Multi-platform biomarkers of response to an immune checkpoint inhibitor in the neoadjuvant I-SPY 2 trial for early-stage breast cancer.

Only a subset of patients with breast cancer responds to immune checkpoint blockade (ICB). To better understand the underlying mechanisms, we analyze pretreatment biopsies from patients in the I-SPY 2 trial who receive neoadjuvant ICB using multiple platforms to profile the tumor microenvironment. A variety of immune cell populations and markers of immune/cytokine signaling associate with pathologic complete response (pCR).

Early Ascertainment of Breast Cancer Diagnoses Comparing Self-Reported Questionnaires and Electronic Health Record Data Warehouse: The WISDOM Study.

Purpose: The goal of this study was to use real-world data sources that may be faster and more complete than self-reported data alone, and timelier than cancer registries, to ascertain breast cancer cases in the ongoing screening trial, the WISDOM Study.

Methods: We developed a data warehouse procedural process (DWPP) to identify breast cancer cases from a subgroup of WISDOM participants (n = 11,314) who received breast-related care from a University of California Health Center in the period 2012-2021 by searching electronic health records (EHRs) in the University of California Data Warehouse (UCDW). Incident breast cancer diagnoses identified by the DWPP were compared with those identified by self-report via annual follow-up online questionnaires.

Development and testing of a polygenic risk score for breast cancer aggressiveness.

Aggressive breast cancers portend a poor prognosis, but current polygenic risk scores (PRSs) for breast cancer do not reliably predict aggressive cancers. Aggressiveness can be effectively recapitulated using tumor gene expression profiling. Thus, we sought to develop a PRS for the risk of recurrence score weighted on proliferation (ROR-P), an established prognostic signature.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

Background: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments.

Patients And Methods: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms.

Treacherous Elasticity, Callous Boundaries: Aspiring Volunteer Initiatives in the Field of Refugee Support in Rotterdam.

This contribution focuses on volunteer initiatives that seek to assist refugee status holders in Rotterdam. It studies initiatives that are still in the process of fine-tuning their focus, grappling for funds, searching for volunteers, and seeking collaborations. The article lays bare the inequalities that such aspiring initiatives can be premised on and produce.

A case-case analysis of women with breast cancer: predictors of interval vs screen-detected cancer.

Purpose: The Breast Cancer Surveillance Consortium (BCSC) model is a widely used risk model that predicts 5- and 10-year risk of developing invasive breast cancer for healthy women aged 35-74 years. Women with high BCSC risk may also be at elevated risk to develop interval cancers, which present symptomatically in the year following a normal screening mammogram. We examined the association between high BCSC risk (defined as the top 2.

RAB5A expression is a predictive biomarker for trastuzumab emtansine in breast cancer.

HER2 is a predictive biomarker for HER2-targeted therapeutics. For antibody-drug conjugates (ADCs; e.g.

Toward developing a metastatic breast cancer treatment strategy that incorporates history of response to previous treatments.

Background: Information regarding response to past treatments may provide clues concerning the classes of drugs most or least likely to work for a particular metastatic or neoadjuvant early stage breast cancer patient. However, currently there is no systematized knowledge base that would support clinical treatment decision-making that takes response history into account.

Methods: To model history-dependent response data we leveraged a published in vitro breast cancer viability dataset (84 cell lines, 90 therapeutic compounds) to calculate the odds ratios (log (OR)) of responding to each drug given knowledge of (intrinsic/prior) response to all other agents.

Contralateral prophylactic mastectomy: A narrative review of the evidence and acceptability.

The uptake of contralateral prophylactic mastectomy (CPM) has increased steadily over the last twenty years in women of all age groups and breast cancer stages. Since contralateral breast cancer is relatively rare and the breast cancer guidelines only recommend CPM in a small subset of patients with breast cancer, the drivers of this trend are unknown. This review aims to evaluate the evidence for and acceptability of CPM, data on patient rationales for choosing CPM, and some of the factors that might impact patient preferences.

