Optimal timing and dosing of adjuvant cyclin-dependent kinase (CDK) 4/6 inhibitor in early breast cancer is controversial. This prospective phase II clinical trial investigated tolerability and safety of two ribociclib dosing schedules. Patients with stage I-III hormone receptor-positive (HR+)/HER2- breast cancer on adjuvant endocrine therapy (ET) were randomized to two ribociclib dosing schedules: 400 mg continuous vs 600 mg intermittent, with initiation in early (prior ET < 2 years) vs delayed (prior ET ≥ 2 years) setting.
View Article and Find Full Text PDFCirculating Tumor Cells (CTCs) in blood encompass DNA, RNA, and protein biomarkers, but clinical utility is limited by their rarity. To enable tumor epitope-agnostic interrogation of large blood volumes, we developed a high-throughput microfluidic device, depleting hematopoietic cells through high-flow channels and force-amplifying magnetic lenses. Here, we apply this technology to analyze patient-derived leukapheresis products, interrogating a mean blood volume of 5.
View Article and Find Full Text PDFPurpose: Antibody-drug conjugates (ADCs) harboring topoisomerase I (TOP1) inhibitor payloads have improved survival for patients with metastatic breast cancer (MBC). However, knowledge of ADC resistance mechanisms and potential impact on sequential use of ADCs is limited. Here, we report the incidence and characterization of TOP1 mutations arising in the setting of ADC resistance in MBC.
View Article and Find Full Text PDFImmune exclusion inhibits anti-tumor immunity and response to immunotherapy, but its mechanisms remain poorly defined. Here, we demonstrate that Trophoblast Cell-Surface Antigen 2 (TROP2), a key target of emerging anti-cancer Antibody Drug Conjugates (ADCs), controls barrier-mediated immune exclusion in Triple-Negative Breast Cancer (TNBC) through Claudin 7 association and tight junction regulation. TROP2 expression is inversely correlated with T cell infiltration and strongly associated with outcomes in TNBC.
View Article and Find Full Text PDFAdditional therapies are needed to improve outcomes in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Research on the potential role of immunotherapy, particularly programmed cell death protein 1/programmed cell death ligand 1 inhibitors, is rapidly expanding in both the early and metastatic settings with some preliminary evidence suggesting benefit when used as part of combination therapy. Several ongoing phase 3 studies should help define their future role in treating these patients.
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