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Circulating tumour cells and cell-free DNA as tools for managing breast cancer

Abstract

Circulating blood biomarkers promise to become non-invasive real-time surrogates for tumour tissue-based biomarkers. Circulating biomarkers have been investigated as tools for breast cancer diagnosis, the dissection of breast cancer biology and its genetic and clinical heterogeneity, prognostication, prediction and monitoring of therapeutic response and resistance. Circulating tumour cells and cell-free plasma DNA have been analysed in retrospective studies, and the assessment of these biomarkers is being incorporated into clinical trials. As the scope of breast cancer intratumour genetic heterogeneity unravels, the development of robust and standardized methods for the assessment of circulating biomarkers will be essential for the realization of the potentials of personalized medicine. In this Review, we discuss the current status of blood-born biomarkers as surrogates for tissue-based biomarkers, and their burgeoning impact on the management of patients with breast cancer.

Key Points

  • Circulating blood biomarkers represent promising non-invasive real-time surrogates for tumour tissue-based biomarkers

  • In breast cancer, circulating biomarkers have been investigated as tools for diagnosis, prognostication, prediction, monitoring of therapeutic response, and resistance

  • Circulating tumour cells and cell-free plasma DNA have been analysed in retrospective studies, and the assessment of these biomarkers is being incorporated into clinical trials

  • Longitudinal analyses of circulating biomarkers are likely to constitute useful tools to address intratumour genetic heterogeneity and therapeutic resistance in both the adjuvant and metastatic breast cancer settings

  • The current challenges include the need for standardization methods for the assessment and interpretation of circulating biomarkers, and the determination of their clinical utility for patients with breast cancer

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Figure 1: HER2-positive breast cancer with heterogeneous HER2 overexpression and gene amplification.
Figure 2: Hypothesis for intratumour heterogeneity, therapeutic resistance and the potential role of blood-born circulating biomarkers.

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Acknowledgements

The authors acknowledge Fundación Rafael del Pino for research support.

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L. De Mattos-Arruda, L. Santarpia, J. S. Reis-Filho and J. Seoane researched data for the article. L. De Mattos-Arruda, J. Cortes, L. Santarpia, J. Tabernero, J. S. Reis-Filho and J. Seoane made a substantial contribution to discussion of content and wrote the manuscript. All authors reviewed and edited the article before submission.

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Correspondence to Leticia De Mattos-Arruda.

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De Mattos-Arruda, L., Cortes, J., Santarpia, L. et al. Circulating tumour cells and cell-free DNA as tools for managing breast cancer. Nat Rev Clin Oncol 10, 377–389 (2013). https://doi.org/10.1038/nrclinonc.2013.80

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