18 Given these observations, we propose here that RB/p16 dysfunction in TNBCs reflects a biologically meaningful subtype of TNBCs, and that a key event in promoting the development of this phenotype is inactivation of the BRCA1 gene.
The data on the association of insomnia with hypertension and diabetes, as well as previous reports on insomnia and the stress system (6– 8) and the autonomic system (9– 11), provide the basis for a meaningful subtyping of chronic insomnia based on objective duration of sleep.
Conventional research into survivalness has focused on individual tumour types, wherein cancer patients of the same type are first stratified into subtypes according to genomic data (mostly expression data [ 5– 9], and now mutation data [ 10]), and then are correlated with survival data in the hope of discovering clinically meaningful subtypes.
In our opinion, MMP-9 expression could help segregate subsets of aggressive breast cancer into clinically meaningful subtypes.
Cancers can also be divided into clinically meaningful subtypes based on their gene expression patterns that may be indicative of response to a treatment, like Her2 positive breast cancers [ 4] or KIT positive gastro-intestinal tumours [ 5], for example.
A GES list including most of relevant biological pathways in breast cancer will certainly help to gain more insight into biological systems involved in this disease and will provide a framework to develop rational therapeutic strategies based on meaningful subtyping.
An evaluation of subtypes of stroke was not very meaningful because, before the 1990s, differential diagnosis was often not done, resulting in many cases being classified as stroke, not otherwise specified.
The increasing complexity of lymphoma diagnosis and classification is the result of a vastly improved understanding of its underlying molecular pathogenesis and resultant attempts to group subtypes of lymphoma in a clinically and biologically meaningful manner.
The survival of patients with metastatic or recurrent TNBC remains poor to date, due to lack of meaningful biologic targets, and the recurrence rate is higher than other subtypes of breast cancers when compared at same stage of disease.
