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Author Notes:

Timothy Crook, tr.crook@gmail.com; Tel.: +44-775-3442-921

Conceptualization, T.C., R.L., K.M., A.T., M.M., R.P., A.V., R.M., A.R., S.L., D.P., D.A., V.D., P.F., S.S., A.S. and R.D.; data curation, S.A. and A.S.; formal analysis, D.P., D.A., P.F., S.A. and A.S.; funding acquisition, R.D.; investigation, T.C., D.P., D.A., V.D. and R.D.; methodology, T.C., R.L., K.M., A.T., M.M., R.P., A.V., R.M., A.R., S.L., D.P., D.A., V.D., P.F., S.A., S.S., A.S. and R.D.; project administration, D.P., D.A., V.D. and P.F.; resources, T.C., D.P., D.A., V.D., P.F., S.A. and R.D.; software, D.P., D.A., S.A., A.S. and R.D.; supervision, T.C., D.P., D.A., V.D., P.F., A.S. and R.D.; validation, D.P., D.A., P.F., S.A., A.S. and R.D.; visualization, D.P., D.A., P.F., S.A., A.S. and R.D.; writing—original draft, A.S. and R.D.; writing—review and editing, T.C., R.L., K.M., A.T., M.M., R.P., A.V., R.M., A.R., S.L., D.P., D.A., V.D., P.F., S.A., S.S., A.S. and R.D. All authors have read and agreed to the published version of the manuscript.

The authors are grateful to the staff of the study sponsor (DCG) for their contributions in managing various clinical, operational, and laboratory aspects of the study.

Timothy Crook, Robert Leonard, Alastair Thompson, Michael Michell, Ashok Vaid, Ravi Mehrotra, Anantbhushan Ranade, and Sewanti Limaye have no competing interests. Kefah Mokbel and Raymond Page are fractional stock holders of the Study Sponsor. Darshana Patil, Dadasaheb Akolkar, Vineet Datta, Pradip Fulmali, Sachin Apurwa, Stefan Schuster, and Ajay Srinivasan are employees of the Study Sponsor. Rajan Datar is the founder of the Study Sponsor.

Subjects:

Research Funding:

No external funding was obtained for this study. The entire study was funded by the study sponsor (DCG).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • breast cancer
  • screening
  • circulating tumor cells
  • immunocytochemistry
  • CARCINOMA IN-SITU
  • ADHESION MOLECULE
  • EPCAM EXPRESSION
  • MAMMOGRAPHY
  • US
  • RECOMMENDATION
  • DISSEMINATION
  • DENSITY
  • BLOOD

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

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Journal Title:

CANCERS

Volume:

Volume 14, Number 14

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Type of Work:

Article | Final Publisher PDF

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.

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© 2022 by the authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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