Identification of CD105+ Extracellular Vesicles as a Candidate Biomarker for Metastatic Breast Cancer.

BACKGROUND: Extracellular vehicles (EVs) released by malignant tumor cells can mediate the immune response and promote metastasis through intercellular communication. EV analysis is an emerging cancer surveillance tool with advantages over traditional liquid biopsy methods. The aim of this pilot study is to identify actionable EV signatures in metastatic breast cancer. MATERIALS AND METHODS: Under an IRB-approved protocol for the analysis of patient plasma, samples were collected from women with newly diagnosed or progressive metastatic breast cancer and from women without cancer. Enriched EVs were analyzed via a bead-based multiplex assay designed to detect 37 distinct tumor-relevant epitopes. The mean fluorescent intensity of EV epitopes meeting a minimum threshold of detectability was compared between groups via independent samples t-test. Subgroup analysis was conducted for metastatic breast cancer patients who were positive for estrogen and/or progesterone receptors and negative for HER2. Other variables potentially affecting CD105 levels were also analyzed. RESULTS: CD105 was found to have a significantly higher mean fluorescent intensity in participants with metastatic breast cancer compared to control participants (P = 0.04). ER/PR+ subgroup analysis revealed a similar pattern compared to control participants (P = 0.01). Other analyzed variables were not found to have a significant correlation with CD105 levels. CONCLUSIONS: CD105 EV levels were significantly higher in samples from participants with breast cancer compared to controls. Given that CD105 is known to mediate angiogenesis and promote metastasis, EV-associated CD105 in plasma represents a potential biomarker for diagnosis, surveillance and therapeutic targeting in patients with metastatic breast cancer.

National Cancer Database trends in surgical resection of the breast primary for stage IV breast cancer.

BACKGROUND: Survival benefit after resection of the breast primary for women with metastatic breast cancer reported in retrospective studies has not been uniformly confirmed by randomized controlled trials. To assess the need for dissemination of trial results by the ACS Cancer Research Program Dissemination and Implementation (ACS CRP D&I) committee, we analyzed trends and predictors of surgery and other therapies for stage IV breast cancer. METHODS: The National Cancer Database (NCDB) was queried to identify women diagnosed with clinical stage IV breast cancer of ductal, lobular, or metaplastic histology between 2004 and 2017. Trends in utilization of breast surgery and other treatments and possible predictors of breast surgery were examined in univariable and multivariable analyses. RESULTS: We identified 87,331 cases meeting inclusion criteria. Rates of surgical resection rose until 2009, peaking at 37%, then declined to a rate of 18% in 2017. The largest decline was seen in the hormone receptor positive (HR+), HER2 negative (HER2-) subgroup with up to 70% of patients undergoing surgery in 2007, down to 15% in 2017. In 2004, the rate of systemic therapy alone was slightly more common than locoregional therapy (surgery and/or radiation) with or without systemic therapy (48% vs 37%). However, by 2017, systemic therapy alone was by far more common (69% vs 20%). CONCLUSION: Rates of surgical resection of the breast primary for stage IV breast cancer have been on the decline in recent years, suggesting that providers at Commission on Cancer accredited hospitals are becoming more selective about who will be offered surgical resection.