Molecular Characterization, Via Next-Generation Sequencing, of Refractory or Resistant Invasive Breast Carcinoma

Abstract

The most frequently diagnosed neoplasia in the world in 2020 was breast cancer (BC). On top of its high incidence, unexpected behavior as recurrence in patients, in spite of appropriate therapies, reaches 20%-30%. We believe that some molecular characteristics of tumors may lead to this bad behavior, and we can identify them with next-generation sequencing (NGS). We made a retrospective multicentric study, conducted to molecularly characterize, by means of a custom NGS panel, cases diagnosed with treatment-refractory or treatment-resistant invasive breast carcinoma, studied in formalin-fixed paraffin-embedded (FFPE) samples. The panel included 50 genes related to tumorigenesis, cancer evolution and targeted therapies. Twelve cases were included from three centers. Alterations of driver genes were found in all of the cases, and 75% harbored mutations in TP53. Furthermore, we found alterations that could be therapeutic targets in half of the patients, such as mutations in PIK3CA (33% cases), mTOR (8.3%) or BRCA1 (8.3%). Other significant molecular alterations were: the loss of SWI-SNF complex´s components, modified genes of the MAP kinase pathway and alterations in epidermal growth factor receptor (EGFR). Not all of them are known targets but prognostic significance was found. We conclude that NGS characterization of breast cancer in FFPE samples is a reproducible technique that can provide prognostic and predictive information about our patients and therefore, constitutes, in the near future, a valuable clinical tool in the context of precision medicine.