Noncirrhotic Extrahepatic Portosystemic Shunt Causing Adult-Onset Encephalopathy Treated with Endovascular Closure.

A 54-year-old woman presented with a six-month history of episodic confusion and progressive ataxia. A comprehensive metabolic panel was notable for elevated values of alkaline phosphatase (161 U/L), total bilirubin (1.5 mg/dL), and serum ammonia of 300 umol/L (normal range 9-47).

Mobile DNA in cancer. Extensive transduction of nonrepetitive DNA mediated by L1 retrotransposition in cancer genomes.

Long interspersed nuclear element-1 (L1) retrotransposons are mobile repetitive elements that are abundant in the human genome. L1 elements propagate through RNA intermediates. In the germ line, neighboring, nonrepetitive sequences are occasionally mobilized by the L1 machinery, a process called 3' transduction.

Honeybees prefer warmer nectar and less viscous nectar, regardless of sugar concentration.

The internal temperature of flowers may be higher than air temperature, and warmer nectar could offer energetic advantages for honeybee thermoregulation, as well as being easier to drink owing to its lower viscosity. We investigated the responses of Apis mellifera scutellata (10 colonies) to warmed 10% w/w sucrose solutions, maintained at 20-35°C, independent of low air temperatures, and to 20% w/w sucrose solutions with the viscosity increased by the addition of the inert polysaccharide Tylose (up to the equivalent of 34.5% sucrose).

Genome-wide association studies identify four ER negative-specific breast cancer risk loci.

Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS).

Large-scale genotyping identifies 41 new loci associated with breast cancer risk.

Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping.

The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase.

Background: The MINDACT (Microarray In Node-negative and 1-3 node positive Disease may Avoid ChemoTherapy) trial investigates the clinical utility of the 70-gene profile (MammaPrint) for the selection of breast cancer patients for adjuvant chemotherapy (CT) together with standard clinicopathological criteria. We present the results of the pilot phase consisting of first 800 patients included.

Methods: MINDACT has enrolled 6600 patients, classified into high or low risk by MammaPrint and clinicopathological risk through Adjuvant! Online.

Retinoic acid resistance of the variant embryonal carcinoma cell line RAC65 is caused by expression of a truncated RAR alpha.

P19 embryonal carcinoma (EC) cells differentiate when treated with retinoic acid (RA). The P19 EC-derived mutant cell line RAC65 is resistant to the differentiation-inducing activity of RA. We show that these cells express a truncated retinoic acid receptor alpha(mRAR alpha-RAC65), probably due to the integration of a transposon-like element in the RAR alpha gene.

Cytotoxicity of methotrexate and trimetrexate and its reversal by folinic acid in human leukemic CCRF-CEM cells with carrier-mediated and receptor-mediated folate uptake.

The cytotoxic effects of the antifolates methotrexate (MTX) and trimetrexate (TMQ) were investigated for two human leukemic CCRF-CEM cell lines, one expressing the "classical" reduced folate/MTX carrier (CEM-RF), another lacking this carrier but expressing a membrane associated folate binding protein (CEM-FBP). CEM-FBP cells were found to be highly resistant to MTX compared to CEM-RF cells, especially in short exposures. For example, after 4 h incubation, IC50 values for MTX were 251 microM and 0.

The esophagogastric polyp-fold complex.

A polyp-fold complex at the gastroesophageal junction is a rare finding. We made this diagnosis in a 51-year-old man who presented with abdominal discomfort after an episode of protracted vomiting. The esophagogastric polyp-fold complex is not always associated with reflux esophagitis, as was originally proposed.

Chemotherapy for gastrointestinal malignancy.

Cancers of gastrointestinal tract are frequently unresectable at the time of diagnosis and the prognosis for these patients is discouraging. Chemotheapy is often administered in an attempt to prolong life or at least alleviate symptoms. Esophageal squamous cell carcinoma is notoriously refractory to chemotherapy.