Table 2.

Surrogate definitions of intrinsic subtypes of breast cancer (4, 7)

Intrinsic Subtype (1)	Clinico-pathologic definition	Notes
Luminal A	‘Luminal A’	This cut-point for Ki-67 labelling index was established by comparison with PAM50 intrinsic subtyping (7). Local quality control of Ki-67 staining is important.
	ER and/or PgR positive(76)
	HER2 negative (77)
	Ki-67 low (<14%)*
Luminal B**	‘Luminal B (HER2 negative)’	Genes indicative of higher proliferation are markers of poor prognosis in multiple genetic assays (78). If reliable Ki-67 measurement is not available, some alternative assessment of tumor proliferation such as grade may be used to distinguish between ‘Luminal A’ and ‘Luminal B (HER2 negative)’.
	ER and/or PgR positive
	HER2 negative
	Ki-67 high
	‘Luminal B (HER2 positive)’	Both endocrine and anti-HER2 therapy may be indicated.
	ER and/or PgR positive
	Any Ki-67
	HER2 over-expressed or amplified
Erb-B2 overexpression	‘HER2 positive (non luminal)’
	HER2 over-expressed or amplified
	ER and PgR absent
‘Basal-like’	‘Triple negative (ductal)’	Approximately 80% overlap between ‘triple negative’ and intrinsic ‘basal-like’ subtype but ‘triple negative’ also includes some special histological types such as (typical) medullary and adenoid cystic carcinoma with low risks of distant recurrence.
	ER and PgR absent
	HER2 negative
		Staining for basal keratins (79) although shown to aid selection of true basal-like tumors, is considered insufficiently reproducible for general use.

^*This cut-point is derived from comparison with gene array data as a prognostic factor [7]. Optimal cut-points in Ki-67 labelling index for prediction of efficacy of endocrine or cytotoxic therapy may vary.

^**Some cases over-express both luminal and HER2 genes.