Abstract
Circulating tumor DNA (ctDNA) has emerged as a non-invasive “liquid biopsy” for early breast cancer diagnosis. We evaluated the suitability of ctDNA analysis in the diagnosis of early breast cancer after mammography findings, comparing PIK3CA and TP53 mutations between tumor biopsies and pre-biopsy circulating DNA. Matched plasma and frozen fresh tissue biopsies from patients with Breast Imaging-Reporting and Data System (BIRADS) 4c/5 mammography findings and subsequent diagnosis of primary breast cancer were analyzed using NGS TruSeq Custom Amplicon Low Input Panel (Illumina) and plasma SafeSEQ (Sysmex Inostics). The same plasma and tumor mutations were observed in eight of 29 patients (27.6%) with four in TP53 and five in PIK3CA mutations. Sequencing analysis also revealed four additional ctDNA mutations (three in TP53 and one in PIK3CA) previously not identified in three patients tissue biopsy. One of these patients had mutations in both genes. Age, tumor grade and size, immunohistochemical (IHC) subtype, BIRADS category, and lymph node positivity were significantly associated with the detectability of these blood tumor-derived mutations. In conclusion, ctDNA analysis could be used in early breast cancer diagnosis, providing critical clinical information to improve patient diagnosis.
Highlights
Breast cancer (BC) is the most common cancer in females worldwide, the second most common cause of death from cancer among males and females, and a leading cause of premature mortality from cancer as measured by average and total years of life lost [1].GLOBOCAN estimated that there would be about 2.1 million newly diagnosed cases of female breast cancer in 2018, accounting for almost one in four cancer cases among women worldwide [2]
The aim of the present study was to investigate whether Circulating tumor DNA (ctDNA) analysis can be used in early breast cancer diagnosis, by sequencing plasma DNA taken before tumor biopsy in patients with mammographic findings
We found a trend for a higher plasma ctDNA mutation burden in patients with clinical characteristics associated with more aggressive disease factors such as higher tumor grade, and tumor size, Breast Imaging-Reporting and Data System (BIRADS) category 5, the presence of positive lymph nodes and the IHC subtype present, being more frequently mutated in luminal A tumors followed by luminal B tumors
Summary
Breast cancer (BC) is the most common cancer in females worldwide, the second most common cause of death from cancer among males and females (only preceded by lung cancer), and a leading cause of premature mortality from cancer as measured by average and total years of life lost [1]. GLOBOCAN estimated that there would be about 2.1 million newly diagnosed cases of female breast cancer in 2018, accounting for almost one in four cancer cases among women worldwide [2]. The current standard of care for BC screening is mammography [4]. Radiologists use the BIRADS (Breast Imaging-Reporting and Data System) criteria to describe the probability of a mammographic finding to be a malignant tumor [5], currently, it is still necessary to perform a biopsy of the lesion to confirm the diagnosis. Time-consuming, and in some cases not amenable for repetition. In many cases, these biopsies do not reflect the intratumor heterogeneity, which may have important consequences for personalized-medicine approaches that commonly rely on single tumor-biopsy samples to portray tumor mutational landscapes [6]
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