Oncotype DX

Analysis of clinical trials that included patients with node positive and node negative breast cancer, a recurrence score appeared to be an independent prognostic factor for local recurrence rate among those who receives whole breast radiotherapy in those on the web mastectomy without postmastectomy radio therapy.

The assay also assesses the benefit from chemotherapy.

Predicts the rate of distant recurrence in patients with early stage, ER positive, lymph node negative breast cancer.

Performed on fixed tissue on core or surgical biopsy specimen.

The assay used information from the randomized trial known as the National Surgical Adjutant Breast and Bowel Project Study B-20 which compared combinations of chemotherapy with six cycles cyclophosphamide, methotrexate, and 5-FU, plus tamoxifen hormonal therapy, with hormonal therapy alone in 651 women with lymph node negative ER positive breast cancer.

Node negative ER positive breast cancer patients with a RS of less than 18 are characterized as low risk, with over 90% of patients alive and 10 years.

Scores ranging from 0-100 and are divided into 3 risk groups.

Patients with RS score of 18 to less than 31 are classified as intermediate risk.

Patients with an RS of 31 or higher are considered as high risk of recurrence.

The test changes more than 30% of treatment decisions in node negative patients.

Rate of distant recurrence rate in node negative patients at 10 years for low risk recurrence scores 6.8%, for intermediate risk 14.3%, and 30.5% for high risk recurrence score.

Approximately 50% of lymph node negative, ER positive patients are at low risk.

The intermediate risk group is approximately 38-40% in previous studies.

Low recurrence score and intermediate scores in node negative patients in NSABP-B 20 study predicted little to no benefit from chemotherapy, while it resulted in large benefits (28%) from chemotherapy.

In the TransATAC study the rate of distant recurrence increases with the number of positive nodes for all recurrence score values.

In the above study the 9 year risk of distant recurrence for node negative patients and those with 1-3 positive nodes is similar for those with low recurrence scores.

The 9 year risk of distant recurrence increases with the number of positive nodes and the recurrence score result.

The recurrence score predicts the magnitude of chemotherapy benefit for node positive patients in the SWOG 8814 study such that low recurrence score resulted in little or no benefit from chemotherapy compared to hormonal therapy alone.

In this SWOG 8814 study a high recurrence score for patients with positive nodes resulted in a large benefit from adjuvant chemotherapy of 19% vs hormone therapy alone.

Patients with low-grade tumors can have a high recurrence score results, and patients with high-grade tumors can have low recurrence score results.

In the National Surgical Adjuvant Breast and Bowel Project B20 study 51% had low recurrence scores.

In the above study patients with high scores, likely due to luminal B tumors and most likely to benefit from adjuvant chemotherapy, and have lower ER expression, and higher expression of proliferation genes

Oncotype DX colon cancer assay is a valid independent predictor of individualized recurrence risk for stage II colon cancer.

Assay includes genes related to proliferation-Ki-67, STK15, survivin, cyclin B1, MYBL2, invasion-stromelysin 3, cathepsin L2, SCUBE 2, as well as GSTM1, CD68, BAG1 and reference genes beta actin, GAPDH, RPLPO, GUS and TFRC.

Adjuvant chemotherapy trials have found that the benefit adjuvant chemotherapy is most clearly shown in a subset of patients with tumors are measured to have a high recurrence score.

TailoRx trial demonstrated about 70% of patients with hormone receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative, axillary node–negative early-stage breast cancer, who received intermediate score on the Oncotype Dx test, could be spared chemotherapy.

The trial found no difference in the disease-free survival whether these women were treated with endocrine therapy alone or with the combination of endocrine therapy with chemotherapy.

The trial found about half of all breast cancers are hormone receptor positive, HER2 negative, and axillary node negative but up to 30% of patients have recurrences by 10 years,

This population can be spared an estimated 70% of patients and limit chemotherapy to the 30% who may benefit from it.

Adjuvant chemotherapy in the above patients reduced the risk for relapse, but the absolute benefit was only 3% to 5%,suggesting many women are being overtreated, because endocrine therapy would be adequate.

In women with hormone receptor positive HER2 negative early breast cancer, the 21-gene recurrence score essay provides prognostic information that is independent of the clinical pathological features and a high score indicates a higher rate of distant recurrence and is predictive of chemotherapy benefit.

For patients older than 50 years and whose tumors have Oncotype Dx Recurrent score is less than 26 and for patients 50 years of age or younger whose tumors have Oncotype DX with recurrence scores of less than 16, there is little to no benefit from chemotherapy.

For patients 50 years old or younger with Oncotype DX scores of 16-25, clinicians may offer chemo-endocrine therapy.

Patients with Oncotype DX with recurrence score greater than 30 should be considered a candidate for chemo and endocrine therapy.