Abstract
Simple SummaryCirculating tumor DNA is DNA released by the tumor into the bloodstream. In breast cancer, it is used mainly in research or in clinical trials, but it will likely be used in routine clinical practice once certain issues have been worked out and methods of analysis have been improved and standardized. Breast cancer classification and treatment selection are now based on analysis of the tumor but circulating tumor DNA carries many features of the original tumor and can be analyzed from a simple, non-invasive blood extraction. Here, we review its potential role in early breast cancer (for screening, diagnosis, detection of minimal residual disease after surgery, follow up, and treatment) and in metastatic breast cancer (for the detection of mutations, prognosis and treatment). Breast cancer is currently classified by immunohistochemistry. However, technological advances in the detection of circulating tumor DNA (ctDNA) have made new options available for diagnosis, classification, biological knowledge, and treatment selection. Breast cancer is a heterogeneous disease and ctDNA can accurately reflect this heterogeneity, allowing us to detect, monitor, and understand the evolution of the disease. Breast cancer patients have higher levels of circulating DNA than healthy subjects, and ctDNA can be used for different objectives at different timepoints of the disease, ranging from screening and early detection to monitoring for resistance mutations in advanced disease. In early breast cancer, ctDNA clearance has been associated with higher rates of complete pathological response after neoadjuvant treatment and with fewer recurrences after radical treatments. In metastatic disease, ctDNA can help select the optimal sequencing of treatments. In the future, thanks to new bioinformatics tools, the use of ctDNA in breast cancer will become more frequent, enhancing our knowledge of the biology of tumors. Moreover, deep learning algorithms may also be able to predict breast cancer evolution or treatment sensitivity. In the coming years, continued research and the improvement of liquid biopsy techniques will be key to the implementation of ctDNA analysis in routine clinical practice.
Highlights
Customized panel detected 75% at baseline; Slow decrease in Circulating Tumor DNA (ctDNA) during neoadjuvant chemotherapy was associated with shorter survival ctDNA detection during follow up was associated with a high rate of relapse ctDNA detection before neoadjuvant anti-human epidermal growth factor 2 (HER2) therapy was associated with low pathological complete response (pCR) rates targeted digital sequencing (TARDIS) results were informative in
Measurement of ctDNA methylation has been proposed as a method to predict resistance to adjuvant tamoxifen treatment [60], and serum DNA methylation has been proposed as a surrogate marker of tumor DNA methylation for diagnosis and prognosis [61]
The application of liquid biopsy and ctDNA analysis in breast cancer opens a window of opportunity that encompasses all possible disease situations: from early diagnosis, through the detection of minimal residual disease (MRD), the early detection of relapse, and the monitoring and treatment planning for advanced disease
Summary
The Role of Circulating Tumor DNA (ctDNA) in Breast Cancer. The selection of breast cancer treatment is based on the analysis of tumor biopsy. The information obtained from the tumor biopsy is not permanent, and changes and acquired resistance that can occur during cancer treatment cannot be evaluated or analyzed in the original tumor specimen. Tumor biopsy is still the gold standard for diagnosis, classification, and treatment decisions, there is a growing interest in improving precision medicine by characterizing and monitoring the tumor genome in blood samples [10], known as liquid biopsy. A liquid biopsy can contain circulating tumor cells (CTCs), ctDNA, and exosomes that can help to understand tumor evolution, resistance, and heterogeneity during treatment [11]. In some cases, a tumor biopsy may not be feasible, and a liquid biopsy would be the only method to obtain a diagnosis or knowledge of the tumor biology
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