ctDNA Use as a Prognostic Marker in Breast Cancer Patients

Breast cancer remains the most frequently diagnosed malignancy among women, accounting for nearly 30% of all new cancer diagnoses in women in the USA. Due to early detection and improvements in treatment, breast cancer mortality has decreased steadily over the past two decades. However, gaining further understanding of breast cancer metastasis is necessary, as 25% of non-metastatic breast cancer patients will develop distant metastases after initially successful treatment.Furthermore, 10–50% of patients with negative axillary lymph nodes at the time of curative surgery later develop distant metastasis. Together, these data suggest that bloodstream tumor cell dissemination (circulating tumor cells, CTCs) and distant micrometastases that are undetectable by currently available diagnostic tools can develop during the early stages of breast cancer progression. CTCs have been identified as the potential source of micrometastases responsible for treatment failures and have become an active area of translational cancer research. As cells undergo apoptosis, necrosis, and macrophage phagocytosis, they release nucleic acid fragments called cfDNA into the bloodstream. A subset of cfDNA, called circulating tumor DNA (ctDNA). ctDNA levels have been shown to correlate well with changes in tumor burden and appear promisingly as a potential tool for monitoring the progression of breast cancer. Performing serial analysis of ctDNA in plasma samples over time has allowed the tracking of genomic evolution in response to therapy. At this time, ctDNA has not yet been validated as a marker for routine, direct use at the treatment level; however, there are many potential applications, including residual disease detection following treatment, noninvasive tumor genotyping, and early detection of relapse