RESUMEN
In 1940, it was demonstrated that free DNA could be identified in the bloodstream. It was later shown that circulating nucleic acids (CNA), both DNA and RNA, are present in several neoplastic and non-neoplastic diseases, and that in cancer they originate mostly from the tumor. In this review, we discuss the potential application of CNA as a breast cancer biomarker for early diagnosis and patient evaluation. Most of the initial studies on CNA compared the levels of CNA in cancer patients and healthy individuals. To increase sensitivity and specificity, cancer-specific molecular alterations were then utilized. In this respect, epigenetic alterations and microRNA offer considerable advantages over mutations because of their easiness of detection. Epigenetic signatures, being early events of carcinogenesis, may also be valuable markers for screening purposes. Monitoring the follow-up of the patients is one of the most interesting applications of CNA-based assays, and it is reasonable to hypothesize that CNA may become a surrogate marker for circulating cancer cells in the prediction of patient outcome. Transferring these findings to the clinical practice is the next effort, and this will be possible when a 'common language' is defined to allow proper validation of these new markers.