Tumor immune microenvironment of self-identified African American and non-African American triple negative breast cancer.

Differences in the tumor immune microenvironment may result in differences in prognosis and response to treatment in cancer patients. We hypothesized that differences in the tumor immune microenvironment may exist between African American (AA) and NonAA patients, due to ancestry-related or socioeconomic factors, that may partially explain differences in clinical outcomes. We analyzed clinically matched triple-negative breast cancer (TNBC) tissues from self-identified AA and NonAA patients and found that stromal TILs, PD-L1 IHC-positivity, mRNA expression of immune-related pathways, and immunotherapy response predictive signatures were significantly higher in AA samples (p < 0.

Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.

Purpose: In metastatic triple-negative breast cancer (mTNBC), consistent biomarkers of immune checkpoint inhibitor (ICI) therapy benefit remain elusive. We evaluated the immune, genomic, and transcriptomic landscape of mTNBC in patients treated with ICIs.

Methods: We identified 29 patients with mTNBC treated with pembrolizumab or atezolizumab, either alone (n = 9) or in combination with chemotherapy (n = 14) or targeted therapy (n = 6), who had tumor tissue and/or blood available before ICI therapy for whole-exome sequencing.

Comprehensive Analysis of Metabolic Isozyme Targets in Cancer.

Unlabelled: Metabolic reprogramming is a hallmark of malignant transformation, and loss of isozyme diversity (LID) contributes to this process. Isozymes are distinct proteins that catalyze the same enzymatic reaction but can have different kinetic characteristics, subcellular localization, and tissue specificity. Cancer-dominant isozymes that catalyze rate-limiting reactions in critical metabolic processes represent potential therapeutic targets.

Evidence of accelerated epigenetic aging of breast tissues in patients with breast cancer is driven by CpGs associated with polycomb-related genes.

Purpose: Age is one of the strongest risk factors for the development of breast cancer, however, the underlying etiology linking age and breast cancer remains unclear. We have previously observed links between epigenetic aging signatures in breast/tumor tissue and breast cancer risk/prevalence. However, these DNA methylation-based aging biomarkers capture diverse epigenetic phenomena and it is not known to what degree they relate to breast cancer risk, and/or progression.

Quantitative assessment of the immune microenvironment in African American Triple Negative Breast Cancer: a case-control study.

Purpose: Triple negative breast cancer (TNBC) is more common in African American (AA) than Non-AA (NAA) population. We hypothesize that tumor microenvironment (TME) contributes to this disparity. Here, we use multiplex quantitative immunofluorescence to characterize the expression of immunologic biomarkers in the TME in both populations.

Tumor mutational burden as a predictor of immunotherapy response in breast cancer.

Tumor mutational burden (TMB) is a promising tool to help define patients with triple-negative breast cancer (TNBC) most likely to benefit from immune checkpoint blockade (ICB) therapies. Roughly reflecting the degree of neo-antigens that tumors present to immune cells, TMB associates with multiple measures of tumoral immunogenicity and has proven clinically useful in cancers with relatively high mutation burden. TNBC carries higher TMB than other breast cancer subtypes, and recent data suggest that high-TMB TNBC cases may derive particular benefit from ICB in combination with chemotherapy (GeparNuevo, IMpassion130) or even ICB alone (KEYNOTE-119, TAPUR).

Immunological Differences Between Immune-Rich Estrogen Receptor-Positive and Immune-Rich Triple-Negative Breast Cancers.

Purpose: A subset of estrogen receptor-positive (ER-positive) breast cancer (BC) contains high levels of tumor-infiltrating lymphocytes (TILs), similar to triple-negative BC (TNBC). The majority of immuno-oncology trials target TNBCs because of the greater proportion of TIL-rich TNBCs. The extent to which the immune microenvironments of immune-rich ER-positive BC and TNBC differ is unknown.

Germline variant burden in cancer genes correlates with age at diagnosis and somatic mutation burden.

Cancers harbor many somatic mutations and germline variants, we hypothesized that the combined effect of germline variants that alter the structure, expression, or function of protein-coding regions of cancer-biology related genes (gHFI) determines which and how many somatic mutations (sM) must occur for malignant transformation. We show that gHFI and sM affect overlapping genes and the average number of gHFI in cancer hallmark genes is higher in patients who develop cancer at a younger age (r = -0.77, P = 0.

Utilization and Outcomes of Local Anesthesia and Peripheral Nerve Block for Hybrid Lower Extremity Revascularization.

To investigate the utilization of local anesthesia or peripheral nerve block with monitored anesthesia care (LPMAC) and its impact on the perioperative outcomes of hybrid lower extremity revascularization (LER) compared with general anesthesia (GA). A search of the ACS-NSQIP database between 2005 and 2017 identified 9430 patients who underwent hybrid LER for peripheral artery disease. Excluding 449 ineligible cases left 8981 hybrid LER patients for analysis.

Use of neuraxial anesthesia for hybrid lower extremity revascularization is associated with reduced perioperative morbidity.

Objective: Recent advances in endovascular technology have allowed complex peripheral arterial disease (PAD) to be treated with less invasive hybrid procedures under neuraxial anesthesia. This study investigates the perioperative outcomes of hybrid lower extremity revascularization (LER) performed under neuraxial anesthesia (NAA) vs general anesthesia (GA). We hypothesize that the use of NAA is associated with improved outcomes.

Immune microenvironment of triple-negative breast cancer in African-American and Caucasian women.

Purpose: African-American (AA) patients with triple-negative breast cancer (TNBC) are less likely to achieve pathologic complete response from neoadjuvant chemotherapy and have poorer prognosis than Caucasian patients with TNBC, suggesting potential biological differences by race. Immune infiltration is the most consistent predictive marker for chemotherapy response and improved prognosis in TNBC. In this study, we test the hypothesis that the immune microenvironment differs between AA and Caucasian patients.

Incorporating Genomics Into the Care of Patients With Advanced Breast Cancer.

Metastatic breast cancer is a very heterogeneous disease. Recent advances in genomic sequencing have revealed genetic diversity between patients and across distinct subclonal cell populations within the same patient that may evolve across metastatic tumor sites and during treatment. With the increasing availability of commercial and laboratory-developed tests that can detect genomic alterations from patient tumor and blood samples, translating this knowledge into improved clinical care remains a challenge.

Characterizing the immune microenvironment in high-risk ductal carcinoma in situ of the breast.

Purpose: The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence.