TAILORx: Why it Matters?

TAILORx (Trial Assigning Individualized Options for Treatment):
- Was the landmark prospective trial that validated use of the 21-gene recurrence score (Oncotype DX):
  - To guide adjuvant chemotherapy decisions in women with:
    - HR-positive, HER2-negative, axillary node-negative early breast cancer
- Its main practice-changing contribution was showing that:
  - Most women with an intermediate recurrence score:
    - Do not benefit from adjuvant chemotherapy:
      - Particularly those older than 50 years
Study design:
- The trial enrolled:
  - 9,719 women with HR-positive, HER2-negative, node-negative breast cancer
- Patients with a recurrence score (RS) 0 to 10 received endocrine therapy alone; those with RS 26 to 100 received chemoendocrine therapy; and those with RS 11 to 25 were randomized to endocrine therapy alone versus chemoendocrine therapy
Primary result:
- Among women with RS 11 to 25:
  - Endocrine therapy alone was noninferior to chemoendocrine therapy for invasive disease–free survival:
  - At 9 years:
    - Invasive disease–free survival was 83.3% with endocrine therapy alone versus 84.3% with chemoendocrine therapy
  - Distant recurrence rates were also very similar:
    - This established that for the overall randomized group:
      - Adding chemotherapy did not provide a clinically meaningful benefit
- Age-specific nuance:
  - The critical nuance from TAILORx is age
  - In women 50 years or younger:
    - There appeared to be some chemotherapy benefit in subsets with RS 16 to 25:
      - Especially at the upper end of that range
  - By contrast, women older than 50 with RS 11 to 25 generally did not benefit from chemotherapy
  - The NCI summary estimated that chemotherapy can be safely avoided in about 70% of women with this common breast cancer subtype, including:
    - Any age with RS 0 to 10
    - Age > 50 with RS 11 to 25
    - Age ≤ 50 with RS 11 to 15
Low-score group (RS 0 to 10):
- The earlier prospective TAILORx report showed that women with RS 0 to 10 treated with endocrine therapy alone had very low recurrence rates:
  - Supporting omission of chemotherapy in this low-risk group
- High-score group (RS 26 to 100):
  - Patients with RS 26 to 100 were assigned to chemotherapy plus endocrine therapy
  - Follow-up analyses supported the standard recommendation to offer chemotherapy to this high-risk group:
    - NCI reported that women in this category had strong 5-year outcomes with chemoendocrine therapy:
      - Reinforcing that these patients should still be considered for systemic intensification rather than endocrine therapy alone
Clinical risk analysis:
- A secondary analysis integrating clinical risk (tumor size and grade) found that clinical risk adds prognostic information:
  - But was not clearly predictive of chemotherapy benefit in the overall population:
    - However, in women 50 years or younger, chemotherapy benefit was more apparent in those with RS 16 to 20 and high clinical risk, and in those with RS 21 to 25 regardless of clinical risk
Practical takeaways for the surgical oncologist:
TAILORx matters because it reframes postoperative discussions after definitive surgery in node-negative HR+ / HER2- disease:
- Genomic testing is central to adjuvant planning after surgery in appropriate patients
- TAILORx made the recurrence score part of standard decision-making:
  - Not just a prognostic adjunct
- Chemotherapy can often be omitted in postmenopausal or older patients with RS 11 to 25:
  - Which is highly relevant when counseling patients after lumpectomy or mastectomy
- In premenopausal or younger patients, especially ≤v50 years with RS 16 to 25:
  - The conversation is more nuanced:
    - These patients may derive benefit from chemotherapy:
      - Though some experts note that part of this benefit may reflect ovarian function suppression rather than direct cytotoxic effect alone
TAILORx applies to node-negative disease
- For 1 to 3 positive nodes:
  - The more relevant prospective trial is RxPONDER, not TAILORx
Bottom line:
- TAILORx changed practice by showing that adjuvant chemotherapy is unnecessary for most women with node-negative HR-positive / HER2-negative early breast cancer who have a midrange Oncotype DX recurrence score, particularly those older than 50
- The major exception is the younger / premenopausal subgroup with RS 16 to 25:
  - Where chemotherapy may still offer benefit and multidisciplinary discussion remains essential
Key references:
- Sparano JA, Gray RJ, Makower DF, et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med. 2018;379:111-121.
- Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer. N Engl J Med. 2019;380:2395-2405.
- National Cancer Institute. TAILORx trial finds most women with early breast cancer do not benefit from chemotherapy. 2018.
  National Cancer Institute PDQ. Breast Cancer Treatment (PDQ®), updated 2025.