ESR1 Y537S and D538G mutations drive resistance to CDK4/6 inhibitors in estrogen receptor-positive breast cancer.

Purpose: Breast cancers with ESR1 mutations are resistant to antiestrogen therapy. In this study, we aimed to investigate the association of ESR1 mutations with resistance to CDK4/6 inhibitors (CDK4/6i) using real-world data analysis and experimental validation.

Patients And Methods: A total of 3,958 patients with estrogen receptor-positive (ER+) metastatic breast cancer with DNA sequencing data were analyzed.

Neratinib Efficacy in Patients With EGFR Exon 18-Mutant Non-Small-Cell Lung Cancer: Findings From the SUMMIT Basket Trial.

Background: Activating mutations in the epidermal growth factor receptor (EGFR) gene occur in 7% to 23% of patients with non-small-cell lung cancer (NSCLC). A small proportion of these (3-5%) are exon 18 mutations. Neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), had activity in the phase II SUMMIT basket study.

Mapping cellular interactions from spatially resolved transcriptomics data.

Cell-cell communication (CCC) is essential to how life forms and functions. However, accurate, high-throughput mapping of how expression of all genes in one cell affects expression of all genes in another cell is made possible only recently through the introduction of spatially resolved transcriptomics (SRT) technologies, especially those that achieve single-cell resolution. Nevertheless, substantial challenges remain to analyze such highly complex data properly.

TICT, and Deep-Blue Electroluminescence from Acceptor-Donor-Acceptor Molecules.

Donor-acceptor (D-A) materials based on butterfly-shaped molecules could inhibit exciton-migration-induced quenching due to molecular twist. To explore this attribute towards beneficial photophysical properties, three novel bipolar acceptor-donor-acceptor (A-D-A) molecules with triphenyl triazine end capping along with substitution ortho to the Tröger's base (TB) scaffold varying from H, Me, and F were explored. The installation of H/Me/F imparted an electron push-pull effect with concomitant maneuvering of photophysical properties.

A Tale of Two Hospitals: Effect of Access to Care Through a Safety Net Hospital on Adjuvant Therapy, Imaging Compliance and 5-Year Survival Rates Compared to the University Hospital Served by the Same Breast Cancer Clinical Teams.

Rationale And Objectives: To compare rates of guideline-concordant care, imaging surveillance, recurrence and survival outcomes between a safety-net (SNH) and tertiary-care University Hospital (UH) served by the same breast cancer clinical teams.

Materials And Methods: 647 women with newly diagnosed breast cancer treated in affiliated SNH and UH between 11.1.

Robotic Kidney Transplant Beyond the Learning Curve: 8-Year Single-center Experience and Matched Comparison With Open Kidney Transplant.

Objective: To investigate the medium to long-term outcomes of robotic-assisted kidney transplantation (RAKT) and propensity-matched comparison with open kidney transplant (OKT).

Materials And Methods: We retrospectively reviewed 342 patients from database, who underwent RAKT and OKT from January 2015 to May 2022, at our center. Various demographic, intraoperative, and postoperative parameters were evaluated.

Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.

Background: HER2 mutations are targetable alterations in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC). In the SUMMIT basket study, patients with HER2-mutant MBC received neratinib monotherapy, neratinib + fulvestrant, or neratinib + fulvestrant + trastuzumab (N + F + T). We report results from 71 patients with HR+, HER2-mutant MBC, including 21 (seven in each arm) from a randomized substudy of fulvestrant versus fulvestrant + trastuzumab (F + T) versus N + F + T.

Aspirin use is associated with improvement in distant metastases outcome in patients with residual disease after neoadjuvant chemotherapy.

Purpose: Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients.

The Utility of Breast Cancer Index (BCI) Over Clinical Prognostic Tools for Predicting the Need for Extended Endocrine Therapy: A Safety Net Hospital Experience.

Introduction: Extended endocrine therapy (EET) benefits select patients with early-stage hormone-receptor positive (HR+) breast cancer (BC) but also incurs side effects and cost. The Clinical Treatment Score at Five Years (CTS5) is a free tool that estimates risks of late relapse in estrogen-receptor positive (ER+) BC using clinicopathologic factors. The Breast Cancer Index (BCI) incorporates 2 genomic assays to estimate late relapse risk and likelihood of benefit from EET.

