For women with node-negative, hormonal receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative, early breast cancer, the 21-gene recurrence score (RS) assay can be used to predict risk of recurrence and to tailor treatment. Patients with low RS (0-10) have low risk of recurrence when treated with endocrine therapy alone, while patients with high RS (≥26) may derive benefit from addition of chemotherapy. However, for patients with a RS from 11 to 25, which includes nearly two-thirds of patients with early breast cancer, the relative benefit of adjuvant chemotherapy is unclear.
The phase III TAILORx trial (N = 10,273) was designed to evaluate the benefit of adding adjuvant chemotherapy to endocrine therapy in women with node-negative, HR-positive, HER2-negative early breast cancer based on prognosis determined by the 21-gene recurrence score assay. Patients with low scores (RS 0 to 10) received endocrine therapy only and patients with high scores (RS 25 to 100) received chemotherapy plus endocrine therapy, while the 6,711 patients with intermediate RS (11 to 25) were randomized to receive either endocrine therapy alone or adjuvant chemotherapy followed by endocrine therapy.
During the Plenary Session at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, Joseph Sparano, MD (Montefiore Medical Center, New York, United States), presented results from this trial, which were simultaneously published in The New England Journal of Medicine. In patients with intermediate RS, endocrine therapy alone was non-inferior to adjuvant chemotherapy plus endocrine therapy. Nine-year rates of invasive disease-free survival (iDFS) were 83.3% with endocrine therapy, compared to 84.3% for adjuvant chemotherapy and endocrine therapy (HR 1.08, P = .26). Noninferiority for endocrine therapy alone versus chemotherapy plus endocrine therapy was also observed in key secondary endpoints, including distant recurrence-free interval (94.5% vs 95.0%), recurrence-free interval (92.2% vs 92.9%), and overall survival (93.9% vs 93.8%). However, in an exploratory analysis, a benefit for chemotherapy was found in women under 50 years of age with a recurrence score of 15 to 25. Conversely, women 50 years of age or younger with RS 0-15 had good prognosis with endocrine therapy alone.
Patients with low scores who received endocrine therapy alone had a 3% rate of distant recurrence, while patients with high scores had a 13% rate of distant recurrence, despite the addition of chemotherapy to endocrine therapy.
In her discussion of this trial, Lisa Carey, MD (University of North Carolina Lineberger Comprehensive Cancer Center, North Carolina, United States), applauded this trial for its efforts to identify patients with early breast cancer for whom adjuvant chemotherapy is unnecessary. Based on these practice-changing results, up to 85% of women with node-negative HR-positive and HER2-negative early-stage breast cancer can be spared adjuvant chemotherapy, especially postmenopausal with RS of 25 or lower, as well as women 50 years of age with RS of 15 or lower for whom endocrine therapy alone is sufficient. Dr Carey also highlighted that TAILORx enrolled patients with clinically low-risk breast cancer and that hopefully ongoing clinical trials will address the usefulness of genomic assays in HR-positive patients with positive axillary nodes. In addition, she highlighted the unmet need for assays to help with decision making in early HER2-positive and triple-negative breast cancer.