Abstract 5932: Novel screening technology for early detection of breast cancer using liquid biopsy

Abstract

Abstract Breast cancer screening is the first line-of-defense in detecting this disease early, and consequently changing its outcomes, dramatically. We introduce Crystalogram as a novel, radiation-free, blood-based, breast cancer screening tool, for asymptomatic adult women of all ages, regardless of their risk level. While Crystalogram could be used in tandem with Mammogram, it has unique characteristics that could make it effective as an independent tool, particularly for those who currently have no standard-of-care recommendation for breast screening, i.e., asymptomatic, average risk women younger than 40 or 45 in the U.S. or Europe, respectively. In the realm of cancer screening, positive predictive value (PPV) plays a crucial role. A low or moderate PPV (as in Mammogram) could result in a large number of false positive patients, who would subsequently have to undergo unnecessary tests, some of which are invasive, such as tissue biopsy. By targeting a remarkably high PPV, Crystalogram is aimed to (while offering an attractive sensitivity) reduce the number of false positive patients, and hence offer a true screening platform. Most methods for cancer screening are based on either imaging or (if molecular) cell-free tumor DNA (ctDNA). Crystalogram uses circulating tumor cells (CTCs) in conjunction with whole genome sequencing (WGS). Molecular analyses using CTCs pose many technical challenges; however (unlike ctDNA) they provide a complete view of a cell, and hence the related cellular perturbations that are indicative of breast cancer. In ctDNA-based cancer screening methods, the source of nucleic acid for each sequenced fragment is lost. In a CTC-based system, however, the source of all sequenced fragments (i.e., cells they originate from) is known. Additionally, since the nucleic acid for each cell is independently amplified, the number of available fragments per cell is significantly higher as compared to ctDNA originating from comparable cells. Through a CTC-based and molecular technology, Crystalogram can deliver a superior PPV for breast cancer screening, and at a reasonable sensitivity. This is particularly true for breast cancer subtypes that have more dire outcomes and yet evade current screening modalities (e.g., triple negative breast cancer). The crux of Crystalogram’s high specificity is its two-tiered architecture, where a sample may be called negative at either of the two subsystems (in series), each of which is highly specific: 1) Sample Qualification System (SQS), which operates on a relationship built on the proprietary antibody staining features of the cells along with their physical properties; 2) Whole Genome Sequencing (WGS), where the sample can be marked as negative if it does not show the expected proprietary signatures for breast cancer. Since SQS and WGS systems are in series, a modest specificity of 99% for each subsystem would result in a specificity of 99.99% for the complete Crystalogram system. Citation Format: Bahram G. Kermani. Novel screening technology for early detection of breast cancer using liquid biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5932.