@entity513 ( @entity513 ) is a major histo-morphologic type of @entity0 . Histological grading (HG) of @entity513 is widely adopted by oncologists as a prognostic factor. However, HG evaluation is highly subjective with only 50%-85% inter-observer agreements. Specifically, the subjectivity in the assignment of the intermediate grade (histologic grade 2, @entity17484 ) @entity0 (comprising ~50% of @entity513 cases) results in uncertain disease outcome prediction and sub-optimal systemic therapy. Despite several attempts to identify the mechanisms underlying the HG classification, their molecular bases are poorly understood.We performed integrative bioinformatics analysis of TCGA and several other cohorts (total 1246 @entity1 ). We identified a 22-gene @entity5 @entity146 grading classifier (22g-TAG) that reflects global bifurcation in the @entity513 transcriptomes and reclassified @entity1 with @entity17484 @entity5 into two genetically and clinically distinct subclasses: histological grade 1-like ( @entity17485 -like) and histological grade 3-like ( @entity17486 -like). The expression profiles and clinical outcomes of these subclasses were similar to the @entity17485 and @entity17486 @entity5 , respectively. We further reclassified @entity513 into low genetic grade (LGG = @entity17485 + @entity17485 -like) and high genetic grade (HGG = @entity17486 ) subclasses. For the @entity17485 -like and @entity17486 -like IDCs we found subclass-specific DNA alterations, somatic mutations, oncogenic pathways, cell cycle/mitosis and stem cell-like expression signatures that discriminate between these @entity5 . We found similar molecular patterns in the LGG and HGG @entity5 classes respectively.Our results suggest the existence of two genetically-predefined @entity513 classes, LGG and HGG, driven by distinct oncogenic pathways. They provide novel prognostic and therapeutic biomarkers and could open unique opportunities for personalized systemic therapies of @entity513 @entity1 .

Genome and transcriptome delineation of two major oncogenic pathways governing invasive XXXX development.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity0 :: ('MESH:D001943', 'Disease') :: ['breast cancers', 'breast cancer'] @entity146 :: ('MESH:D001523', 'Disease') :: ['aggressiveness'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity513 :: ('MESH:D044584', 'Disease') :: ['IDC', 'Invasive ductal carcinoma'] @entity17484 :: ('283955', 'Gene') :: ['HG2'] @entity17486 :: ('339039', 'Gene') :: ['HG3', 'HG3-like+HG3'] @entity17485 :: ('339044', 'Gene') :: ['HG1']
@entity0 :: (MESH:D001943,Disease) :: ['ductal breast cancer']
