Neutrophil Biomarkers Can Predict Cardiotoxicity of Anthracyclines in Breast Cancer.

Doxorubicin (DOX), a commonly used anticancer agent, causes cardiotoxicity that begins with the first dose and may progress to heart failure years after treatment. An inflammatory response associated with neutrophil recruitment has been recognized as a mechanism of DOX-induced cardiotoxicity. This study aimed to validate mRNA expression of the previously identified biomarkers of DOX-induced cardiotoxicity, PGLYRP1, CAMP, MMP9, and CEACAM8, and to assay their protein expression in the peripheral blood of breast cancer patients.

ASCO Domestic Quality Programs.

A growing sense of the need to define good-quality cancer care has emerged in the past decade of the 20th century. The goals were to assess, improve, and reward quality. Animated debates between cancer care delivery academic and community organizations, governmental agencies, and insurance companies have led to multiple initiatives and pilot projects.

Exosomal MicroRNA and Protein Profiles of Hepatitis B Virus-Related Hepatocellular Carcinoma Cells.

Infection with hepatitis B virus (HBV) is a main risk factor for hepatocellular carcinoma (HCC). Extracellular vesicles, such as exosomes, play an important role in tumor development and metastasis, including regulation of HBV-related HCC. In this study, we have characterized exosome microRNA and proteins released in vitro from hepatitis B virus (HBV)-related HCC cell lines SNU-423 and SNU-182 and immortalized normal hepatocyte cell lines (THLE2 and THLE3) using microRNA sequencing and mass spectrometry.

Associations of Early Completion of Advance Directives With Key End-of-Life Quality Measures: Analysis of an ASCO Quality Oncology Practice Initiative Patient Cohort.

Purpose: Despite the growing calls for early and ubiquitous completion of advance directives (ADs), studies exploring links between AD completion and their impact on outcomes of patients with cancer have mixed conclusions. We used the ASCO Quality Oncology Practice Initiative (QOPI) registry to compare end-of-life (EOL) quality measures and the effect of QOPI certification among patients with and without early AD completion, defined as completion within the first three oncology visits after cancer diagnosis.

Methods: Deidentified patient-level data were analyzed from the QOPI database from 2015 through 2017.

Clinical Impact of ASCO Choosing Wisely Guidelines on Staging Imaging for Early-Stage Breast Cancers: A Time Series Analysis Using SEER-Medicare Data.

Purpose: American Society for Clinical Oncology released the Choosing Wisely list in 2012, highlighting low-value procedures that lack evidence, advising against the use of positron emission tomography, computerized tomography, and radionuclide bone scans for the staging of early-stage breast cancer at low risk for metastasis. The objective of the study was to assess the impact of the American Society of Clinical Oncology Choosing Wisely guidelines on inappropriate staging imaging among early-stage breast cancers.

Methods: The Surveillance, Epidemiology, and End Results Program-Medicare data set was used to identify 50,004 women age 66 years and older with new incident diagnosis of early-stage breast cancer (stage 0 through stage 2a; T < 4, N = 0, and M = 0).

Harnessing Antibody Polyspecificity for Cancer Immunotherapy.

Targeting the diverse glycan repertoire expressed on tumor cells is considered a viable therapeutic strategy to deal with tumor cell heterogeneity. Inherently polyspecific, natural, glycan-reactive antibodies are purported to be protective in thwarting infections and in cancer immunotherapy. Tumor-associated carbohydrate antigens (TACAs) are related to pathogen glycans, to which nascent or natural antibodies exist and IgM responses are elicited.

Hematology/Oncology Fellowship Programs' Participation in the Quality Oncology Practice Initiative.

Purpose: In the first decade of this millennium, ASCO pioneered a quality measurement tool, the Quality Oncology Practice Initiative (QOPI). Despite an Accreditation Council for Graduate Medical Education (ACGME) requirement since 2012 for oncology fellows to participate in quality improvement (QI) projects, the uptake of QOPI remains modest.

