Evaluation of markers of immunity in different metastatic immune microenvironments suggests more suppression within breast to liver metastases in breast cancer.

PURPOSE: Programmed death receptor ligand-1 (PD-L1) expression and tumor mutational burden (TMB) are approved screening biomarkers for immune checkpoint inhibition (ICI) in advanced triple negative breast cancer. We examined these biomarkers along with characterization of the tumor microenvironment (TME) between breast tumors (BrTs), axillary metastases (AxMs), liver metastases (LvMs), non-axillary lymph node metastases, and non-liver metastases to determine differences related to site of metastatic disease. METHODS: 3076 unpaired biopsies from breast cancer patients were analyzed using whole transcriptome sequencing and NextGen DNA depicting TMB within tumor sites. The PD-L1 positivity was determined with VENTANA PD-L1 (SP142) assay. The immune cell fraction within the TME was calculated by QuantiSeq and MCP-counter. RESULTS: Compared to BrT, more LvM samples had a high TMB (≥ 10 mutations/Mb) and fewer LvM samples had PD-L1+ expression. Evaluation of the TME revealed that LvM sites harbored lower infiltration of adaptive immune cells, such as CD4+, CD8+, and regulatory T-cells compared with the BrT foci. We saw differences in innate immune cell infiltration in LvM compared to BrT, including neutrophils and NK cells. CONCLUSIONS: LvMs are less likely to express PD-L1+ tumor cells but more likely to harbor high TMB as compared to BrTs. Unlike AxMs, LvMs represent a more immunosuppressed TME and demonstrate lower gene expression associated with adaptive immunity compared to BrTs. These findings suggest biopsy site be considered when interpreting results that influence ICI use for treatment and further investigation of immune composition and biomarkers expression by metastatic site.

Changing local therapy in breast cancer: who needs what, and when?

The local therapy of breast cancer continues to evolve toward less surgery. Breast conservation is firmly in place, with recent trends toward decreased rates of re-excision. Axillary dissection is becoming a rare operation and is being replaced by sentinel node biopsy. The switch to sentinel node biopsy occurred first in patients with pathologically tumor-free nodes, and later in patients with limited nodal disease. Sentinel node biopsy is now also widely used in patients with pathologically positive nodes who receive neoadjuvant chemotherapy. Axillary surgery is being replaced with radiotherapy in some situations, and ongoing trials will further clarify the need for nodal radiotherapy in specific situations following neoadjuvant systemic therapy. Shorter radiotherapy regimens are widely accepted as the standard of care following breast conservation, and the omission of radiotherapy is recognized as appropriate for older patients. The appropriate sequencing of specific components of local therapy, particularly with regard to the timing of chemotherapy, requires thoughtful multidisciplinary planning and leveraging of the strengths of each component of therapy. Here, we review issues related to therapeutic sequencing and decision making in the local therapy of breast cancer.

Lower Extremity Arterial Reconstruction in Octogenarians and Older.

BACKGROUND: Despite previous single-institution studies showing that lower extremity arterial reconstruction (LEAR) in octogenarians and older patients may be undertaken with acceptable postoperative morbidity and mortality, there continues to be significant reluctance, in the vascular surgical community, to undertaking these complex revascularization procedures in this very elderly population. We undertook this study in an effort to determine the outcomes of LEAR in octogenarians and older patients on a national level. METHODS: The American College of Surgeons' National Surgical Quality Improvement Program database was queried to identify all patients who underwent LEAR between January 1, 2005 and December 31, 2009. Patient demographics and presenting comorbidities were recorded, and multivariate analyses were performed to compare outcomes in patients 80 and older to those in younger patients. RESULTS: There were 19,028 patients who underwent open infrainguinal LEAR during this time period. Patients ≥80 comprised 18% (3,486 patients), and patients <80 years comprised 82% (15,542 patients). Multivariate analysis demonstrated that patients aged ≥80 years had an increased likelihood of mortality (odds ratio [OR] 1.79; 95% confidence interval [CI] 1.42-2.26), cardiovascular (OR, 1.46; 95% CI, 1.12-1.89), respiratory (OR, 1.37; 95% CI, 1.12-1.67), and renal (OR, 1.57; 95% CI, 1.27-1.95) complications. There was, however, no significant difference in the likelihood of graft failure (OR, 1.04; 95% CI, 0.86-1.27), wound infection (OR, 0.92; 95% CI, 0.79-1.06), or major amputation (OR, 0.59; 95% CI, 0.13-2.74) between these 2 groups. CONCLUSIONS: LEAR in octogenarians is associated with an increased risk of postoperative morbidity and mortality but no increased risk of wound infection, amputation, or graft failure.

Diabetes is not associated with an increased peri-operative mortality or non-infectious morbidity following lower extremity arterial reconstruction.

BACKGROUND: The aim of this study was to determine if, at a national level, diabetes mellitus is associated with worse perioperative outcomes after open lower extremity arterial reconstruction. METHODS: Using Current Procedural Terminology codes, the National Surgical Quality Improvement Program database was queried to identify diabetic and nondiabetic patients who underwent open lower extremity arterial reconstruction from January 1, 2005, to December 31, 2007. These 2 groups were then compared using bivariate and multivariate analyses. RESULTS: There was no difference in mortality between the 2 groups (3.3% in diabetics and 3.5% in nondiabetics, P = .618). On multivariate analysis, there was no difference in the incidence of cardiac, pulmonary, or renal complications between the 2 groups. Diabetics, though, were more likely to develop infectious complications postoperatively. CONCLUSIONS: After lower extremity arterial reconstruction, diabetes is not associated with an increased risk for mortality or an increased rate of major postoperative complications. Diabetics, however, have an increased rate of certain perioperative infections.