostateBlood samplesPatientsTumor mutationsCfDNA profilingBiopsyMutational signaturesSomatic mutationsTumorsNumber alterationsConcordanceComprehensive profilingNeoantigensSequencingProstateCancer
2016
The Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research.
Wagle N, Painter C, Krevalin M, Oh C, Anderka K, Larkin K, Lennon N, Dillon D, Frank E, Winer E, Lander E, Golub T. The Metastatic Breast Cancer Project: A national direct-to-patient initiative to accelerate genomics research. Journal Of Clinical Oncology 2016, 34: lba1519-lba1519. DOI: 10.1200/jco.2016.34.18_suppl.lba1519.Peer-Reviewed Original ResearchMetastatic breast cancerBreast Cancer ProjectMedical recordsMedian timeBreast cancerDe novo metastatic breast cancerMedical providersCancer ProjectNovo metastatic breast cancerMedian ageInitial diagnosisTumor biopsiesMost tumorsSaliva kitsClinical informationNationwide studyExtraordinary responsePatient approachCommunity settingsTumorsPatient initiativeSaliva samplesTherapyGermline DNACancer
2012
SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC).
Mayer I, Abramson V, Balko J, Isakoff S, Kuba M, Sanders M, Forero-Torres A, Yap J, Van Den Abbeele A, Li Y, Arteaga C, Winer E. SU2C phase Ib study of pan-PI3K inhibitor BKM120 with letrozole in ER+/HER2- metastatic breast cancer (MBC). Journal Of Clinical Oncology 2012, 30: 510-510. DOI: 10.1200/jco.2012.30.15_suppl.510.Peer-Reviewed Original ResearchMetastatic breast cancerPan-PI3K inhibitor BKM120FDG-PETArm API3K pathway alterationsPhase Ib studyPhase Ib trialPost-menopausal patientsPI3K pathway inhibitionPI3K mutationsPI3K inhibitorsIb trialStable diseaseVisceral metastasesUnacceptable toxicityMost patientsArm BMedian ageDisease progressionPharmacodynamic biomarkersBreast cancerTreatment responseTumor biopsiesAntiestrogen resistanceIb study