Accurate Screening for Early-Stage Breast Cancer by Detection and Profiling of Circulating Tumor Cells

SIMPLE SUMMARY: Detection of breast cancer in the early stages is associated with higher cure rates and better survival, and also requires fewer intensive treatments. Current breast cancer screening via mammography is unsuitable for use among (younger) women with more dense breasts, and also has limitations in its ability to detect aggressive breast cancers. In this research article, we describe a breast cancer detection test that is based on the detection of ‘circulating tumor cells’ in blood samples. This test can detect breast cancer CTCs with high accuracy across all age groups, hormone receptor subtypes, histological subtypes, and disease grade. In our study, this test detected breast cancer cases and differentiated them from healthy (cancer-free) females as well as those with non-cancerous conditions with high accuracy. This test has negligible risk of false positive findings, as well as high detection rate for early-stage (localized) breast cancer. Clinical adoption of this test can be beneficial in cancer screening as well as in detection of breast cancers in suspected cases. ABSTRACT: Background: The early detection of breast cancer (BrC) is associated with improved survival. We describe a blood-based breast cancer detection test based on functional enrichment of breast-adenocarcinoma-associated circulating tumor cells (BrAD-CTCs) and their identification via multiplexed fluorescence immunocytochemistry (ICC) profiling for GCDFP15, GATA3, EpCAM, PanCK, and CD45 status. Methods: The ability of the test to differentiate BrC cases (N = 548) from healthy women (N = 9632) was evaluated in a case–control clinical study. The ability of the test to differentiate BrC cases from those with benign breast conditions was evaluated in a prospective clinical study of women (N = 141) suspected of BrC. Results: The test accurately detects BrAD-CTCs in breast cancers, irrespective of age, ethnicity, disease stage, grade, or hormone receptor status. Analytical validation established the high accuracy and reliability of the test under intended use conditions. The test detects and differentiates BrC cases from healthy women with 100% specificity and 92.07% overall sensitivity in a case–control study. In a prospective clinical study, the test shows 93.1% specificity and 94.64% overall sensitivity in differentiating breast cancer cases (N = 112) from benign breast conditions (N = 29). Conclusion: The findings reported in this manuscript support the clinical potential of this test for blood-based BrC detection.