Prolonged Tamoxifen treatment augments neutrophil extracellular trap formation in ER+ breast cancer patients 3464

Abstract Description Background Tamoxifen (Tam) is a selective estrogen receptor modifier that is prescribed to patients with estrogen receptor-α (ERα)-positive breast cancer (BC) for up to 10 years. Approximately 30% of the patients treated with long-term Tam experience disease relapse and develop resistance to the therapy. We previously reported that Tam can stimulate neutrophils (NEU) to produce extracellular traps (NETs), and hypothesized that long-term Tam treatment will stimulate NET formation in BC patients which may impact cancer progression. Methods We evaluated the blood samples from Tam treated pre- and postmenopausal ERα+ BC patients. Circulating NEU purified from these samples were processed for NET quantitation, transcriptomic and flow cytometry analysis. Results We found a positive correlation between the level of circulating NETs and Tam duration with significantly higher number NETs in patients on Tam for 5 years or longer. Transcriptomic and flow cytometry analysis revealed that patients treated with Tam for longer duration exhibited differentially modified NEU phenotype that favored NET formation. Conclusion Overall, our results show that long-term Tam treatment correlates with significantly enhanced circulating NETs and modifies NEU phenotype in BC patients. Our ongoing studies are investigating the prognostic and predictive value of Tam-induced NETs and NEU phenotypes in BC metastasis and Tam resistance. Funding Sources Supported by NIH 1R21CA274085 Topic Categories Immune Mechanisms of Human Disease (HUM)