The breast cancer genome - a key for better oncology

The diversity of breast cancer has been acknowledged for decades, but recent technological advances in molecular biology have given detailed knowledge on how extensive this heterogeneity really is. Traditional classification based on morphology has given limited clinical value; mostly because the majority of breast carcinomas are classified as invasive ductal carcinomas, which show a highly variable response to therapy and outcome [1]. The first molecular sub-classification with a major impact on breast cancer research was proposed by Perou and colleagues where the tumors were subdivided according to their pattern of gene expression [2,3]. Five groups were identified and named Luminal A, Luminal B, Basal-like, Normal-like and the HER-2-enriched subgroups. These intrinsic subgroups have been shown to be different in terms of biology, survival and recurrence rate [3,4]. The molecular subgroups have been extended to also include a sixth subgroup which has been named the claudin- low group, based on its low expression level of tight junction genes (the claudin genes) [5]. Different methods for the assignment of individual tumors to its molecular subgroup is proposed; each based on the expression levels of different sets of genes [4,6,7]. The agreement between methods on how to classify individual tumors are not optimal and how to establish more robust single sample predictors is actively debated [8-11].Aneuploidy is the presence of an abnormal number of parts of or whole chromosomes and is one feature that clearly separates cancer cells from normal cells. This was proposed as being important in cancer nearly a century ago by Theodor Boveri [12]. With array-based comparative genomic hybridization (aCGH) a genome wide profile of the copy number alterations in the tumor can be obtained. These patterns are related to the molecular subtypes with distinct differences in the number of alterations between the subtypes [13-16]. These copy number alterations (CNAs) alter the dosa