Outpatient parenteral antimicrobial therapy (OPAT) for the management of periprosthetic joint infections in the Republic of Ireland (ROI) from 2013 to 2021.

Objectives: Periprosthetic joint infection (PJI) is a complication of joint arthroplasty and is seen in 1-2% of cases. Since its initiation in 2013, the national outpatient parenteral antimicrobial therapy (OPAT) program has facilitated the outpatient management of intravenous antimicrobials for PJI. This study aims to describe the clinical epidemiology of patients on OPAT with PJI between 2013 and 2021.

A phenocopy signature of TP53 loss predicts response to chemotherapy.

In preclinical studies, p53 loss of function impacts chemotherapy response, but this has not been consistently validated clinically. We trained a TP53-loss phenocopy gene expression signature from pan-cancer clinical samples in the TCGA. In vitro, the TP53-loss phenocopy signature predicted chemotherapy response across cancer types.

Breast Cancer Index in Premenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer.

Importance: Adjuvant ovarian function suppression (OFS) with oral endocrine therapy improves outcomes for premenopausal patients with hormone receptor-positive (HR+) breast cancer but adds adverse effects. A genomic biomarker for selecting patients most likely to benefit from OFS-based treatment is lacking.

Objective: To assess the predictive and prognostic performance of the Breast Cancer Index (BCI) for OFS benefit in premenopausal women with HR+ breast cancer.

Impact of systemic disease on CNS disease control after stereotactic radiosurgery to breast cancer brain metastases (The SYBRA Study).

The objective of the study is to assess impact of systemic disease (SD) status on overall survival and brain metastasis (BM) control, adopting a novel landmark approach to categorize SD among breast cancer (BC) patients. This single institution retrospective study included BCBM patients who have received stereotactic radiosurgery (SRS) to brain. Separate endpoints [CNS failure-free survival (cFFS), overall survival (OS)] were analyzed from each Landmark (LM): LM1 (3-months), LM2 (6-months).

Oral SERD, a Novel Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer.

Breast cancer is the most common cancer among women worldwide, and estrogen receptor-positive (ER+) breast cancer accounts for a significant proportion of cases. While various treatments are available, endocrine therapies are often the first-line treatment for this type of breast cancer. However, the development of drug resistance poses a significant challenge in managing this disease.

Ethnic disparities and COVID-19 pneumonia in Ireland: a single-centre descriptive study of hospitalised patients in a tertiary university teaching hospital.

In this study, we aim to describe the demographic, clinical and imaging characteristics, treatment course and subsequent outcomes of the first 116 cases presenting to a tertiary Dublin hospital with COVID-19 infection and to compare whether ethnic minority background was a risk factor for poorer disease outcomes in this cohort. Of 116 cases analysed, 100 (86%) patients presented from the community, 6 (5%) from care homes and 10 (9%) were existing inpatients. Fifty-four (46%) patients identified as being from an ethnic minority group.

SARS-CoV-2 transmission risk for common group activities and settings: a living scoping review.

Background: While the modes of transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are well studied, the risk of transmission in various group settings or activities is less clear. This living scoping review aims to summarize the risk factors of coronavirus disease 2019 (COVID-19) spread in common group activities (e.g.

The Efficacy of CB-103, a First-in-Class Transcriptional Notch Inhibitor, in Preclinical Models of Breast Cancer.

Background: The efficacy of CB-103 was evaluated in preclinical models of both ER+ and TNBC. Furthermore, the therapeutic efficacy of combining CB-103 with fulvestrant in ER+ BC and paclitaxel in TNBC was determined.

Methods: CB-103 was screened in combination with a panel of anti-neoplastic drugs.

Is the Androgen Receptor a Viable Target in Triple Negative Breast Cancer in 5 Years?

Triple negative breast cancer (TNBC) is characterized by high rates of disease recurrence after definitive therapy, and median survival of less than 18 months in the metastatic setting. Systemic therapy options for TNBC consist primarily of cytotoxic chemotherapy-containing regimens, and while recently FDA-approved chemo-immunotherapy combinations and antibody-drug conjugates such as Sacituzumab govitecan have improved clinical outcomes, there remains an unmet need for more effective and less toxic therapies. A subset of TNBC expresses the androgen receptor (AR), a nuclear hormone steroid receptor that activates an androgen-responsive transcriptional program, and gene expression profiling has revealed a TNBC molecular subtype with AR expression and luminal and androgen responsive features.

A review of treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm.

The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)-status to HER2-low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2-low expression has emerged as a targetable biomarker, and anti-HER2 antibody-drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2-low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor-positive and triple-negative BC needs to be reconsidered, as approximately half of these BCs are HER2-low.

Fragmentomic analysis of circulating tumor DNA-targeted cancer panels.

Background: The isolation of cell-free DNA (cfDNA) from the bloodstream can be used to detect and analyze somatic alterations in circulating tumor DNA (ctDNA), and multiple cfDNA-targeted sequencing panels are now commercially available for Food and Drug Administration (FDA)-approved biomarker indications to guide treatment. More recently, cfDNA fragmentation patterns have emerged as a tool to infer epigenomic and transcriptomic information. However, most of these analyses used whole-genome sequencing, which is insufficient to identify FDA-approved biomarker indications in a cost-effective manner.

Margetuximab in HER2-positive metastatic breast cancer.

Several anti-HER2 agents are approved for third-line treatment and beyond (after first-line and second-line); however, no specific treatment strategy is recommended for third-line and beyond. Although these agents improve disease outcomes, HER2-positive metastatic breast cancer remains incurable and there is an unmet need for effective therapies in the later line setting. This review focuses on the development of margetuximab-cmkb, a novel, Fc-engineered, anti-HER2 monoclonal antibody, and its role in the systemic treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease.

Risk of Recurrence in Patients With HER2+ Early-Stage Breast Cancer: Literature Analysis of Patient and Disease Characteristics.

Human epidermal growth factor receptor 2 (HER2) overexpression occurs in 15% to 20% of patients with early-stage breast cancers (EBCs). Without HER2-targeted therapy, 30% to 50% of patients relapse within 10 years, many developing incurable metastatic disease. This literature review was designed to identify and validate patient- and disease-related factors associated with recurrence in patients with HER2+ EBC.

Using Oncotype DX breast recurrence score® assay to define the role of neoadjuvant endocrine therapy in early-stage hormone receptor-positive breast cancer.

Purpose: The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need.

Methods: We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay.

Systemic Therapy Approaches for Breast Cancer Brain and Leptomeningeal Metastases.

Brain metastasis arising from breast cancer is associated with a poor prognosis. Various systemic chemotherapy and targeted therapies which are effective against breast cancer often fail to provide benefits against brain metastasis. This is mainly due to limited penetration of the therapies across the blood-brain barrier, and divergent evolution of brain metastasis compared to the primary tumor.

Inflammatory breast cancer with excellent response to pembrolizumab-chemotherapy combination: A case report.

Inflammatory breast cancer (IBC) is a rare variety of breast cancer accounting for two percent of breast cancer diagnoses in the United States. It is characterized by peau d'orange, breast edema and erythema on physical examination and dermal lymphatic invasion by tumor emboli on histological examination. Micrometastases to lymphatics and bone marrow at the time of diagnosis and angiogenic properties of IBC explain the high propensity of this cancer to relapse and metastasize, its aggressiveness and poor prognosis.