Although liquid biopsy remains challenging due to the importance of pre-analytics, the small amounts of ctDNA and the requirement of sensitive detection techniques we were able to identify SPAG6, PER1 and NKX2-6 as potential blood-borne biomarkers for early breast cancer detection, which showed in combination with ITIH5 a sensitivity of 64% for breast cancer detection. Here, NKX2-6 is linked to breast cancer.