Clinical relevance of the triple-negative breast cancer concept: genetic basis and clinical utility of the concept

Abstract

The beginning of microarray technology in the 1990s and the sequencing of the human genome in 2000 paved the way for the seminal paper of the Stanford group on the molecular portraits of human breast tumours in the same year. They described four distinct breast cancer subtypes, which they called 'luminal', 'basal', 'HER2-positive', and 'normal breast-like', based on unique gene expression patterns. This paper caused a paradigm shift. Breast cancer was no longer hormone receptor-positive or -negative, but rather luminal, basal or HER2-positive. Since then, numerous papers have appeared, trying to further characterise these subtypes on the DNA, RNA and protein level. Other groups have focussed on the epidemiology, prognosis and outcome after therapy of breast cancer patients according to these molecular subtypes. A promising prognostic marker within the subgroup of basal-like breast cancer is an up-regulated immune response, which is associated with favourable outcome. In addition, the majority of basal-like breast cancers harbour traits of a DNA damage repair defect. This feature can be exploited by the use of DNA damaging agents, and first exciting clinical results of the combination of carboplatin, gemcitabine and a poly (ADP-ribose) polymerase 1 (PARP-1) inhibitor have recently been reported. In this review, the molecular characterisation of triple-negative breast cancer, a proxy for basal-like breast cancer, is described and findings have been put into clinical context.