A headlight on liquid biopsies: a challenging tool for breast cancer management

Abstract

Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g., PI3K/Akt/mTOR, PTEN, TP53). To date, diagnosis and metastasis monitoring is mainly carried out through tissue biopsy and/or re-biopsy, a very invasive procedure limited only to certain locations and not always feasible in clinical practice. In order to improve disease monitoring over time and to avoid painful procedure such as tissue biopsy, liquid biopsy may represent a new precious tool. Indeed, it represents a basin of “new generation” biomarkers that are spread into the bloodstream from both primary and metastatic sites. Moreover, elevated concentrations of circulating tumor DNA (ctDNA) as well as circulating tumor cells (CTCs) have been found in blood plasma of patients with various tumor types. Nowadays, several new approaches have been introduced for the detection and characterization of CTCs and ctDNA, allowing a real-time monitoring of tumor evolution. This review is focused on the clinical relevance of liquid biopsy in breast cancer and will provide an update concerning CTCs and ctDNA utility as a tool for breast cancer patient monitoring during the course of disease

Cell-Free DNA and Circulating Tumor Cells: Comprehensive Liquid Biopsy Analysis in Advanced Breast Cancer

“…PIK3CA mutations are very frequent (20%-40%) genetic alterations in MBC, particularly in node-negative, ER þ and HER2 À breast cancer, and are generally related to a good clinical outcome with a lower recurrence and mortality rate (35). Nevertheless, tissue-based NGS had already demonstrated that at least 33% of TN breast cancer have deregulated PI3K/AKT pathways, making these pathways an attractive target for pharmacologic treatment (e.g., everolimus) and highlighting the importance of mutation profiling for individualized therapies (36).…”

“…In our population, maybe because enriched in IBC (64% of the patients), with a rate of 40% in the entire population and of 31% in the TN subgroup, PIK3CA/mTOR pathway (altered in 22 patients, including 12 patients with IBC) appears the second most altered pathway, immediately after TP53 (52% and 61%, in the entire population and TN subgroup respectively). Indeed, the mutations in the TP53 gene are relevant in breast carcinogenesis, with a frequency up to 83% in basal-like tumors (35). Among the patients with HER2 þ disease, HER2 alteration is the second most frequent.…”

Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

“…PI3K/AKT/mTOR (PAM) represents the main signaling pathway responsible for cell proliferation, survival, metabolism and motility regulation and is often activated in BC [ 51 - 54 ] (Figure 1 ). A heterodimeric molecule belonging to the lipid kinases, phosphoinositide 3-kinase (PI3K), is the major component of this pathway.…”

Liquid Biopsy in Non-Small Cell Lung Cancer (NSCLC)

“…Therefore, the molecular analysis of the tumor and/or of the metastatic lesions is becoming more and more requested at the time of PD. Unfortunately, tissue biopsy is a procedure often limited by several features, including its invasiveness, the not easy access to different tumor sites, the high intra-tumor heterogeneity, and not ultimately the low patients' compliance [20]. Thus, in the last decade, many new noninvasive approaches have been studied to overcome the aforementioned issues.…”