Figure 1.

Schematic of metastatic progression of breast cancer and potential for liquid biopsy. (A) The primary tumor cancer cells harbor high levels of genome instability that under pressure from chemotherapy (CT^X) respond with both enhanced DNA damage repair (DDR) and mutation rates. Altered cells acquire oncogenic phenotypes including EMT allowing single cell dissemination from the primary tumor. (B) Entering the bloodstream clustered circulating tumor cells bind platelets to evade immune response and gain survival signaling. (C) Circulating tumor cells extravasate to the secondary site supported by ECM. (D) Cells that die in response to CTx are the source of circulating DNA. (E) Cell free DNA is usually 80–200 bp, however when associated within a vesicle can be up to 10 kb. (F) Liquid biopsy of ~7 ml is taken from a patient to sample CTC numbers and cfDNA for sequencing.