Oncotype Dx® Predicts Chemotherapy Benefit in Node-positive Breast Cancer

Researchers affiliated with The Breast Cancer Intergroup of North America have reported that the Oncotype Dx® test identifies a subset of women with node-positive, hormone receptor-positive breast cancer who do not appear to benefit from adjuvant anthracycline-based chemotherapy. The details of this retrospective analysis of a randomized trial were presented at the 2009 San Antonio Breast Cancer Symposium and were also published early online on December 19, 2009 in Lancet Oncology.

Oncotype Dx is a genomic test that previously has been shown to predict the likelihood of cancer recurrence in women with early-stage, estrogen receptor-positive breast cancer that is treated with hormonal therapy. Women with a low risk of recurrence derive little benefit from chemotherapy. Oncotype Dx evaluates 21 genes from a sample of the patient’s cancer to determine the patient’s Recurrence Score. The Recurrence Score ranges from 0 to 100, with a higher score indicating a greater risk of recurrence. Oncotype Dx has been added to U.S. medical guidelines for early-stage breast cancer.

Oncotype Dx was initially validated among women with node-negative breast cancer, but the test also appears to provide important information about women with node-positive breast cancer. To further assess the test among women with node-positive, hormone receptor-positive breast cancer, researchers evaluated information from 367 patients. One-hundred forty-eight patients received adjuvant therapy with tamoxifen [Nolvadex®] alone (T), and 219 received tamoxifen plus cyclophosphamide, doxorubicin and 5-FU (CAF-T). Patients were divided into groups based on nodal status (1-3 or 4+T).

* Statistically significant breast cancer specific survival (BCSS) was not observed in CAF-T treated patients with low (<18)>31) Recurrence Score.
* The 10-year BCSSs were 92% for T and 87% for CAF-T for women with a low Recurrence Score.
* The 10-year BCSSs were 70% for T and 81% for CAF-T for women with an intermediate Recurrence Score.
* The 10-year BCSSs were 54% for T and 73% for CAF-T for women with a high Recurrence Score.
* These results were similar for women with one three or four or more positive lymph nodes.

Comments: These results suggest that anthracycline-based chemotherapy may not benefit women with node-positive, hormone receptor-positive breast cancer and a low Oncotype Dx Recurrence Score. For patients with an intermediate Recurrence Score, the trend was for a benefit from CAF. A prospective study is proposed to confirm these findings. In addition, currently used taxane-based adjuvant regimens may yield the same results as CAF.

References:

Albain KS, Barlow WE, Shak S et al. Prediction of 10-year chemotherapy benefit and breast cancer-specific survival by the 21-gene Recurrence Score (RS) assay in node-positive, ER-positive breast cancer—An update of SWOG-8814 (INT0100). Presented at the 32nd CTRC-AACR San Antonio Breast Cancer Symposium. December 9-13, 2009. San Antonio, TX. Abstract 112.

Albain KS, Barlow WE, Shak S et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised clinical trial. Lancet Oncology [early online publication].