Spontaneous Cerebrospinal Fluid Rhinorrhea in End Stage Renal Disease.

We report a case of spontaneous cerebrospinal fluid (CSF) rhinorrhea in a patient on maintenance hemodialysis. There was no previous history of trauma or surgery. Secondary hyperparathyroidism due to progression of chronic kidney disease (CKD) and a rise in intracranial pressure resulted in spontaneous cerebrospinal fluid rhinorrhea.

A Phase I/Ib Trial of PD 0332991 (Palbociclib) and T-DM1 in HER2-Positive Advanced Breast Cancer After Trastuzumab and Taxane Therapy.

Background: Preclinical breast cancer models with acquired HER2 resistance exhibit decreased proliferation with CDK4/6 inhibition in tumors with intact Rb and low p16 levels. Adding cytotoxic agents like T-DM1 enhances the inhibitory CDK4/6 cytostatic effect.

Patients And Methods: A phase I/Ib 3+3 dose escalation/expansion trial of palbociclib and T-DM1 identified 150 mg on days 5 to 18 as the palbociclib maximal tolerated dose combined with day 1 intravenous T-DM1 in 21-day treatment cycles.

Clinicopathological Features and Outcomes in Individuals with Breast Cancer and ATM, CHEK2, or PALB2 Mutations.

Introduction: The moderate-penetrance germline mutations ATM, CHEK2, and PALB2 are implicated in an increased risk of the development of breast cancer. Whether these mutations provide clinical utility to guide treatment strategies and prognosis remains unknown.

Methods: A retrospective case-control study from a tertiary institution compared patients with stage 0-III breast cancer, and positive for ATM, CHEK2, or PALB2 mutations, with a matched cohort selected by randomization and negative for mutations.

The Changing Paradigm for the Treatment of HER2-Positive Breast Cancer.

For decades, HER2-positive breast cancer was associated with poor outcomes and higher mortality rates than other breast cancer subtypes. However, the advent of Trastuzumab (Herceptin) has significantly changed the treatment paradigm of patients afflicted with HER2-positive breast cancer. The discovery of newer HER2-targeted therapies, such as Pertuzumab (Perjeta), has further added to the armamentarium of treating HER2-positive breast cancers.

Patient familiarity with, understanding of, and preferences for clinical trial endpoints and terminology.

Background: Although there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding, and perceptions of this content.

Methods: Maximum difference scaling (MaxDiff) methodology was used to develop a survey for assessing patients' understanding of 19 clinical terms and perceived importance of 9 endpoint surrogate phrases used in clinical trials and consent forms. The survey was administered electronically to individuals with metastatic breast cancer affiliated with the Metastatic Breast Cancer Alliance.

An evaluation of fulvestrant for the treatment of metastatic breast cancer.

: Fulvestrant is currently the only selective estrogen receptor degrader (SERD) that is approved for clinical use in estrogen receptor (ER) positive advanced breast cancer (ABC). The drug is approved as single-agent therapy in the first and second-line setting of metastatic ER-positive breast cancer. : In this review, the authors review the preclinical studies that were pivotal in the development of fulvestrant, the pharmacologic properties of the drug, and the key clinical trials that resulted in its approval for clinical use.

Neurological Monitoring in Acute Liver Failure.

Cerebral oedema and Intracranial Hypertension (ICH) are serious complications of acute liver failure affecting approximately 30% of patients, resulting in neurological injury or death. Multiple pathogenetic mechanisms contribute to the pathogenesis of HE including circulating neurotoxins such as ammonia, systemic and neuro-inflammation, infection and cerebral hyperaemia due to loss of cerebral vascular autoregulation. Early recognition and diagnosis is often difficult as clinical signs of elevated Intracranial Pressure (ICP) are not uniformly present and maybe masked by other organ support.

LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells.

Neratinib: Inching Up on the Cure Rate of HER2 Breast Cancer?

Neratinib was recently approved by the FDA for extended adjuvant treatment of HER2 breast cancer. The ExteNET trial showed improvement in invasive disease-free survival (iDFS) in the neratinib arm compared with placebo. The benefit was more pronounced in patients with estrogen receptor-positive (ER)/HER2 tumors, suggesting bidirectional cross-talk between the ER and HER pathways.