Circulating Tumor DNA and Biomarker Analyses From the LOTUS Randomized Trial of First-Line Ipatasertib and Paclitaxel for Metastatic Triple-Negative Breast Cancer.

Purpose: Combining the oral AKT inhibitor ipatasertib with paclitaxel as first-line therapy for metastatic triple-negative breast cancer significantly improved progression-free survival (PFS) in the placebo-controlled, randomized, phase II LOTUS trial, with a more pronounced effect in patients with -altered tumors. We report findings from the extensive translational research program.

Patients And Methods: Pretreatment plasma and tumor samples were evaluated for genetic alterations using FoundationACT and FoundationOne (Foundation Medicine, Cambridge, MA) hybrid capture next-generation sequencing assays, respectively.

Analytical Validation of a Hybrid Capture-Based Next-Generation Sequencing Clinical Assay for Genomic Profiling of Cell-Free Circulating Tumor DNA.

Genomic profiling of circulating tumor DNA derived from cell-free DNA (cfDNA) in blood can provide a noninvasive method for detecting genomic biomarkers to guide clinical decision making for cancer patients. We developed a hybrid capture-based next-generation sequencing assay for genomic profiling of circulating tumor DNA from blood (FoundationACT). High-sequencing coverage and molecular barcode-based error detection enabled accurate detection of genomic alterations, including short variants (base substitutions, short insertions/deletions) and genomic re-arrangements at low allele frequencies (AFs), and copy number amplifications.

The clinical significance of K-ras mutation in endometrial "surface epithelial changes" and their associated endometrial adenocarcinoma.

Objectives: The entity of 'surface epithelial changes' (SECs) was first described in 1995 [1]. Morphologically, SECs usually arise from malignant glands at the superficial aspect of well differentiated (WD) endometrioid carcinomas (ECs) and impart the appearance of a 'maturational' phenomenon at the surface of the cancer. Exhibiting a paradoxically bland histologic appearance, SECs typically show morphologic features that mimic benign entities, particularly endocervical microglandular hyperplasia (MGH).

KRAS Mutations in Mucinous Lesions of the Uterus.

Objectives: The current study examined the KRAS mutation status in a spectrum of mucinous lesions of the uterus, including mucinous metaplasia (MM), atypical mucinous proliferation (AMP), endocervical mucosa, and microglandular hyperplasia (MGH).

Methods: Thirty-nine cases, including 15 AMPs, nine MMs, nine MGHs, and six normal endocervical mucosas, were selected from the departmental archive. All AMP cases with follow-up biopsies or hysterectomies were reviewed.