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Heterogeneity and tumor evolution reflected in liquid biopsy in metastatic breast cancer patients: a review

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Abstract

Breast cancer is a spatially and temporally dynamic disease in which differently evolving genetic clones are responsible for progression and clinical outcome. We review tumor heterogeneity and clonal evolution from studies comparing primary tumors and metastasis and discuss plasma circulating tumor DNA as a powerful real-time approach for monitoring the clonal landscape of breast cancer during treatment and recurrence. We found only a few early studies exploring clonal evolution and heterogeneity through analysis of multiregional tissue biopsies of different progression steps in comparison with circulating tumor DNA (ctDNA) from blood plasma. The model of linear progression seemed to be more often reported than the model of parallel progression. The results show complex routes to metastasis, however, and plasma most often reflected metastasis more than primary tumor. The described patterns of evolution and the polyclonal nature of breast cancer have clinical consequences and should be considered during patient diagnosis and treatment selection. Current studies focusing on the relevance of clonal evolution in the clinical setting illustrate the role of liquid biopsy as a noninvasive biomarker for monitoring clonal progression and response to treatment. In the clinical setting, circulating tumor DNA may be an ideal support for tumor biopsies to characterize the genetic landscape of the metastatic disease and to improve longitudinal monitoring of disease dynamics and treatment effectiveness through detection of residual tumor after resection, relapse, or metastasis within a particular patient.

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Acknowledgements

The authors thank medical writer Claire Gudex for her contribution to editing this review.

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Authors and Affiliations

  1. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark

    Stephanie Kavan, Torben A. Kruse & Mads Thomassen

  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Stephanie Kavan, Torben A. Kruse, Marianne Vogsen, Malene G. Hildebrandt & Mads Thomassen

  3. Department of Oncology, Odense University Hospital, Odense, Denmark

    Marianne Vogsen

  4. Department of Nuclear Medicine, Odense University Hospital, Odense, Denmark

    Malene G. Hildebrandt

  5. Centre for Personalized Response Monitoring in Oncology (PREMIO), Odense University Hospital, Odense, Denmark

    Malene G. Hildebrandt & Mads Thomassen

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Kavan, S., Kruse, T.A., Vogsen, M. et al. Heterogeneity and tumor evolution reflected in liquid biopsy in metastatic breast cancer patients: a review. Cancer Metastasis Rev 41, 433–446 (2022). https://doi.org/10.1007/s10555-022-10023-9

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