Unveiling the Potential of Liquid Biopsy in HER2-Positive Breast Cancer Management

Abstract

Invasive breast cancer (BC) is the most common cancer in women with a slightly increasing yearly incidence. BC immunohistochemical characterisation is a crucial tool to define the intrinsic nature of each tumour and personalise BC patients’ clinical management. In this regard, the characterisation of human epidermal growth factor receptor 2 (HER2) status guides physicians to treat with therapies tailored to this membrane receptor. Standardly, a tumour solid biopsy is therefore required, which is an invasive procedure and has difficulties to provide the complete molecular picture of the tumour. To complement these standard-of-care approaches, liquid biopsy is a validated methodology to obtain circulating tumour components such as circulating tumour DNA (ctDNA) and circulating tumour cells (CTCs) from body fluids in an easy-to-perform minimal-invasive manner. However, its clinical validity in cancer is still to be demonstrated. This review focusses on the utilisation of both ctDNA and CTCs in early and metastatic HER2-positive BC tumours. We discuss recently published studies deciphering the capacity of liquid biopsy to determine the response to neoadjuvant and adjuvant therapies as well as to predict patients’ outcomes.

Phase II study to investigate the efficacy of trastuzumab biosimilar (Herzuma®) plus treatment of physician's choice (TPC) in patients with heavily pretreated HER-2+ metastatic breast cancer (KCSG BR 18–14/KM10B)

“…However, in a recent study evaluating ERBB2 mutations using ctDNA in patients with advanced breast cancer, the frequency of ERBB2 mutations was 8.9% and this was higher in HER2-positive tumors than in HER2-negative tumors [ 26 ]. It has been suggested that ERBB2 mutations are acquired as a consequence of anti-HER2 therapy, which can easily be detected by ctDNA analysis [ 26 , 27 ]. In addition, ERBB2 mutations were associated with shorter PFS in HER2-positive patients who received trastuzumab plus chemotherapy in a metastatic setting.…”

Potential utility of miRNAs for liquid biopsy in breast cancer

“…For BC diagnosis, a solid biopsy is a well-established technique in clinics that provides information about tumor histology and subtype. Nonetheless, mishaps in the detection of alternative biomarkers, insufficient tissue obtention, or incompatibility with long-term monitoring, among other limitations still exist ( 5 ). Compared with solid biopsy, LB is a more comprehensive diagnostic test that uses blood, urine ( 67 ), saliva, and other biological fluids ( 68 , 69 ).…”

“…Additionally, in LB, invasiveness and residual disease are minimized that also enables and simplifies the longitudinal monitoring of BC patients. LB potentiates obtaining the complete molecular picture of the tumor and, thus, enhances more precise clinical decisions ( 5 , 77 ). Indeed, a number of studies successfully consolidate the significance of LB in BC ( 78 – 81 ) and other cancers too ( 82 , 83 ).…”

“…Millions of women are diagnosed with BC and over half a million deaths are reported annually ( 3 , 4 ). There are four main molecular subtypes of BC– luminal A, luminal B, human epidermal growth factor receptor 2 (Her2)-enriched, and basal-like ( 5 ). The first two subtypes usually have a more favorable prognosis.…”

“…Breast cancer (BC) is the most malignant and emergent tumor among women cancer patients (1,2). Millions of women are diagnosed with BC and over half a million deaths are reported annually (3,4). There are four main molecular subtypes of BC-luminal A, luminal B, human epidermal growth factor receptor 2 (Her2)-enriched, and basal-like (5).…”