Most women with early-stage breast cancer can forgo chemotherapy when treatment is guided by the Oncotype DX 21-gene assay
Long-awaited results of the phase III TAILORx study show that most women with hormone receptor-positive, HER2-negative, axillary node-negative early-stage breast cancer and a mid-range score on the Oncotype DX 21-tumor gene expression assay do not need chemotherapy after surgery. The study found no improvement in disease-free survival (DFS) when chemotherapy was added to hormone therapy in this group. These findings can have a profound impact on clinical practice and can spare thousands of women the side effects of chemotherapy.
Based on evidence from several prior studies, the 21-gene expression assay (Oncotype DX recurrence score) is widely used to provide prognostic information about the risk of breast cancer recurrence within 10 years, and to predict which patients are most likely to derive a large benefit from chemotherapy. Women with a low score (0-10) typically receive only hormone therapy and those with a high score (26 or more) receive hormone therapy in combination with chemotherapy. However, before TAILORx, there was uncertainty about the best treatment for women with a mid-range score of 11-25 on the Oncotype DX breast recurrence score test.
The TAILORx trial enrolled 10,273 women with hormone receptor-positive, HER2-negative, axillary node-negative breast cancer of whom 6,711 had a mid-range recurrence score of 11-25. These patients were randomly assigned to receive hormone therapy alone or hormone therapy and chemotherapy. The primary endpoint was invasive disease-free survival (iDFS), and the trial was designed to show non-inferiority of endocrine therapy alone compared to the combined use of endocrine therapy and chemotherapy. In this study, an iDFS event was defined as a recurrence of cancer in the breast, regional lymph nodes and/or distant organs, a second primary cancer in the opposite breast or another organ, or death from any cause.
After a median follow-up of 7.5 years, the study met its primary endpoint indicating that hormone therapy alone was not less effective than chemotherapy plus hormone therapy in women with a recurrence score of 11-25 (HR[95%CI]: 1.08, 95%[0.94-1.24]; p=0.26). In addition to this, endocrine therapy alone was also non-inferior to the chemotherapy containing treatment regimen in terms of distant recurrence-free interval (HR: 1.03, p=0.80), recurrence-free interval (HR: 1.12, p=0.28), and overall survival (HR: 0.97, p=0.80). The nine-year rates were similar in the two treatment arms for disease-free survival (83.3% vs. 84.3%), distant recurrence (94.5% vs. 95.0%), and overall survival (93.9% vs. 93.8%), further illustrating the lack of benefit from adding chemotherapy to hormone therapy. TAILORx did identify a subgroup of women who do seem to have some benefit of chemotherapy: women 50 years or younger who had a breast recurrence score of 16-25 (2% fewer distant recurrences for recurrence score 16-20 and 7% fewer for recurrence score 21-25).
The researchers also found that women with a recurrence score of 10 or less had very low recurrence rates with hormone therapy alone, irrespective of age or other clinical factors. In addition, those with a recurrence score of 26 or higher had a distant recurrence rate of 13% despite chemotherapy and hormone therapy, indicating the need to develop more effective therapies for this group.
In summary, these data suggest that chemotherapy can be spared to all women older than 50 years with hormone receptor-positive, HER2-negative, node-negative breast cancer and a recurrence score of 0-25 (about 85% of women with breast cancer in this age group) and in all women 50 years or younger with hormone receptor-positive, HER2-negative, node-negative breast cancer and a recurrence score of 0-15 (about 40% of women with breast cancer in this age group). This means that thousands of women will be able to avoid chemotherapy, with all of its side effects, while still achieving excellent long-term outcomes.
Sparano J, et al. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score. Presented at ASCO 2018; Abstract LBA1.