Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer lacking hormone receptor expression and HER2 gene amplification. TNBC represents a heterogeneous subtype of breast cancer, characterized by poor prognosis, high invasiveness, high metastatic potential, and a tendency to relapse. In this review, the specific molecular subtypes and pathological aspects of triple-negative breast cancer are illustrated, with particular attention to the biomarker characteristics of TNBC, namely: regulators of cell proliferation and migration and angiogenesis, apoptosis-regulating proteins, regulators of DNA damage response, immune checkpoints, and epigenetic modifications. This paper also focuses on omics approaches to exploring TNBC, such as genomics to identify cancer-specific mutations, epigenomics to identify altered epigenetic landscapes in cancer cells, and transcriptomics to explore differential mRNA and protein expression. Moreover, updated neoadjuvant treatments for TNBC are also mentioned, underlining the role of immunotherapy and novel and targeted agents in the treatment of TNBC.

Breast cancer is clinically and biologically heterogeneous and is classified into different subtypes according to the molecular landscape of the tumor. Triple-negative breast cancer is a subtype associated with higher tumor aggressiveness, poor prognosis, and poor response to treatment. In metastatic breast cancer, approximately 6% to 10% of new breast cancer cases are initially staged IV (de novo metastatic disease). The number of metastatic recurrences is estimated to be 20–30% of all existing breast tumor cases, whereby the need to develop specific genetic markers to improve the prognosis of patients suffering from these deadly forms of breast cancer. As an alternative, liquid biopsy methods can minutely identify the molecular architecture of breast cancer, including aggressive forms, which provides new perspectives for more precise diagnosis and more effective therapeutics. This review aimed to summarize the current clinical evidence for the application of circulating tumor DNA in managing breast cancer by detailing the increased usefulness of this biomarker as a diagnostic, prognostic, monitoring, and surveillance marker for breast cancer.

Mortality rates from breast cancer in young women have fallen considerably in high-income countries but continue to rise in low-income countries such as Mo

Accurate detection of BRCA1 and BRCA2 variants is essential for breast cancer diagnosis. However, the large size of these genes poses challenges for comprehensive analysis using short-read sequencing, which is generally limited to coding regions and may miss deep intronic and structural variants. This study evaluated the performance of Oxford Nanopore long-read sequencing (ONT-LRS) for comprehensive BRCA1 and BRCA2 analysis and compared its diagnostic yield with Ion Torrent sequencing. In this retrospective study, DNA samples from 27 individuals with breast cancer were initially analysed using Ion Torrent sequencing according to standard clinical workflows. Full BRCA1 and BRCA2 genes were subsequently amplified by long-range PCR and sequenced on R10.4.1 flow cells. Variants identified by ONT-LRS were compared with those detected by Ion Torrent. High concordance was observed between ONT-LRS and Ion Torrent for exonic single-nucleotide variants. Importantly, ONT-LRS identified additional variants not detected by Ion Torrent, including a deep intronic variant predicted to alter splicing and one structural variant. This study suggest that ONT-LRS extends the diagnostic capabilities of short-read sequencing by enabling accurate detection of BRCA1 and BRCA2 deep intronic and structural variants that may otherwise be overlooked, with potential implications for patient management and family counselling.