A Prospective, Multicenter Registry Study to Evaluate the Clinical Feasibility of Targeted Axillary Dissection (TAD) in Node-positive Breast Cancer Patients.

OBJECTIVE: This study aimed to investigate the feasibility and accuracy of non-radioactive TLN biopsy and TAD in routine clinical practice. BACKGROUND DATA: TAD involves TLN biopsy (TLNB) and sentinel lymph node biopsy and was recently introduced as a new standard for less invasive axillary staging in BC patients undergoing neoadjuvant systemic therapy (NST); however, clinical evidence is limited. METHODS: The SenTa study is a prospective registry study conducted at 50 centers. Patients with invasive BC who nderwent clip insertion into the most suspicious axillary lymph node were eligible. Axillary surgery was performed with or without sentinel lymph node biopsy, TLNB, and/or axillary lymph node dissection (ALND). Main endpoints were the detection rate and FNR of TLNB and TAD after NST. RESULTS: Between 2017 and 2018, 548 consecutive BC patients underwent clip placement into biopsy-confirmed positive lymph nodes. After NST (n = 473), the clipped TLN was intraoperatively resected in 329 of 423 patients [77.8%, 95% confidence interval (CI): 74.0-82.0]. TAD was successful in 199 of 229 patients (detection rate: 86.9%, 95% CI: 81.8-91.0), the SLN and TLN were identical in 129 patient (64.8%). FNRs were 7.2% (8 of 111, 95% CI: 3.1-13.6) for TLNB followed by ALND (n = 203) and 4.3% (2 of 46, 95% CI: 0.5-14.8) for TAD followed by ALND (n = 77). CONCLUSIONS: The SenTa study demonstrates the feasibility of TAD in a real-world cohort of BC patients. Our findings are of great importance for de-escalation of surgical strategies.

Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice.

Activation of hepatic stellate cells in response to chronic inflammation represents a crucial step in the development of liver fibrosis. However, the molecules involved in the interaction between immune cells and stellate cells remain obscure. Herein, we identify the chemokine CCL5 (also known as RANTES), which is induced in murine and human liver after injury, as a central mediator of this interaction. First, we showed in patients with liver fibrosis that CCL5 haplotypes and intrahepatic CCL5 mRNA expression were associated with severe liver fibrosis. Consistent with this, we detected Ccl5 mRNA and CCL5 protein in 2 mouse models of liver fibrosis, induced by either injection of carbon tetrachloride (CCl4) or feeding on a methionine and choline-deficient (MCD) diet. In these models, Ccl5-/- mice exhibited decreased hepatic fibrosis, with reduced stellate cell activation and immune cell infiltration. Transplantation of Ccl5-deficient bone marrow into WT recipients attenuated liver fibrosis, identifying infiltrating hematopoietic cells as the main source of Ccl5. We then showed that treatment with the CCL5 receptor antagonist Met-CCL5 inhibited cultured stellate cell migration, proliferation, and chemokine and collagen secretion. Importantly, in vivo administration of Met-CCL5 greatly ameliorated liver fibrosis in mice and was able to accelerate fibrosis regression. Our results define a successful therapeutic approach to reduce experimental liver fibrosis by antagonizing Ccl5 receptors.