ESR1Real World Assessment Prevalence Study (ESRA)

Many patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer in the first therapy line is endocrine sensitive. For these patients the established 1st line standard therapy is a combination of a CDK4/6 inhibitor and an aromatase inhibitor. This combination therapy is usually given until clinical progression.

Recent studies suggest that a detection of a somatic ESR1 mutation in the ctDNA can be clinically used to prompt an earlier change from the aromatase inhibitor to a selective estrogen receptor degrader.

For implementation in the clinical routine it is important to gain knowledge about the dynamics of ESR1 mutation in HR+/HER2- advanced breast cancer patients during their first line therapy. At the beginning of the first line therapy about 5-8% of patients show an ESR1 mutation. An identification of patients with resistance to aromatase inhibitors at that timepoint might not be feasible and cost-efficient. At the timepoint of clinical progression up to 30-40% of patients will have acquired an ESR1 mutation. Knowledge about the mutation frequencies at different timepoints will be very helpful to direct testing strategies for implementing testing broadly in a population.

The aim of this study is to test ESR1 mutation frequencies in groups of patients (single time test per patient) with no clinical progression and different durations under first-line treatment with aromatase inhibitor and CDK4/4 inhibitor.

Study Overview

• Status: Not yet recruiting
• Conditions: HR+/HER2- aBC Undergoing 1L Treatment With CDK4/6i (Palbociclib, Abemaciclib or Ribociclib) and AI (Anastrozole or Letrozole)
• Intervention / Treatment: Diagnostic test: ESR1 testing

• Study Type: Interventional
• Enrollment (Estimated): 1550
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sponsor's study office; Phone Number: +49 9131 91880613; Email: esra@ifg-erlangen.de

