Clinical monitoring of minimal residual disease and treatment response is routinely performed in several hematological malignancies with known pathognomonic chromosomal rearrangements (e.g. BCR-ABL) or mutations (NPM1) (Dolken, Adv Cancer Res 2001). We now know in all cancer types studied, cancer-derived DNA (termed cell-free circulating tumor DNA; ctDNA) can be found in the blood circulation and usually comprises a small fraction of the total circulating DNA (Jung et al., Clin Chim Acta 2010). Circulating DNA is rapidly degraded into short fragments, and the quantity of ctDNA appears to be related to tumor progression (Diehl et al., Nat Med 2008; Jung et al., Clin Chim Acta 2010; Bettegowda et al., Sci Transl Med 2014). Therefore, ctDNA is an attractive biomarker for non-invasive monitoring of tumor dynamics. Indeed, serial measurement of ctDNA including my group’s work has shown encouraging results for several solid cancer types (Diehl et al., Nat Med 2008; Leary et al., Sci Transl Med 2010; McBride et al., Genes Chromosomes Cancer 2010; Olsson et al., EMBO Mol Med 2015), and in the metastatic breast cancer setting, measurement of ctDNA dynamics appears to be superior to the biomarkers CA 15-3 and circulating tumor cells (Dawson et al., N Engl J Med 2013). Across most studies, ctDNA levels appear to yield strong prognostic value. Moreover, liquid biopsy ctDNA tests can be used to identify targetable and actionable mutations in a minimally-invasive way, which can potentially reduce the number of invasive tissue biopsies and thereby lower healthcare costs and medical complications. In this project we continue our work on ultrasensitive monitoring of cancer patients using ctDNA liquid biopsy analyses, and focus on a number of malignancies, in particular breast cancer.