Blood-based tests for multicancer early detection (PATHFINDER): a prospective cohort study.

Background: Multicancer early detection (MCED) blood tests can detect a cancer signal from circulating cell-free DNA (cfDNA). PATHFINDER was a prospective cohort study investigating the feasibility of MCED testing for cancer screening.

Methods: In this prospective cohort study done in oncology and primary care outpatient clinics at seven US health networks, a convenience sample of adults aged 50 years or older without signs or symptoms of cancer consented to MCED testing.

The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice.

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e.

Perturbed myoepithelial cell differentiation in BRCA mutation carriers and in ductal carcinoma in situ.

Myoepithelial cells play key roles in normal mammary gland development and in limiting pre-invasive to invasive breast tumor progression, yet their differentiation and perturbation in ductal carcinoma in situ (DCIS) are poorly understood. Here, we investigated myoepithelial cells in normal breast tissues of BRCA1 and BRCA2 germline mutation carriers and in non-carrier controls, and in sporadic DCIS. We found that in the normal breast of non-carriers, myoepithelial cells frequently co-express the p63 and TCF7 transcription factors and that p63 and TCF7 show overlapping chromatin peaks associated with differentiated myoepithelium-specific genes.

Immune Escape in Breast Cancer During to Invasive Carcinoma Transition.

To investigate immune escape during breast tumor progression, we analyzed the composition of leukocytes in normal breast tissues, ductal carcinoma (DCIS), and invasive ductal carcinomas (IDC). We found significant tissue and tumor subtype-specific differences in multiple cell types including T cells and neutrophils. Gene expression profiling of CD45CD3 T cells demonstrated a decrease in CD8 signatures in IDCs.

Self administered screening for hereditary cancers in conjunction with mammography and ultrasound.

We evaluated the feasibility of an automated tablet computer application providing a family and personal history based cancer risk assessment for hereditary breast, ovarian, endometrial and colorectal cancers. 1,002 women presenting for screening mammography and 1,000 presenting for ultrasound were offered screening. The application calculated the risk of BRCA mutations using BRCAPRO, Myriad and Tyrer-Cuzick risk assessment models.