Classic and New Markers in Diagnostics and Classification of Breast Cancer

Abstract

Breast cancer remains the most frequently diagnosed form of female’s cancer, and in recent years it has become the most common cause of cancer death in women worldwide. Like many other tumours, breast cancer is a histologically and biologically heterogeneous disease. In recent years, considerable progress has been made in diagnosis, subtyping, and complex treatment of breast cancer with the aim of providing best suited tumour-specific personalized therapy. Traditional methods for breast cancer diagnosis include mammography, MRI, biopsy and histological analysis of tumour tissue in order to determine classical markers such as estrogen and progesterone receptors (ER, PR), cytokeratins (CK5/6, CK14, C19), proliferation index (Ki67) and human epidermal growth factor type 2 receptor (HER2). In recent years, these methods have been supplemented by modern molecular methodologies such as next-generation sequencing, microRNA, in situ hybridization, and RT-qPCR to identify novel molecular biomarkers. MicroRNAs (miR-10b, miR-125b, miR145, miR-21, miR-155, mir-30, let-7, miR-25-3p), altered DNA methylation and mutations of specific genes (p16, BRCA1, RASSF1A, APC, GSTP1), circular RNA (hsa_circ_0072309, hsa_circRNA_0001785), circulating DNA and tumour cells, altered levels of specific proteins (apolipoprotein C-I), lipids, gene polymorphisms or nanoparticle enhanced imaging, all these are promising diagnostic and prognostic tools to disclose any specific features from the multifaceted nature of breast cancer to prepare best suited individualized therapy.

A new prognostic model including immune biomarkers, genomic proliferation tumor markers (AURKA and MYBL2) and clinical-pathological features optimizes prognosis in neoadjuvant breast cancer patients

“…AURKA was chosen as a proliferation gene based on this study and others already discussed in the introduction ( 23 , 24 , 64 ). As we mentioned previously, MYBL2 is one of the proliferation genes included in Oncotype, PAM50 and MammaPrint tests ( 19 ). Finally, MKI67 was chosen since Ki67 is used in the clinical setting to identify luminal B cases and the correlation between Ki67 and MKI67 has been previously established ( 65 ).…”

Comprehensive analysis of the exosomal circRNA‐miRNA‐mRNA network in breast cancer

“…Although having a relatively better prognosis, patients with breast cancer suffer a certain risk of cancer recurrence and metastasis 2 . circRNA, a novel non‐coding RNA, has been widely determined to participate into tumor progression and metastasis and could severe as potential novel biomarkers in cancer 17 . Although the functions and molecular mechanisms of circRNAs in cancer remain largely unknown, the role of miRNA sponge of circRNAs and the circRNA‐miRNA‐mRNA axis were one of the most important parts 18,19 .…”

“…2 circRNA, a novel non-coding RNA, has been widely determined to participate into tumor progression and metastasis and could severe as potential novel biomarkers in cancer. 17 Although the functions and molecular mechanisms of circRNAs in cancer remain largely unknown, the role of miRNA sponge of circRNAs and the circRNA-miRNA-mRNA axis were one of the most important parts. 18,19 cir-cRNAs have also been found in exosomes and could be transferred between different cells via exosomes to realize their functions.…”

Proteomics-Based Identification of Dysregulated Proteins and Biomarker Discovery in Invasive Ductal Carcinoma, the Most Common Breast Cancer Subtype

“…IDC refers to the neoplastic proliferation and microinvasion of luminal epithelial cells into surrounding breast stroma, by passage through the ductal wall [ 5 ], following the disruption of the ductal basement membrane and myoepithelial cell layer. Based on the histological proprieties of tumors, several subtypes of IDC have been described [ 28 ]: the classical nonspecific subtype/not otherwise specified subtype (IDC-NST/IDC-NOS) [ 5 ], breast invasive apocrine carcinoma (BAC) [ 29 ], medullary carcinoma of the breast (MBC) [ 30 ], mucinous carcinoma/colloid carcinoma (MCB) [ 31 ], invasive papillary carcinoma (IPC), invasive micropapillary carcinoma (IMPC), and tubular ductal carcinoma (TC). Synthetically, IDCs can be classified as ”no special type” because these tumors do not emphasize sufficient morphological characteristics to be classified as a distinct histological type, and ”special type” that present specific cellular and molecular landscapes [ 32 ].…”