Table 3. the association of histological grades sub-classification and intrinsic subtypes.

A) TCGA cohort	LGG		HGG
Intrinsic Subtypes	HG1	HG1-like	HG3-like	HG3
Normal-like	0 (0%)	0 (0%)	0 (0%)	5 (2.8%)
Luminal-A	27 (87.1%)	92 (91.1%)	21 (26.9%)	33 (18.6%)
Luminal-B	4 (12.9%)	8 (7.9%)	32 (41%)	62 (35%)
Basal-like	0 (0%)	0 (0%)	8 (10.3%)	42 (23.7%)
ERBB2+	0 (0%)	1 (1%)	17 (21.8%)	35 (19.8%)
Total	31 (100%)	101 (100%)	78 (100%)	177 (100%)
			Chi-square test of homogeneity within HG3-like and HG3 tumors p-value = 0.06
	Chi-square test of independence between LGG and HGG tumors versus Normal-like, Luminal A as one class and Luminal B, Basal-like, HER2-enriched tumors as another class p-value = 4.281E-39

B) Uppsala and Stockholm cohorts	LGG		HGG
Intrinsic Subtypes	HG1	HG1-like	HG3-like	HG3
Normal-Like	41 (37.3%)	43 (33.1%)	3 (5.6%)	1 (1%)
No Subtype	13 (11.8%)	23 (17.7%)	4 (7.4%)	1 (1%)
Luminal-A	43 (39.1%)	50 (38.5%)	12 (22.2%)	10 (9.9%)
Luminal-B	4 (3.6%)	6 (4.6%)	15 (27.8%)	27 (26.7%)
ERBB2+	6 (5.5%)	7 (5.4%)	9 (16.7%)	20 (19.8%)
Basal-like	3 (2.7%)	1 (0.8%)	11 (20.4%)	42 (41.6%)
Total	110 (100%)	130 (100%)	54 (100%)	101 (100%)
	Chi-square test of homogeneity within HG1-like and HG1 tumors p-value = 0.43		Chi-square test of homogeneity within HG3-like and HG3 tumors p-value = 0.25
	Chi-square test of independence between LGG and HGG tumors versus Normal-like, Luminal-A as one class and Luminal-B, Basal-like, HER2-enriched tumors as another class p-value = 2.8e-45

Breast cancer intrinsic subtype stratification according to histological and genetic grade classification of TCGA A. Uppsala, and Stockholm B. Breast cancer cohorts:Low-genetic grade LGG (HG1+HG1-like) and high-genetic grade HGG (HG3-like+HG3) are considered two major genetically distinct classes of BC.