Real-World comprehensive genomic profiling data for diagnostic clarity in pulmonary Large-Cell neuroendocrine carcinoma.

Background: Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is an uncommon subtype of lung cancer believed to represent a spectrum of tumors sharing characteristics of both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Other groups have proposed genomic LCNEC subtypes, including small cell-like, non-small cell-like, and carcinoid-like subtypes. The primary goal of this study was to better define the NSCLC-like subtype with comprehensive genomic profiling (CGP).

The Molecular, Immunologic, and Clinicodemographic Landscape of MYC-Amplified Advanced Prostate Cancer.

Background: MYC is a commonly amplified, potentially targetable gene in prostate cancer (PCa). We sought to define the molecular, immunologic, and clinicodemographic landscape of MYC amplification (MYC) in advanced PCa to establish a rationale for personalized treatment combinations.

Methods: Hybrid capture-based comprehensive genomic profiling (CGP) was performed on PCa tumor samples.

Quantifying the Value of Multigene Testing in Resected Early Stage Lung Adenocarcinoma.

Introduction: Tyrosine kinase inhibitors and immune checkpoint inhibitors (ICIs), each requiring testing for precision biomarkers, have recently been approved in the adjuvant setting. We assessed the potential value of multigene testing in early lung adenocarcinoma (LUAD).

Methods: Using a real-world clinicogenomic database linking deidentified electronic health record-derived clinical data to genomic data, we selected patients with LUAD who underwent tissue comprehensive genomic profiling (CGP).

Biology and Targetability of the Extended Spectrum of PIK3CA Mutations Detected in Breast Carcinoma.

Purpose: Alpelisib is a PI3K alpha (PI3Kα)-selective inhibitor approved for the treatment of hormone receptor-positive/HER2-negative (HR+/HER2-) PIK3CA-mutated advanced breast cancer (ABC) based on the SOLAR-1 trial, which defined 11 substitutions in exons 7, 9, and 20 in PIK3CA (SOLAR1m). We report alpelisib effectiveness for ABC harboring SOLAR1m, as well as other pathogenic PIK3CA mutations (OTHERm) using comprehensive genomic profiling (CGP).

Experimental Design: A total of 33,977 tissue and 1,587 liquid biopsies were analyzed using hybrid capture-based CGP covering the entire coding sequence of PIK3CA.

APOBEC Mutational Signatures in Hormone Receptor-Positive Human Epidermal Growth Factor Receptor 2-Negative Breast Cancers Are Associated With Poor Outcomes on CDK4/6 Inhibitors and Endocrine Therapy.

Purpose: APOBEC mutagenesis underlies somatic evolution and accounts for tumor heterogeneity in several cancers, including breast cancer (BC). In this study, we evaluated the characteristics of a real-world cohort for time-to-treatment discontinuation (TTD) and overall survival on CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) and immune checkpoint inhibitors.

Methods: Comprehensive genomic profiling results from 29,833 BC samples were analyzed for tumor mutational burden and APOBEC signatures.

Genomic Biomarkers and Genome-Wide Loss-of-Heterozygosity Scores in Metastatic Prostate Cancer Following Progression on Androgen-Targeting Therapies.

Purpose: To study the impact of standard-of-care hormonal therapies on metastatic prostate cancer (mPC) clinical genomic profiles in real-world practice, with a focus on homologous recombination-repair (HRR) genes.

Patients And Methods: Targeted next-generation sequencing of 1,302 patients with mPC was pursued using the FoundationOne or FoundationOne CDx assays. Longitudinal clinical data for correlative analysis were curated via technology-enabled abstraction of electronic health records.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy by Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer.

Importance: The most useful biomarkers for clinical decision-making identify patients likely to have improved outcomes with one treatment vs another.

Objective: To evaluate treatment class-specific outcomes of patients receiving immune checkpoint inhibitor (ICI) vs taxane chemotherapy by tumor mutational burden (TMB).

Design, Setting, And Participants: This comparative effectiveness analysis of clinical variables and outcomes used prospectively defined biomarker-stratified genomic data from a deidentified clinicogenomic database.

Predictive Genomic Biomarkers of Hormonal Therapy Versus Chemotherapy Benefit in Metastatic Castration-resistant Prostate Cancer.

Background: Biomarkers predicting second-generation novel hormonal therapy (NHT) benefit relative to taxanes are critical for optimized treatment decisions for metastatic castration-resistant prostate cancer (mCRPC) patients. These associations have not been reported simultaneously for common mCRPC genomic biomarkers.

Objective: To evaluate predictive associations of common genomic aberrations in mCRPC using an established comprehensive genomic profiling (CGP) system.

Patient with Lobular Carcinoma of the Breast and Activating AKT1 E17K Variant.

Objective: To present the characteristics of the AKT1E117K gene variant and a description of the clinical application in a patient with metastatic breast cancer.

Results: 63 y/o woman with Stage IV Invasive lobular carcinoma at diagnosis was treated with Palbociclib and aromatase inhibitors (AI). At progression, tissue was sent for comprehensive genomic profiling to Foundation Medicine (FM) which revealed AKT1E17K mutation.