Table 2.

Commercially available prognostic multi-gene signatures for breast cancer patients [6,54]

	MammaPrint [43,44]	Veridex 76-gene [44]	MapQuant Dx [45]	MapQuant Dx simplified [46]	Oncotype DX [30,47]	Theros [48,49]
Technique	DNA microarray	DNA microarray	DNA microarray	qRT-PCR	qRT-PCR	qRT-PCR
Provider	Agendia	Currently not commercially available	Ipsogen	Ipsogen	Genomic Health	bioTheranostics
Assay type	70-gene signiture	76-gene signiture	97-gene signiture	8-gene signature	21-gene recurrence score	2-gene ratio of HOXB13 to IL17R (H/l)/molecular grade index
Tissue type	Fresh or frozen	Fresh or Frozen	Fresh or Frozen	FFPE	FFPE	FFPE
Discovery set	78 ER±, N0, < 5 cm diameter cancers, age < 55 years	115 ER±, N0 cancers	64 ER+ cancers	64 ER+ cancers	447 ER+ samples, including samples from the tamoxifen only group of the NSABP B-20 trial	60 ER+ tumors, tamoxifen only treated patients 20 microdissected FFPE samples
Initial validation set	295 ER±, N±, < 5 cm diameter cancer, age < 52 years	171 ER±, N0 cancers	597 ER± cancers, of which 125 profiled in-house	597 ER± cancers, of which 125 profiled in-house	668 ER+ samples from NSABP B-14trial90 (tamoxifen-treated)	20 ER+ FFPE samples
Outcome	Distant metastasis at 5 years	Distant metastasis at 5 years	Good (GG II) or poor (GG I III) prognosis	Good (GG II) or poor (GG I III) prognosis	Disease-free relapse at 10 years	Relapse-free and overall survival
Clinical application	To aid in prognostic prediction in patients < 61 year of age with stage I or II, N0 disease with a tumor size of ≤ 5 cm	To prognose N0 patients	To restratify grade 2 tumors into low-risk grade 1 or high-risk grade 3 tumors, specifically for invasive, primary, ER+ grade 2 tumors	To restratify grade 2 tumors into low-risk grade 1 or high-risk grade 3 tumors, specifically for invasive, primary, ER+ grade 2 tumors	To predict the risk of recurrence in patients with ER+, N0 disease treated with tamoxifen; to identify patients with a low risk of recurrence who may not need adjuvant chemotherapy	To stratify ER+ patients into groups with a predicted low-risk or high-risk of recurrence and a predicted good or poor response to endocrine therapy
Resulets presentation	Dichotomous; good or poor prognosis	Dichotomous; good or poor prognosis	Dichotomous, GGII or GG I III	Dichotomous, GGII or GG I III	Continuous variable; recurrence score	Continuous variable; risk of recurrence score
Additional information provided	mRNA levels of ER, PR, and HER2 (Targetprint); Intrinsic subtypes (Blueprint)	-	-	-	mRNA levels of ER, PR, and HER2	Molecular grade index
Prognostic value in other populations	Up to 3 positive nodes, and HER2+ disease	ER+, N0 patients treated with tamoxifen	ER+, receiving aromatase inhibitors	ER+, receiving aromatase inhibitors	ER+ and 1-3 N+, ER+ postmenopausal receiving aromatase inhibitors	-
Predictive value	Chemotherapy response (poor prognosis group)	Chemotherapy response (poor prognosis group)	Chemotherapy response (GG I III)	Chemotherapy response (GG I III)	Chemotherapy response (high recurrence score)	Chemotherapy response (high risk of recurrence score)*
Level of evidence	II	III	III	III	I	III
FDA approval	Yes	No	No	No	No	No
Availability	Europe and USA		Europe	Europe	Europe and USA	USA

FDA: US Food and Drug Administration; MGI: molecular grade index; GGI: genomic grade index; FFPE: formalin-fixed paraffin-embedded; ER: oestrogen receptor; PR: progesterone receptor; N: lymph nodes; ±: positive and negative; +: positive.

^*based on indirect evidence.