Methods: This study examined reasons for low QOPI participation by surveying participating and nonparticipating HemOnc Fellowship Programs.

Pre-Treatment Staging Imaging in Rectal Cancer: Results From the Quality Oncology Practice Initiative.

Purpose: For patients with nonmetastatic rectal cancer, the National Comprehensive Cancer Network guidelines recommend initial staging using pelvic magnetic resonance imaging or endorectal ultrasound to determine the stage of the disease before initial therapy or surgery. This imaging workup helps determine the T and N staging, which is essential to determine optimal treatment for a patient. The current study examined practice concordance with this guideline using a quality measure in ASCO's Quality Oncology Practice Initiative (QOPI) that specifically addressed staging workup for patients with rectal cancer.

Circulating Exosomal microRNAs as Predictive Biomarkers of Neoadjuvant Chemotherapy Response in Breast Cancer.

Background: Neoadjuvant chemotherapy (NACT) is an increasingly used approach for treatment of breast cancer. The pathological complete response (pCR) is considered a good predictor of disease-specific survival. This study investigated whether circulating exosomal microRNAs could predict pCR in breast cancer patients treated with NACT.

Use of Adjuvant Bisphosphonates and Other Bone-Modifying Agents in Breast Cancer: ASCO-OH (CCO) Guideline Update.

Purpose: To update recommendations of the American Society of Clinical Oncology (ASCO)-Ontario Health (Cancer Care Ontario [CCO]) adjuvant bone-modifying agents in breast cancer guideline.

Methods: An Expert Panel conducted a systematic review to identify new, potentially practice-changing data.

Results: Four articles met eligibility criteria and form the evidentiary basis for revision of the previous recommendations.

Genome-Wide DNA Methylation Signatures Predict the Early Asymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer.

Chemotherapy with doxorubicin (DOX) may cause unpredictable cardiotoxicity. This study aimed to determine whether the methylation signature of peripheral blood mononuclear cells (PBMCs) prior to and after the first cycle of DOX-based chemotherapy could predict the risk of cardiotoxicity in breast cancer patients. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) by >10%.

Alpelisib-Induced Diabetic Ketoacidosis in a Non-diabetic Patient.

Alpelisib is a phosphoinositol-3-kinase alpha catalytic subunit (PIK3CA) inhibitor used in patients with PIK3CA mutated breast cancer. The phosphatidylinositol 3-kinase (PI3K) pathway is responsible for activating protein kinase-B (AKT), and activated AKT promotes translation of glucose transporter 4 and glycogen synthesis in insulin-responsive tissues. Therefore, it is perhaps not surprising that hyperglycemia is the most common side effect of alpelisib, though diabetic ketoacidosis (DKA) appears to be a rare complication.

Genomic and Transcriptomic Profiling of Brain Metastases.

Brain metastases (BM) are the most common brain tumors in adults occurring in up to 40% of all cancer patients. Multi-omics approaches allow for understanding molecular mechanisms and identification of markers with prognostic significance. In this study, we profile 130 BM using genomics and transcriptomics and correlate molecular characteristics to clinical parameters.

P10s-PADRE vaccine combined with neoadjuvant chemotherapy in ER-positive breast cancer patients induces humoral and cellular immune responses.

Breast cancer patients diagnosed with HR+/HER2- tumors face a persistent risk of distant recurrence long after completion of their treatment. Strategies to induce anti-tumor immune responses could complement standard-of-care therapies for these patients. The current study was performed to examine the feasibility, safety and immunogenicity of adding P10s-PADRE to standard-of-care chemotherapy in HR+/HER2- early-stage breast cancer patients.

Serial single-cell genomics reveals convergent subclonal evolution of resistance as early-stage breast cancer patients progress on endocrine plus CDK4/6 therapy.

Combining cyclin-dependent kinase (CDK) inhibitors with endocrine therapy improves outcomes for metastatic estrogen receptor positive (ER+) breast cancer patients but its value in earlier stage patients is unclear. We examined evolutionary trajectories of early-stage breast cancer tumors, using single cell RNA sequencing (scRNAseq) of serial biopsies from the FELINE clinical trial (#NCT02712723) of endocrine therapy (letrozole) alone or combined with the CDK inhibitor ribociclib. Despite differences in subclonal diversity evolution across patients and treatments, common resistance phenotypes emerged.

