With 2.1 million new diagnoses worldwide in 2018, breast cancer is the most prevalent neoplasm in the female population globally, but also the one that can be cured best, often definitively and with nondemolishing methods, especially if it is diagnosed early, when it is still very small and not very aggressive. For this reason, regular breast self-examination and, starting at age 45-50, mammography every two years are recommended for all women to detect any minute masses that are not perceptible by touch but are already potentially risky, to be biopsied and then subjected to histological and molecular analysis to characterize them precisely and identify optimal treatment. In the near future, this already highly efficient approach may be enriched with new noninvasive diagnostic system based on the analysis of circulating tumor DNA (ctDNA), i.e., DNA fragments released into the bloodstream from aged and destroyed breast cancer cells. The ctDNA can be obtained by a simple blood draw and analyzed by an extremely precise and rapid sequencing technique called NGS (Next Generation Sequencing), aimed at detecting certain genetic mutations that are distinctively present in the DNA of breast cancer cells. The first data supporting the clinical utility of this method, termed “liquid biopsy,” come from a pilot study, coordinated by researchers at the University of Málaga (Spain), which compared the diagnostic sensitivity of the new ctDNA test before classical tissue biopsy with that of molecular analysis after classical tissue biopsy, using mutations in the PIK3CA and TP53 genes as markers. The evaluation resulted in identifying identical mutations in 8 of the 29 patients considered (27.6%): four in TP53 and five in PIK3CA. In addition, analysis with NGS on ctDNA revealed four additional genetic mutations (three in TP53 and one in PIK3CA), which had not been reported by molecular analysis of breast tissue taken by classical biopsy: which underscores the high sensitivity of “liquid biopsy” at an early stage. One of these patients had mutations in both genes under consideration. The likelihood of testing positive for markers on ctDNA examined with NGS was higher in women who were younger, had larger tumor masserella and higher imaging scores on mammography (indicative of a higher probability of actually having cancer). At the moment, the new test is still being evaluated and not available in clinical practice, but if upcoming studies confirm the performance and diagnostic sensitivity highlighted the “liquid biopsy” may soon join the classical one in the early detection of breast cancer and, perhaps, one day supplant it. In this way, women with positive mammograms, but not necessarily breast cancer, could be prevented from having their suspected breast tissue harvested for diagnostic purposes.
Source: Rodriguez BJ et al. Detection of TP53 and PIK3CA Mutations in Circulating Tumor DNA Using Next-Generation Sequencing in the Screening Process for Early Breast Cancer Diagnosis. J Clin Med 2019;8:1183-1207; doi:10.3390/jcm8081183
