Fig. 6. Re-definition of claudin-low as a breast cancer phenotype.

a In the established model, claudin-low is interpreted as a sixth subtype, analogous to the intrinsic subtypes. b When stratified by intrinsic subtype, claudin-low tumors, however, show characteristics associated with their intrinsic subtype. This implies that tumors are not claudin-low instead of their intrinsic subtype, rather that tumors can carry a claudin-low phenotype in addition to their intrinsic subtype. In the binary model, a tumor is either classified as claudin-low, or non-claudin-low. c The comparative analysis of CoreCL tumors and claudin-low tumors identified by the nine-cell line predictor, indicates that claudin-low may in fact be a continuous feature. Thus, individual tumors may show varying degrees of claudin-lowness, rather than simply being claudin-low or non-claudin-low. In this model, CoreCL tumors, on average, have a higher degree of claudin-lowness than claudin-low tumors identified by the nine-cell line predictor. The continuous model opens for the possibility of pure claudin-low tumors, uncoupled from the intrinsic subtypes.