Comparing radiation therapy and hormone therapy for older women with early stage breast cancer

ExclUsive endocRine Therapy Or Radiation theraPy for Women Aged ≥70 Years With Luminal A-like Early Stage Breast Cancer (EUROPA): a Randomized Phase 3 Trial

This study is testing whether radiation therapy or hormone therapy is better for older women with early stage breast cancer in terms of health and quality of life after surgery.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 926 (estimated)
• Ages: 70 Years and up
• Sex: Female
• Sponsor: Azienda Ospedaliero-Universitaria Careggi (Academic / other)
• Drugs / interventions: denosumab, chemotherapy, radiation
• Locations: 1 site (Florence)
• Trial ID: NCT04134598 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of exclusive radiation therapy versus exclusive endocrine therapy in women aged 70 and older who have early stage breast cancer. The study aims to determine if radiation therapy can provide better health-related quality of life outcomes compared to hormone therapy after breast-conserving surgery. Participants will receive either breast irradiation or hormone therapy with medications like letrozole or tamoxifen, with the goal of achieving similar disease control while minimizing long-term side effects. The trial is designed to assess the impact of these treatments on patient well-being and overall health.

Who should consider this trial

Good fit: Ideal candidates for this study are women aged 70 years and older with early stage, hormone receptor-positive breast cancer who have undergone breast-conserving surgery.

Not a fit: Patients with advanced breast cancer or those who have not undergone surgery may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved quality of life for elderly women with early stage breast cancer by identifying a more effective treatment option.

How similar studies have performed: Previous studies have shown promising results with hypofractionated radiation therapy, suggesting that this approach may be effective, but this specific comparison is novel.

Eligibility criteria

Inclusion Criteria:

* Women aged ≥70 years;
* histologically proven invasive adenocarcinoma of the breast;
* pathological T1 (pT1) stage (clinical T1-2 \[cT1-2\] stage is allowed);
* clinical and pathological N0 (cN0 and pN0) stage (isolated tumor cells \[i+\] allowed);
* any tumor grade (if pT ≤10 mm), G1-2 tumor grade (if pT between 11 and 19 mm);
* Luminal-A by immunohistochemistry (IHC)-based on local assessment (consistent with 14th St. Gallen consensus definition):

  * ER/PgR+ (defined as ≥10% by IHC staining),
  * Human epidermal growth factor receptor 2 (HER2)- (0 or 1+ following IHC staining and proven negative by in-situ hybridization \[ISH\] in case of 2+), and
  * Ki67 ≤20% by IHC staining;
* surgically treated with BCS with or without sentinel node biopsy (SNB);
* no clinical evidence of distant metastases. Imaging work up is not mandatory to enter the trial. If there are signs/symptoms suggesting the presence of local relapse or distant metastasis, an appropriate work up should be performed according to the treating physician standard practice. A patient with confirmed local relapse or distant metastasis will no longer be eligible for the trial;
* postoperative final surgical margins negative (no ink on tumor);
* baseline HRQoL questionnaires completion;
* adjuvant bisphosphonates and denosumab are allowed;
* before patient registration/randomization, written informed consent must be given.

Exclusion Criteria:

* Preoperative systemic treatments (i. e., chemotherapy, endocrine therapy);
* current treatment with any hormonal agents such as tamoxifen, raloxifene or other selective estrogen receptor modulators (SERMs), either for osteoporosis or BC prevention (patients are eligible if these medications are discontinued prior to randomization);
* prior breast or thoracic RT;
* known disorders associated with a higher risk for complications following RT such as collagen vascular disease, dermatomyositis, systemic lupus erythematosis or scleroderma;
* prior diagnosis, detection, or treatment of any other invasive cancer (except basal or squamous cell carcinoma of the skin that has been definitely treated);
* any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; these conditions should be discussed with the patient before registration;
* patients must not be considered a poor medical risk due to serious, uncontrolled medical disorder, non-malignant systemic disease, or active uncontrolled infection. Examples include but are not limited to uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction or uncontrolled major seizure disorder.

Where this trial is running

Florence

• Azienda Ospedaliero-Universitaria Careggi, Florence University — Florence, Italy (Recruiting)

Study contacts

• Principal investigator: Icro Meattini, MD,Prof — University of Florence, Florence, Italy
• Study coordinator: Icro Meattini, MD,Prof

Conditions Breast Cancer; Partial Breast Irradiation; Radiation Therapy; Endocrine Therapy; Breast Conserving Surgery; Elderly; Health Related Quality of Life; Patients Reported Outcome Measures