Subclinical doxorubicin-induced cardiotoxicity update: role of neutrophils and endothelium.

Doxorubicin (DOX) is a highly effective chemotherapy agent that often causes cardiotoxicity. Despite a number of extensive studies, the risk for DOX cardiotoxicity remains unpredictable. The majority of the studies on DOX-induced cardiotoxicity have been focused on the effects on cardiomyocytes that lead to contractile dysfunction.

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries.

Evidence for Early Stage Anti-Tumor Immunity Elicited by Spatially Fractionated Radiotherapy-Immunotherapy Combinations.

The combination of radiotherapy and immunotherapy may generate synergistic anti-tumor host immune responses and promote abscopal effects. Spatial fractionation of a radiation dose has been found to promote unique physiological responses of tumors, which might promote synergy with immunotherapy. To determine whether spatial fractionation may augment immune activity, whole-tumor or spatial fractionation grid radiation treatment (GRID) alone or in combination with antibodies against immune checkpoints PD1 and CTLA-4 were tested in an immunocompetent mouse model using a triple negative breast tumor (4T1).

Biomarkers of inflammation, hypercoagulability and endothelial injury predict early asymptomatic doxorubicin-induced cardiotoxicity in breast cancer patients.

Doxorubicin (DOX)-induced cardiotoxicity is a major limitation to its clinical application. Cardiotoxicity of DOX is dose-dependent that begins with the first dose. Oxidative stress and inflammation are involved in DOX-related cardiotoxicity.

Proteogenomic analysis of melanoma brain metastases from distinct anatomical sites identifies pathways of metastatic progression.

Melanoma brain metastases (MBM) portend a grim prognosis and can occur in up to 40% of melanoma patients. Genomic characterization of brain metastases has been previously carried out to identify potential mutational drivers. However, to date a comprehensive multi-omics approach has yet to be used to analyze brain metastases.

Association of DNA-Methylation Profiles With Immune Responses Elicited in Breast Cancer Patients Immunized With a Carbohydrate-Mimicking Peptide: A Pilot Study.

Immune response to a given antigen, particularly in cancer patients, is complex and is controlled by various genetic and environmental factors. Identifying biomarkers that can predict robust response to immunization is an urgent need in clinical cancer vaccine development. Given the involvement of DNA methylation in the development of lymphocytes, tumorigenicity and tumor progression, we aimed to analyze pre-vaccination DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) from breast cancer subjects vaccinated with a novel peptide-based vaccine referred to as P10s-PADRE.

Practical Vitamin D Supplementation Using Machine Learning.

Background: Patients with breast cancer are at increased risk of developing osteoporosis. Maintaining normal levels of vitamin D may decrease the risk of osteoporosis, and vitamin D levels must be corrected in patients who develop osteoporosis before beginning bone modifying agents. Therefore, it is important to correct insufficient vitamin D levels in a timely manner.

Genome-wide DNA methylation signatures to predict pathologic complete response from combined neoadjuvant chemotherapy with bevacizumab in breast cancer.

ClinicalTrials.gov Identifier: NCT00203502.

Immunotherapy Outcomes in Advanced Melanoma in Relation to Age.

Introduction: Older age is a melanoma risk factor. Elderly individuals are likelier to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, it is believed that elderly people cannot mount a potent immune response to checkpoint inhibitors to eliminate melanoma.

Primary Breast Carcinoma of the Vulva Metastatic to Lymph Nodes and Bones: A Case Report and Literature Review.

Introduction: Primary breast carcinoma can occur at ectopic sites. The axilla is the most common site of ectopic primary breast cancer, but presentation in the vulva is rare. We discuss a rare presentation of primary breast carcinoma of the vulva with distant lymph node and bone metastases in a premenopausal woman.