Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer
- Study type
- Clinical trial
- Study name
- TAILORx
- Phase
- Phase 3
- Design
- Prospective trial with randomisation of the intermediate-score group; non-inferiority design
- Sample size
- 10273 women (6711 patients randomised with a recurrence score of 11 to 25)
- Source
- N Engl J Med · 2018
- Trial registration
- NCT00310180
In plain words
The 21-gene test (Oncotype DX) is done on tumour tissue and gives a "recurrence score". This large study showed that most women with hormone-positive, HER2-negative breast cancer that has not spread to the lymph nodes and who have a middle score (11 to 25) do not benefit from chemotherapy, and hormone therapy alone is enough; the exception is some women aged 50 or younger with a score of 16 to 25.
Key results
Treatment arms and regimens
Standard oral adjuvant endocrine therapy at the physician's choice: tamoxifen alone, an aromatase inhibitor (anastrozole, letrozole or exemestane) alone, or tamoxifen followed by an aromatase inhibitor, for 5 or 10 years. Median duration of endocrine therapy 5.4 years (about 35% more than 5 years); 91% of postmenopausal women received an aromatase inhibitor and 78% of premenopausal women received tamoxifen alone or tamoxifen followed by an aromatase inhibitor, and ovarian suppression was used in 13% of premenopausal women. No specific dose is set in the sources reviewed.
Standard adjuvant combination chemotherapy at the physician's choice followed, within 4 weeks of the last chemotherapy dose, by the same endocrine therapy as the other arm. The most common regimens in patients receiving chemotherapy: docetaxel and cyclophosphamide (56%) and anthracycline-containing regimens (36%). No specific dose is set in the sources reviewed.
Source of the regimen details: Full text of the paper (PMC6172658) and ClinicalTrials.gov NCT00310180; chemotherapy and endocrine regimens were at the treating physician's choice and no specific doses are set in these sources
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women aged 18 to 75 years with operable breast cancer, oestrogen and/or progesterone receptor-positive (per local laboratory), HER2-negative (FISH, or IHC 0 or 1+), without axillary lymph node involvement (sentinel node biopsy and/or axillary dissection), tumour size 1.1 to 5.0 cm (or 0.5 to 1.0 cm with intermediate or high nuclear or histological grade or lymphovascular invasion), for whom adjuvant chemotherapy was recommended or could be considered under the NCCN guideline; no prior chemotherapy or radiotherapy for this cancer, with clear surgical margins and enrolment within 84 days of surgery. Of 10,273 women registered, 9719 eligible patients with follow-up data were analysed: recurrence score 11 to 25 in 69% (randomised), 10 or less in 17% (endocrine therapy only) and 26 or more in 14% (chemotherapy and endocrine therapy).
Endpoints
Primary outcome: invasive disease-free survival (freedom from invasive disease recurrence, second primary cancer or death), aiming to show non-inferiority of endocrine therapy alone.
Safety and side effects
The main report gave no data on treatment adverse events, and data on chemotherapy-induced menopause were not collected. The safety outcome of the strategy was the omission of chemotherapy: in the score 11 to 25 group, endocrine therapy alone was non-inferior for invasive disease-free survival (HR 1.08; 95% CI 0.94 to 1.24), and 9-year overall survival was similar (93.9% versus 93.8%). Non-adherence to the assigned treatment was 5.4% in the endocrine therapy group and 18.4% in the chemotherapy group.
Clinical significance and place in guidelines
TAILORx became one of the most important de-escalation studies and established the use of gene expression assays to guide decisions about adjuvant chemotherapy. ESMO guideline (Pan-Asian adapted version 2024): when the indication for adjuvant chemotherapy is uncertain, gene expression assays can be used to guide the decision [I, B].
Limitations
Node-negative patients only; the benefit seen in younger women may be partly due to ovarian suppression by chemotherapy; non-adherence to the assigned treatment in some patients.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.