Kathy Albain, MD
Patients with hormone receptor (HR)–positive, HER2-negative breast cancer who have a favorable gene-expression profile may be able to avert chemotherapy and receive endocrine treatment alone, according to a prospective validation study of a gene expression assay recently published in The New England Journal of Medicine
The international, multicenter prospective analysis of the TAILORx study validated the clinical benefit of a 21-gene expression assay, the Oncotype DX Recurrence Score, in 10,253 women with HR-positive, HER2-negative axillary node-negative invasive breast cancer.
On the assay, tumor recurrence scores range from 0 to 100, with higher scores indicating a greater risk of recurrence. Patients with a score of 0 to 10 (n = 1629) were assigned to receive endocrine therapy alone, while those with a score of 26 or higher were assigned to receive chemotherapy plus endocrine therapy (n = 1736). Patients with a score of 11 to 25 were assigned to receive chemotherapy plus endocrine therapy or endocrine therapy alone (n = 6907), since the benefits of chemotherapy were uncertain in this group.
In patients who received endocrine therapy without chemotherapy and had a recurrence score between 0 and 10, the rate of invasive disease-free survival at 5 years was 93.8% (95% CI, 92.4-94.9). The rate of freedom from recurrence of breast cancer at a distant site at 5 years was 99.3% (95% CI, 98.7-99.6), the rate of freedom from recurrence at 5 years was 98.7% (95% CI, 97.9-99.2), and the rate of overall survival at 5 years was 98.0% (95% CI, 97.1-98.6). There were 88 events of either invasive cancer or death and 30 deaths reported in this subgroup.
“This should provide a lot of reassurance to women and their physicians,” Kathy Albain, MD, 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.”
The primary endpoints were time-to-event analysis of the rate of survival free from invasive disease, defined as the first event of recurrence of ipsilateral breast tumor, local recurrence, regional recurrence, distant recurrence, contralateral second primary invasive cancer, second primary nonbreast invasive cancer, or death without evidence of recurrence. Secondary endpoints included time-to-event analyses of the freedom from the recurrence of breast cancer at a distant site, freedom from any recurrence, and overall survival rate.
Patients had to meet NCCN guidelines for the recommendation of adjuvant chemotherapy, including a primary tumor size of 1.1 to 5.0 centimeters in the greatest dimension for a tumor of any grade, or a size of 0.6 to 1.0 centimeters in the greatest dimension for a tumor of intermediate or high histologic grade or nuclear grade, or both. Additional necessary criteria included an ECOG performance-status score of 0 or 1 and normal hematologic, bone marrow, hepatic, renal, pulmonary, and cardiac function. Patients with HER2-overexpressing disease were excluded, due to a high rate of recurrence and a likely benefit from adjuvant HER2-directed therapy plus chemotherapy.
Despite the lymph nodes not being involved in this study, the tumors had features that met established guidelines for consideration of adjuvant chemotherapy, followed by tamoxifen or another endocrine therapy, the authors noted.
Previous studies have demonstrated that patients with estrogen receptor¬–positive disease would be overtreated with the addition of chemotherapy, and that the widespread use of adjuvant chemotherapy has contributed to the declining breast-cancer mortality, the authors wrote.
Moreover, earlier 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.
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.
Sparano J, Gray R, Makower D, et al. Prospective validation of a 21-gene expression assay in breast cancer [published online September 27, 2015]. N Engl J Med. doi: 10.1056/NEJMoa1510764.