World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website http://www.wjon.org

Review

Volume 8, Number 2, April 2017, pages 34-40

The Era of Multigene Panels Comes? The Clinical Utility of Oncotype DX and MammaPrint

**Table 1.** Key Studies of Clinical Evidence to the Oncotype DX [3, 5-13]
Study	Prospective trial	Reported by	N	Patient population	Treatment	End point	Result
NSABP B-14 [3]	Yes	Paik et al	668	HR⁺, node-negative	TAM	10-year distant recurrence/secondary end point: RS and risk of distant recurrence	The rates of 10-year distant recurrence were 6.8%, 14.3% and 30.5% in low-risk, intermediate-risk and high-risk group.
WGS Plan B [10]	Yes	Gluz et al	3,198	HR⁺, 41.1% node-positive	Endocrine therapy and chemotherapy, endocrine alone if RS ≤ 11	DFS	The 3-year DFS is quiet low in patients omitted with chemotherapy with RS ≤ 11.
PACS 01 trial [9]	Yes	Penault-Llorca et al	530	HR⁺, node-positive	FEC for six cycles or FEC for three cycles followed by docetaxel for three cycles	DRFI/second end point: DFS and OS	The 5-year DRFI of low risk of RS is 93.7% versus 87.3% and 69.3% in intermediate or high RS (P < 0.001). The 21-gene RS maintains significant prognostic impact in HR⁺, node-positive pts who have received FEC or FEC-D adjuvant chemotherapy.
TAILORx [6]	Yes	Sparano et al	1,626	HR⁺, HER2^-, node-negative, cT1cT2 or cT1b with high tumor grade	Endocrine therapy (TAM or anastrozole)	DFS/secondary end point: DDFS,OS	Among patients with tumors that had a favorable gene-expression panel had very low rates of recurrence at 5 years with endocrine therapy alone.
NSABP B-20 [5]	Yes	Paik et al	651	ER⁺, node-negative	TAM or TAM plus chemotherapy	DFS	Patients with high-RS tumors had a large benefit from chemotherapy, 10-year distant recurrence rate decreased by 27.6%. Patients with low-RS tumors derived minimal benefit from chemotherapy.
SWOG-8814 [7]	Retrospective analysis for RS	Albain et al	367	HR⁺, node-positive	TAM or CAF followed by TAM	DFS/OS	There was no benefit of CAF in patients with a low recurrence score (score < 18; P = 0.97), but an improvement in disease-free survival for those with a high recurrence score (score ≥ 31; P = 0.033), after adjustment for number of positive nodes.
ECOG E2197 [12]	Yes	Esteva et al	465	HR⁺, 0 - 3 node-positive	AC for four cycles or TA for cycles	Recurrence free interval (RFI)	RS was a highly significant predictor of recurrence. The 5-year recurrence rate was less than 5% or for the estimated 46% of patients who have a low RS (< 18).
TranATAC [13]	Yes	Dowsett et al	1,071	HR⁺, postmenopausal women	Endocrine therapy: tamoxifen, anastrozole or combination	Distant recurrence free survival/OS	The 9-year DR rates in low, intermediate, and high RS groups were 4%, 12%, and 25% in N0 patients; 17%, 28%, and 49%, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients.
NSABP B-28 [8]	Yes	Solin et al	1,065	ER⁺, operable breast cancer node-positive	AC × 4 or AC × 4 followed by paclitaxel × 4 endocrine therapy	LRR as first event, DFS, OS	The 10-year LRR for low, intermediate, high RS is 3.3%, 7.2% and 12.2%. RS statistically significantly predict risk of LRR in node-positive, ER-positive breast cancer patients after chemotherapy and endocrine therapy.
RxPONDER [11]	Yes	Ramsey et al	Ongoing	HR⁺, HER2^-, 1 - 3 lymph nodes and RS ≤ 25	Endocrine therapy alone versus chemotherapy followed by endocrine therapy	DFS and cutoff point for RS value, secondary endpoint: DDFS, local disease-free interval, OS	Ongoing, intend to report in 2022.

