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Reference: TAILORx trial (N Engl J Med 2018 Jun 3 early online) (level 2 [mid-level] evidence)
- For women having endocrine therapy following surgery for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, axillary node-negative breast cancer, the benefits of adjuvant chemotherapy is uncertain if there is a moderate risk of recurrence (defined here as an Oncotype DX 21-gene recurrence score of 11 to 25).
- In the TAILORx trial, almost 7,000 of these women were randomized to endocrine therapy alone vs. adjuvant chemotherapy plus endocrine therapy.
- There was no significant difference between groups in the risk of death, invasive disease recurrence, or second primary cancer at median 90 months in the intention-to-treat (hazard ratio 1.08, 95% CI 0.94-1.24) or as-treated (hazard ratio 1.14, 95% CI 0.99-1.31) analyses. However, the 95% CI’s, particularly for the as-treated analysis, cannot exclude a clinically important increased risk of harm with endocrine therapy alone.
Breast cancer is most commonly hormone receptor (HR)-positive / human epidermal growth factor receptor 2 (HER2)-negative (J Natl Cancer Inst 2014). Endocrine therapy following surgery is recommended for axillary node-negative breast cancers of this type (Lancet 2017). Adjuvant chemotherapy should be considered if there is a high risk of recurrence (Lancet 2017) and has been considered for many women with early-stage cancer. However, its value is unclear if the risk of recurrence is moderate. In the TAILORx trial, 6,907 moderate-risk women who had primary surgical therapy for HR-positive, HER2-negative, axillary node-negative breast cancer were randomized to endocrine therapy alone vs. chemoendocrine therapy (adjuvant chemotherapy plus endocrine therapy). A moderate risk of recurrence was defined as an Oncotype DX 21-gene recurrence score of 11 to 25 (score range 0-100, with higher scores indicating greater risk). The primary outcome was invasive disease-free (IDF) survival, defined as freedom from death, invasive disease recurrence, and second primary cancer.
Fewer patients in the endocrine therapy alone group did not adhere to allocated therapy (5.4% had chemotherapy, while 18.4% in the chemoendocrine therapy group did not have chemotherapy) or were excluded from analyses after randomization (in 1.7% vs. 4%). The two treatment groups had similar rates of IDF survival at median 90 months: 83.3% with endocrine therapy alone vs. 84.3% with chemoendocrine therapy (hazard ratio [HR] for not achieving IDF survival 1.08, 95% CI 0.94-1.24). They also had similar rates of overall survival at median 96 months (93.9% vs. 93.8%, HR for death 0.99, 95% CI 0.79-1.22) and freedom from recurrence (92.2% vs. 92.9%, HR for recurrence 1.11, 95% CI 0.9-1.37). In as-treated analyses, no significant differences in rates of IDF survival or its components were found, but there was a non-significant increased risk of not achieving IDF survival with endocrine therapy alone (HR 1.14, 95% CI 0.99-1.31).
The TAILORx trial found that chemotherapy in addition to endocrine therapy may not be beneficial in women who had primary surgical therapy for HR-positive, HER2-negative, axillary node-negative breast cancer with a moderate risk of recurrence as defined by an Oncotype DX score of 11 to 25. Although adjuvant chemotherapy did not significantly change the rates of important outcomes in the intention-to-treat or as-treated analyses, the 95% CI’s could not exclude clinically important differences. This concern is exacerbated by the greater proportion of patients allocated to chemoendocrine therapy who did not adhere to the treatment or were excluded from analyses. On the other hand, chemotherapy is accompanied by serious adverse events and reduced quality of life, and patients may choose to avoid it unless there is a clearly demonstrated benefit. The TAILORx trial did not find a benefit with adjuvant chemotherapy for women with the type of breast cancer included in this trial, indicating that endocrine therapy alone may be considered as an option in this patient population.
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