Precision therapeutics and emerging strategies for HR-positive metastatic breast cancer.

Anti-oestrogen-based therapies, often combined with a CDK4/6 inhibitor, are the current standard-of-care first-line therapy for patients with advanced-stage hormone receptor-positive (HR) breast cancer. Resistance to anti-oestrogen agents inevitably occurs, mediated by oestrogen receptor (ER)-dependent or ER-independent mechanisms that drive tumour progression. Emerging endocrine therapies include, but are not limited to, next-generation oral ER degraders and proteolysis targeting chimeras, which might be particularly effective in patients with ESR1-mutant breast cancer.

CDK4/6 Inhibitor Efficacy in -Mutant Metastatic Breast Cancer.

Background: In estrogen receptor-positive metastatic breast cancer, mutations (ESR1) are a common mechanism of acquired resistance to aromatase inhibitors (ArIh). However, the impact alterations have on CDK4/6 inhibitor (CDK4/6i) sensitivity has not been established. Analyses of CDK4/6i trials suggest that the endocrine therapy partner and specific allele may affect susceptibility.

Artificial intelligence for triaging of breast cancer screening mammograms and workload reduction: A meta-analysis of a deep learning software.

Objective: Deep learning (DL) has shown promising results for improving mammographic breast cancer diagnosis. However, the impact of artificial intelligence (AI) on the breast cancer screening process has not yet been fully elucidated in terms of potential workload reduction. We aim to assess if AI-based triaging of breast cancer screening mammograms could reduce the radiologist's workload with non-inferior sensitivity.

A Gene Panel Associated With Abemaciclib Utility in -Mutated Breast Cancer After Prior Cyclin-Dependent Kinase 4/6-Inhibitor Progression.

Purpose: For patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC), first-line treatment is endocrine therapy (ET) plus cyclin-dependent kinase 4/6 inhibition (CDK4/6i). After disease progression, which often comes with resistance mutations (ESR1-MUT), which therapies to use next and for which patients are open questions. An active area of exploration is treatment with further CDK4/6i, particularly abemaciclib, which has distinct pharmacokinetic and pharmacodynamic properties compared with the other approved CDK4/6 inhibitors, palbociclib and ribociclib.

Artificial intelligence for prediction of treatment outcomes in breast cancer: Systematic review of design, reporting standards, and bias.

Background: Artificial intelligence (AI) has the potential to personalize treatment strategies for patients with cancer. However, current methodological weaknesses could limit clinical impact. We identified common limitations and suggested potential solutions to facilitate translation of AI to breast cancer management.

Mechanisms of Resistance to CDK4/6 Blockade in Advanced Hormone Receptor-positive, HER2-negative Breast Cancer and Emerging Therapeutic Opportunities.

The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have become the standard of care, in combination with antiestrogen therapy, for patients with hormone receptor-positive (HR+)/HER2- advanced breast cancer. Various preclinical and translational research efforts have begun to shed light on the genomic and molecular landscape of resistance to these agents. Drivers of resistance to CDK4/6i therapy can be broadly subdivided into alterations impacting cell-cycle mediators and activation of oncogenic signal transduction pathways.

Clinico-genomic profiling and clonal dynamic modeling of -aberrant myelodysplastic syndrome and acute myeloid leukemia.

-aberrant myelodysplastic syndrome and acute myeloid leukemia have dismal outcomes. Here, we define the clinico-genomic landscape of disruptions in 40 patients and employ clonal dynamic modeling to map the mutational hierarchy against clinical outcomes. Most mutations (45.

Niche-directed therapy in acute myeloid leukemia: optimization of stem cell competition for niche occupancy.

Acute myeloid leukemia (AML) is an aggressive malignancy of stem cell origin that contributes to significant morbidity and mortality. The long-term prognosis remains dismal given the high likelihood for primary refractory or relapsed disease. An essential component of relapse is resurgence from the bone marrow.

pulmonary abscess and pleural space infection in an immunocompetent patient.

A 34-year-old woman is admitted to the hospital with dyspnoea, dry cough and left-sided flank pain. Her urinary test was positive and CT imaging demonstrated multifocal pneumonia with pulmonary abscesses. Although she had initial clinical improvement on appropriate antibiotic therapy, her hospital course was complicated by worsening flank pain, hypoxemia and leucocytosis, prompting clinical re-evaluation and assessment for development of complications involving the pleural space.

Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience.

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor-positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i.

Patients And Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers.

Genomic Characterization of Metastatic Breast Cancer.

Purpose: In contrast to recurrence after initial diagnosis of stage I-III breast cancer [recurrent metastatic breast cancer (rMBC)], metastatic breast cancer (dnMBC) represents a unique setting to elucidate metastatic drivers in the absence of treatment selection. We present the genomic landscape of dnMBC and association with overall survival (OS).

Experimental Design: Targeted DNA sequencing (OncoPanel) was prospectively performed on either primary or metastatic tumors from 926 patients (212 dnMBC and 714 rMBC).

The Genomic Landscape of Intrinsic and Acquired Resistance to Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with Hormone Receptor-Positive Metastatic Breast Cancer.

Mechanisms driving resistance to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in hormone receptor-positive (HR) breast cancer have not been clearly defined. Whole-exome sequencing of 59 tumors with CDK4/6i exposure revealed multiple candidate resistance mechanisms including loss, activating alterations in , and , and loss of estrogen receptor expression. experiments confirmed that these alterations conferred CDK4/6i resistance.

Phase II study of ruxolitinib, a selective JAK1/2 inhibitor, in patients with metastatic triple-negative breast cancer.

Preclinical data support a role for the IL-6/JAK2/STAT3 signaling pathway in breast cancer. Ruxolitinib is an orally bioavailable receptor tyrosine inhibitor targeting JAK1 and JAK2. We evaluated the safety and efficacy of ruxolitinib in patients with metastatic breast cancer.