Analytical Validation of the ForeCYTE Breast Health Test

Abstract

Introduction: The ForeCYTE Breast Health Test provides a 10-year and lifetime breast cancer risk stratification using family history of breast and ovarian cancer, personal reproductive history, and cytological evaluation of exfoliated cells present in nipple aspirate fluid (NAF) in the risk stratification algorithm developed by TyrerCuzick. Materials and Methods: Specimens of NAF are collected on membrane filters with one of two FDA-cleared biopsy instruments, the Halo or the Mammary Aspiration Specimen Cytology Test (MASCT) System devices, are fixed upon collection by spraying the membrane filters with a 0.1 mL mist of Saccomanno's fixative. The specimen filters are processed in situ for NAF protein using a colloidal gold assay with a limit of detection of 0.1 ng of protein (corresponding to 1 pL of NAF) and a linear range to 1,000 ng. The filters are then stained with a modified Papanicolaou stain and morphological criteria applied to establish a diagnosis. Results: Spiked MCF-7 breast cancer cells demonstrate quantitative recovery (94.7%) in the range of 1-10 cancer cells/membrane filter with a sensitivity for identifying a cellular specimen of 100% at 4-100 cells/membrane and 75% at 2 cells/membrane and 50% at 1 cell /membrane. If hyperplasia is noted and morphology is inadequate