Triple-negative breast cancer is a heterogeneous disease and specific therapies have
not been available for a long time. Therefore, conventional chemotherapy is still
considered the clinical state of the art. Different subgroups of triple-negative breast
cancer have been identified on the basis of protein expression, mRNA signatures, and
genomic alterations. Important elements of triple-negative breast cancer biology include
high proliferative activity, an increased immunological infiltrate, a basal-like and
a mesenchymal phenotype, and deficiency in homologous recombination, which is in part
associated with loss of BRCA1 or BRCA2 function. A minority of triple-negative tumours
express luminal markers, such as androgen receptors, and have a lower proliferative
activity. These biological subgroups are overlapping and currently cannot be combined
into a unified model of triple-negative breast cancer biology. Nevertheless, the molecular
analysis of this disease has identified potential options for targeted therapeutic
intervention. This has led to promising clinical strategies, including modified chemotherapy
approaches targeting the DNA damage response, angiogenesis inhibitors, immune checkpoint
inhibitors, or even anti-androgens, all of which are being evaluated in phase 1-3
clinical studies. This Series paper focuses on the most relevant clinical questions,
summarises the results of recent clinical trials, and gives an overview of ongoing
studies and trial concepts that will lead to a more refined therapy for this tumour
type.