Multigene Test May Avert Chemotherapy for Some Breast Cancer Patients

Women with a certain type of breast cancer whose tumors have a favorable gene-expression profile may be able to safely avoid chemotherapy without an increased risk of recurrence, a new study has found.

Kathy Albain, MD

Women with a certain type of breast cancer whose tumors have a favorable gene-expression profile may be able to safely avoid chemotherapy without an increased risk of recurrence, a new study has found.

In this international, multicenter trial, researchers examined 21 genes from a tumor sample to determine how active the genes are. The tumor was then scored between 0 and 100 using Oncotype DX; the lower the score, the lower the chance of recurrence in distant organs if treated with a hormone, such as tamoxifen.

Previous studies involving fewer participants found that low-scoring tumors suggested that chemotherapy does not work well and does not add to the survival benefit of tamoxifen.

The clinical trial (NCT00310180), published in New England Journal of Medicine, included 10,253 women with hormone-receptor positive, HER2-negative, axillary node—negative breast cancer. Despite the lymph nodes not being involved, the tumors had features that met established guidelines for consideration of adjuvant chemotherapy, followed by tamoxifen or another endocrine therapy.

Nearly 16% of the women had tumors that scored between 0 and 10 and were assigned endocrine therapy without chemotherapy. After 5 years, the rate of overall survival was 98% (95% CI, 97.1—98.6). In addition, the rate of invasive disease-free survival was 93.8% (95% CI, 92.4–94.9), rate of nonrecurrence at a distant site was 99.3% (95% CI, 98.7–99.6), and the rate of nonrecurrence at a distant or local–regional site was 98.7% (95% CI, 97.9–99.2).

Researchers concluded that these findings provide the highest level of evidence that the multigene test can spare the use of chemotherapy in women with low-scoring tumors who otherwise would have been recommended to receive chemotherapy.

“This should provide a lot of reassurance to women and their physicians,” Kathy Albain, MD, FACP, FASCO, coauthor and oncologist at Loyola University Medical Center and Loyola University Chicago Stritch School of Medicine, said in a statement. “In women whose breast cancer scored low on the multigene test, there was outstanding survival with endocrine therapy alone. The test provides us with greater certainty of who can safely avoid chemotherapy.”

Of the 10,253 women enrolled in the trial, 68% had tumors that scored midrange between 11 and 25. These women were randomly assigned to receive either hormone therapy supplemented with chemotherapy or hormone therapy alone. Follow-up is still needed to determine whether women with tumors in the intermediate-score range can safely waive chemotherapy without increasing their risk of recurrence.

The trial received support from the National Cancer Institute, the Breast Cancer Research Foundation, and Komen Foundation. The Oncotype DX Recurrence Score multigene test is made by Genomic Health, Inc.

Sparano J, Gray R, Makower D, et al. Prospective validation of a 21-gene expression assay in breast cancer [published online before print September 27, 2015]. N Engl J Med.