Radiation instead of hormone therapy after lumpectomy for older people with early ER+ breast cancer

EMERALD: Endocrine Therapy oMission With Radiation in ER+ Breast Cancer: Assessing Quality of Life and Disease Control: a Prospective Phase II Trial

This trial tests whether giving radiotherapy alone after lumpectomy—while skipping endocrine (hormone) therapy—works for people aged 60 and older with early, low-risk ER+ breast cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 300 (estimated)
• Ages: 60 Years and up
• Sex: Female
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: radiation
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT06897488 on ClinicalTrials.gov

What this trial studies

This is a prospective Phase II trial that gives adjuvant radiotherapy as the sole systemic-sparing therapy after breast-conserving surgery in patients aged 60 or older with early-stage, low-risk ER+/PR+, HER2- breast cancer. Eligible tumors are T1-T2 with total size ≤3 cm, clinically node-negative, and have low proliferation (Ki-67 <20% or Oncotype score 0-10). The primary endpoint is 3-year distant metastasis-free survival, with secondary endpoints including health-related quality of life, ipsilateral breast tumor recurrence, local-regional recurrence, contralateral breast cancer, breast cancer-specific and overall survival, salvage treatments, toxicity, and long-term follow-up up to 11 years. Patients receive adjuvant radiotherapy and are followed regularly with clinical assessments and chart or phone-based follow-up for oncologic outcomes and quality-of-life measures.

Who should consider this trial

Good fit: Ideal candidates are people aged 60 or older with ER+/PR+, HER2-negative, early-stage breast cancer after lumpectomy (T1-T2 ≤3 cm), clinically node-negative, with low proliferation (Ki-67 <20% or Oncotype 0-10) who have discussed adjuvant options with a medical oncologist and who never start or discontinue endocrine therapy.

Not a fit: Patients with higher-risk features such as node-positive disease, HER2 amplification, larger tumors, high Ki-67, or those who need systemic endocrine or chemotherapy are unlikely to benefit from radiotherapy-alone and are not appropriate for this approach.

Why it matters

Potential benefit: If successful, this approach could allow selected older patients to avoid the side effects and burdens of endocrine therapy while maintaining good cancer control.

How similar studies have performed: Previous randomized trials have tested omitting radiation while giving endocrine therapy (e.g., CALGB 9343, PRIME II) and genomic "ultra-low" signatures have suggested some patients might safely omit endocrine therapy, but using radiotherapy as the only adjuvant treatment while omitting endocrine therapy is less well studied and is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Diagnosis of pathologically-confirmed invasive breast cancer
2. Age ≥ 60 years
3. Treatment with breast conserving surgery
4. Pathologic T stage of T1 or T2 with total tumor size ≤ 3cm including any component of DCIS that may exist in conjunction with invasive disease
5. Ki-67 . 20% and/or Oncotype 0-10 (Ultra Low)
6. Final surgical margins negative, defined as no tumor on ink. Lobular carcinoma in situ involving the final surgical margin will be disregarded.
7. Tumor must be estrogen receptor positive, progesterone receptor positive and HER2Neu non-amplified as per current College of American Pathologists guidelines
8. Clinical nodal stage cN0
9. If pathologic nodal staging is obtained, then pN0 or pN0(i+)
10. Patients have had or have a scheduled discussion with a breast medical oncologist regarding adjuvant treatment options
11. Patients who have met criteria 4.1.1-4.1.9 who never initiate endocrine therapy OR who initiate adjuvant endocrine therapy but discontinue it within 6 months of initiation \* In some clinical scenarios, patients may have a particularly small volume of tumor, making it not be feasible for all of these biomarkers to be evaluated. In this scenario, if the PI and/or Protocol Collaborators are able to document that a patient is being treated as if they have luminal A (biologically favorable) breast cancer then the patient is eligible for enrollment if all other eligibility criteria are met.

Exclusion Criteria:

1. Node positive disease (N1-3)
2. Metastatic disease (M1)
3. Grade 3 disease and lymphovascular space invasion in the tumor
4. Synchronous bilateral breast cancer
5. Receipt of neoadjuvant therapy
6. Diagnosis of a collagen vascular disease associated with an increased incidence of radiation toxicities such as scleroderma or systemic lupus erythematosis
7. Diagnosis of other cancer within the prior 5 years, excluding basal or squamous cell carcinoma of the skin that has been treated
8. Patient with psychiatric illness/social situations that would limit compliance with study requirements
9. Prior radiotherapy to the index breast or recurrent cancer of the breast
10. Known carrier of a mutation associated with predisposition to breast cancer development, including BRCA1 or BRCA2

Where this trial is running

Houston, Texas

• The University of Texas M. D. Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Simona Shatelman, MD — M.D. Anderson Cancer Center
• Study coordinator: Simona Shaitelman, MD

Conditions Breast Cancer