Table 1. Key Studies of Clinical Evidence to the Oncotype DX [3, 5-13]

Study

Prospective trial

Reported by

Patient population

Treatment

End point

Result

NSABP B-14 [3]

Yes

Paik et al

668

HR⁺, node-negative

TAM

10-year distant recurrence/secondary end point: RS and risk of distant recurrence

The rates of 10-year distant recurrence were 6.8%, 14.3% and 30.5% in low-risk, intermediate-risk and high-risk group.

WGS Plan B [10]

Yes

Gluz et al

3,198

HR⁺, 41.1% node-positive

Endocrine therapy and chemotherapy, endocrine alone if RS ≤ 11

DFS

The 3-year DFS is quiet low in patients omitted with chemotherapy with RS ≤ 11.

PACS 01 trial [9]

Yes

Penault-Llorca et al

530

HR⁺, node-positive

FEC for six cycles or FEC for three cycles followed by docetaxel for three cycles

DRFI/second end point: DFS and OS

The 5-year DRFI of low risk of RS is 93.7% versus 87.3% and 69.3% in intermediate or high RS (P < 0.001).
The 21-gene RS maintains significant prognostic impact in HR⁺, node-positive pts who have received FEC or FEC-D adjuvant chemotherapy.

TAILORx [6]

Yes

Sparano et al

1,626

HR⁺, HER2^-, node-negative, cT1cT2 or cT1b with high tumor grade

Endocrine therapy (TAM or anastrozole)

DFS/secondary end point: DDFS,OS

Among patients with tumors that had a favorable gene-expression panel had very low rates of recurrence at 5 years with endocrine therapy alone.

NSABP B-20 [5]

Yes

Paik et al

651

ER⁺, node-negative

TAM or TAM plus chemotherapy

DFS

Patients with high-RS tumors had a large benefit from chemotherapy, 10-year distant recurrence rate decreased by 27.6%. Patients with low-RS tumors derived minimal benefit from chemotherapy.

SWOG-8814 [7]

Retrospective analysis for RS

Albain et al

367

HR⁺, node-positive

TAM or CAF followed by TAM

DFS/OS

There was no benefit of CAF in patients with a low recurrence score (score < 18; P = 0.97), but an improvement in disease-free survival for those with a high recurrence score (score ≥ 31; P = 0.033), after adjustment for number of positive nodes.

ECOG E2197 [12]

Yes

Esteva et al

465

HR⁺, 0 - 3 node-positive

AC for four cycles or TA for cycles

Recurrence free interval (RFI)

RS was a highly significant predictor of recurrence. The 5-year recurrence rate was less than 5% or for the estimated 46% of patients who have a low RS (< 18).

TranATAC [13]

Yes

Dowsett et al

1,071

HR⁺, postmenopausal women

Endocrine therapy: tamoxifen, anastrozole or combination

Distant recurrence free survival/OS

The 9-year DR rates in low, intermediate, and high RS groups were 4%, 12%, and 25% in N0 patients; 17%, 28%, and 49%, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients.

NSABP B-28 [8]

Yes

Solin et al

1,065

ER⁺, operable breast cancer node-positive

AC × 4 or AC × 4 followed by paclitaxel × 4 endocrine therapy

LRR as first event, DFS, OS

The 10-year LRR for low, intermediate, high RS is 3.3%, 7.2% and 12.2%. RS statistically significantly predict risk of LRR in node-positive, ER-positive breast cancer patients after chemotherapy and endocrine therapy.

RxPONDER [11]

Yes

Ramsey et al

Ongoing

HR⁺, HER2^-, 1 - 3 lymph nodes and RS ≤ 25

Endocrine therapy alone versus chemotherapy followed by endocrine therapy

DFS and cutoff point for RS value, secondary endpoint: DDFS, local disease-free interval, OS

Ongoing, intend to report in 2022.