Biological subtypes of breast cancer: Prognostic and therapeutic implications

Table 1 2013 St. Gallen - intrinsic subtypes of breast cancer

Intrinsic subtype	Clinicopathological surrogate definition
Luminal-A	“Luminal-A-like” all of: ER and PgR positive HER2 negative Ki-67 “low”a Recurrence risk “low” based on multi-gene-expression assay (if available) b	a A level of < 14% best correlated with the gene-expression definition of Luminal A based on the results in a single reference laboratoryb PgR cut-point of ≥ 20% to best correspond to Luminal A subtype
Luminal-B	Luminal-B-like (HER 2 positive) ER positive HER2 negative and at least one of: Ki-67 “high” PgR “negative or low” Recurrence risk “high” based on multi- gene-expression assay (if available)  Luminal-B (HER 2 negative) ER positive HER2 over-expressed or amplified Any Ki-67 Any PgR
Erb-B2 overexpression	HER 2 positive (non-luminal) HER2 over-expressed or amplified ER and PgR absent
Basal-like	Triple negative (ductal) ER and PgR absent HER2 negative	There is an 80% overlap between “triple-negative” and intrinsic “basal-like” subtype

Table 2 First generation gene expression signatures

Gene signature	MammaPrint	OncotypeDX	MapQuantDX	Breast cancer ındex	PAM 50 assay
Starting material	FF or stabilized RNA, FFPE	FFPE	FFPE, FF	FFPE	FFPE
Analytical platform	Microarray, RT-PCR	qRT-PCR	Microarray, qRT-PCR	qRT-PCR	nCounter
Number of genes	70	21	97/9	7	50
Indications	Stage I/II, 5 cm, ER (+), Node (-)/[1-3 Node (+)]	ER(+), Node (-)	ER (+), G2	ER (+)	All, Node (-) untreated
Application	Clinical outcome	Clinical outcome, benefit from chemotherapy	Molecular grading prediction of response to TMX	Clinical outcome, prediction of response to TMX	Subtype definition, risk of relapse without treatment
FDA approved	Yes	No	No	No	No
ASCO and NCCN recommendation	No	Yes	No	No	No

FF: Fresh frozen; FFPE: Formalin fixed paraffin embedded; G: Grade; TMX: Tamoxifen.