ExclUsive endocRine Therapy Or Radiation theraPy for Women Aged ≥70 Years Early Stage Breast Cancer

NCT04134598 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: EUROPA
• Study Type: interventional
• Target: 926
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale and relevance for patients and the scientific community. In low risk early stage patients ≥70 years, exclusive radiation therapy (RT) approach might be superior in terms of Health-Related Quality of Life (HRQoL), when compared to exclusive endocrine therapy (ET) following breast-conserving surgery (BCS). Assuming an equal rate of disease control, unnecessary long-term toxicity of ET may be avoided.

Conditions

Breast Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Patient reported outcome measures (PROM) HRQoL as assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30

  EORTC Quality of Life Questionnaire (QLQ) C30.The QLQ-C30 is a cancer HRQoL questionnaire using PROMs for individual patient management. It includes five function domains (physical, emotional, social, role, cognitive), eight symptoms (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnea, and appetite loss), as well as global health/quality-of-life and financial impact. Subjects respond on a four-point scale from "not at all" to "very much" for most items. Raw scores are linearly converted to a 0-100 scale with higher scores reflecting higher levels of function and higher levels of symptom burden.

  Change from baseline at 24 months

• Time to ipsilateral breast tumor recurrence (IBTR)

  Time to ipsilateral breast tumor recurrence (IBTR)

  60 months

Secondary Outcomes (9)

• Patient reported outcome measures (PROM) HRQoL as assessed by EORTC Quality of Life Questionnaire (QLQ) BR45 Breast module

  Change from baseline at 24 months

• Patient reported outcome measures (PROM) HRQoL as assessed by EORTC Quality of Life Questionnaire (QLQ) ELD14 Elderly module

  Change from baseline at 24 months

• Time to locoregional recurrence (LRR)

  24 months

• Time to contralateral breast cancer (CBC)

  24 months

• Time to distant metastases (DM)

  24 months

Study Arms (2)

Breast Irradiation (RT)

EXPERIMENTAL

Breast Irradiation (RT)

Radiation: Breast irradiation (RT)

Endocrine Therapy (ET)

ACTIVE COMPARATOR

Endocrine Therapy (ET)

Drug: Endocrine Therapy (ET): letrozole, anastrozole, exemestane, tamoxifen

Interventions

Breast irradiation (RT) RADIATION

Irradiation of volume's portion Index quadrant) or whole volume of the residual breast.

Also known as: Partial Breast Irradiation (PBI), Whole Breast Irradiation (WBI)

Breast Irradiation (RT)

Endocrine Therapy (ET): letrozole, anastrozole, exemestane, tamoxifen DRUG

Adjuvant endocrine therapy as per local policy (letrozole/anastrozole/exemestane/tamoxifene for 5-year or switch schedules aromatase inhibitors/tamoxifen for 5-year).

Also known as: Hormonal therapy

Endocrine Therapy (ET)

Eligibility Criteria

• Age: 70 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead
• University of Florence: collaborator

Study Sites (1)

Azienda Ospedaliero-Universitaria Careggi, Florence University

Florence, 50141, Italy

Location

Related Publications (3)

• Meattini I, Poortmans PMP, Marrazzo L, Desideri I, Brain E, Hamaker M, Lambertini M, Miccinesi G, Russell N, Saieva C, Strnad V, Visani L, Kaidar-Person O, Livi L. Exclusive endocrine therapy or partial breast irradiation for women aged >/=70 years with luminal A-like early stage breast cancer (NCT04134598 - EUROPA): Proof of concept of a randomized controlled trial comparing health related quality of life by patient reported outcome measures. J Geriatr Oncol. 2021 Mar;12(2):182-189. doi: 10.1016/j.jgo.2020.07.013. Epub 2020 Jul 29.

  PMID: 32739355 BACKGROUND

• Meattini I, De Santis MC, Visani L, Scorsetti M, Fozza A, Meduri B, De Rose F, Bonzano E, Prisco A, Masiello V, La Rocca E, Spoto R, Becherini C, Blandino G, Moscetti L, Colciago RR, Audisio RA, Brain E, Caini S, Hamaker M, Kaidar-Person O, Lambertini M, Marrazzo L, Saieva C, Spanic T, Strnad V, Wheelwright S, Poortmans PMP, Livi L; EUROPA Trial Investigators. Single-modality endocrine therapy versus radiotherapy after breast-conserving surgery in women aged 70 years and older with luminal A-like early breast cancer (EUROPA): a preplanned interim analysis of a phase 3, non-inferiority, randomised trial. Lancet Oncol. 2025 Jan;26(1):37-50. doi: 10.1016/S1470-2045(24)00661-2. Epub 2024 Dec 12.

  PMID: 39675376 BACKGROUND

• Ho AY, Bellon JR. Overcoming Resistance - Omission of Radiotherapy for Low-Risk Breast Cancer. N Engl J Med. 2023 Feb 16;388(7):652-653. doi: 10.1056/NEJMe2216133. No abstract available.

  PMID: 36791166 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Anastrozole; exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Study Officials

• Lorenzo Livi, MD,Prof

  University of Florence, Florence, Italy

  STUDY CHAIR

• Philip M Poortmans, MD,PhD,Prof

  Iridium Kankernetwerk - University of Antwerp; Wilrijk-Antwerp, Belgium

  STUDY CHAIR

• Icro Meattini, MD,Prof

  University of Florence, Florence, Italy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Professor

Study Record Dates

• First Submitted: October 17, 2019
• First Posted: October 22, 2019
• Study Start: February 8, 2021
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: August 29, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)