Study Locations

• Germany
  • Ansbach, Germany, 91522
    • ANregiomed gKU, AöR, Klinikum Ansbach
    • Contact: Thomas Hildebrandt, PD Dr.; Phone Number: +49 981 484 2256; Email: thomas.hildebrandt@anregiomed.de
  • Bremen, Germany
    • Hämato-Onkologische Praxis im Medicum; Brustzentrum
    • Contact: Ralf Meyer, Dr.; Phone Number: +49 421 6960960; Email: ralfmeyer@home-bremen.com
  • Celle, Germany, 29223
    • Allgemeines Krankenhaus Celle; Brustzentrum
    • Contact: Michael Berghorn, Dr.; Phone Number: +49 5141 721151; Email: michael.berghorn@akh-celle.de
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus Dresden, Frauenklinik
    • Contact: Theresa Link, Dr.; Phone Number: +49 351 4586863
  • Düsseldorf, Germany, 40235
    • Kostara Gyn. Onkoloy Clinic Research UG
    • Contact: Athina Kostara, Dr.; Phone Number: +49 211 53809241; Email: athina.kostara@gynoncology-cr.de
  • Erlangen, Germany, 91054
    • Universitätsklinikum Erlangen, Frauenklinik
    • Contact: Peter Andreas Fasching, Prof. Dr.; Phone Number: +4991318533572; Email: peter.fasching.studien@uk-erlangen.de
  • Homburg, Germany, 66421
    • Universitätsklinikum; Frauenheilkunde, Geburtshilfe & Reproduktionsmedizin
    • Contact: Julia Radosa, Prof. Dr.; Phone Number: +49 6841 16280; Email: julia.radosa@uks.eu
  • Ilsede, Germany, 31241
    • Frauenarztpraxis Baerens
    • Contact: Dirk-Toralf Baerens; Phone Number: +49 5172 2221; Email: baerens@online.de
  • Loerrach, Germany, 79539
    • OncoStudies Lörrach, Onkologie Dreiländereck
    • Contact: Gwen-Jana Töppler, Dr.; Phone Number: +49 7621 5791570; Email: toeppler@onkologie-loerrach.de
  • München, Germany, 80637
    • Rotkreuzklinikum München; Brustzentrum
    • Contact: Michael Braun, Prof.; Phone Number: +49 89 130330; Email: Michael.Braun@swmbrk.de
  • München, Germany, 81241
    • Hämatologie OnkologieMünchen Pasing MVZ GmbH
    • Contact: Matthias Zingerle, Dr.; Phone Number: +49 898299660; Email: zingerle@onkolohie-pasing.de
  • Münster, Germany, 48145
    • MVZ Media Vita am St. Franziskus Hospital; Frauenklinik
    • Contact: Christian Eichler, PD Dr.; Phone Number: +49 251 9355580; Email: christian.eichler@sfh-muenster.de
  • Münster, Germany, 48727
    • Universitätsklinikum Münster; Frauenklinik
    • Contact: Opitz Carl, Dr.; Phone Number: +49 251 8344111; Email: carl.opitz@ukmuenster.de
  • Potsdam, Germany, 14467
    • Klinikum Ernst von Bergmann; Frauenheilkunde
    • Contact: Dorothea Fischer, Prof. Dr.; Phone Number: +49 331 241 35602; Email: Dorothea.Fischer@klinikumevb.de
  • Rosenheim, Germany, 83022
    • medicum Rosenheim MVZ GmbH; Innere Onkologie
    • Contact: Rudolf Pihusch, Prof. Dr.; Phone Number: +49 803134511; Email: Rudolf.Pihusch@pihusch.de
  • Torgau, Germany, 04860
    • Kreiskrankenhaus Torgau; Brustzentrum
    • Contact: Eike Simon, Dr.; Phone Number: +49 3421 77-2520; Email: simon@kkh-torgau.de
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen; Department für Frauengesundheit
    • Contact: Andreas Hartkopf, Prof. Dr.; Phone Number: +49 7071 2982211; Email: andreas.hartkopf@med.uni-tuebingen.de
  • Westerstede, Germany, 26655
    • Medizinische Studiengesellschaft Nord-West GmbH; Onkologie
    • Contact: Jan Janssen, Dr.; Phone Number: +49 4488521880; Email: gensch-janssen@t-online.de
  • Wiesbaden, Germany, 65199
    • Helios Dr. Horst Schmidt Kliniken; Gynäkologie
    • Contact: Michael Eichbaum, Prof. Dr.; Phone Number: +49 611 432377; Email: michael.eichbaum@helios-gesundheit.de
  • Wolfenbüttel, Germany, 38304
    • Frauenärzte am Schloß; Praxis für Gynäkologie und Geburtshilfe
    • Contact: Julia von Ehr, Dr.; Phone Number: +49 5331 2510; Email: ju.vonehr@gmail.com
  • Würzburg, Germany, 97080
    • Universitätsklinik Würzburg; Frauenklinik und Poliklinik
    • Contact: Jessica Salmen, Dr.; Phone Number: +49 931 20125194; Email: salmen_J@ukw.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject must be female or male and aged ≥ 18 years on the day of signing informed consent
2. Patient has locally advanced or metastatic breast cancer not amenable to curative treatment
3. Patient has HER2- breast cancer confirmed by local laboratory, defined as a negative in situ hybridization test or an IHC status of 0 or 1+. If IHC is 2+, a negative in situ hybridization (FISH, CISH, or SISH) test is required to confirm the HER2-negative status (based on the most recently analyzed tissue sample tested by a local laboratory)
4. Histologically confirmed ER-positive and/ or PgR-positive breast cancer determined by core biopsy according to local in-house standard
5. Patient has already initiated or is about to initiate first-line therapy with a CDK4/6 inhibitor (any CDK4/6i) in combination with an aromatase inhibitor (non-steroidal AI). Treatment must be intended as first-line systemic therapy for advanced or metastatic disease
6. Information about prior oncological therapies against the HR+/HER2- BC must be available
7. Data about histo-pathological report must be available, including hormone receptor status, tumor histology, tumor grading and HER2 immunohistochemistry
8. Inclusion in the study occurs as a single, one-time event for each patient, within one of the 9 defined cohorts

Exclusion Criteria:

1. Patients with an interruption of ongoing first-line CDK4/6i plus AI therapy exceeding 1 month for either CDK4/6i or AI
2. Patients receiving any other systemic anticancer therapy for HR+/HER2- aBC, except for LHRH agonists, bisphosphonates, or denosumab
3. Clinical evidence of progression at the timepoint of study inclusion
4. Patients have already completed ≥ 1L of systemic therapy for aBC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort (0m); Before start of the 1L treatment (anticipated AI + CDK4/6i)	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (6-8m): Patients in months 6, 7 or 8 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (9-11m); Patients in months 9, 10 or 11 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (12-14m); Patients in months 12, 13 or 14 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (15-17m); Patients in months 15, 16 or 17 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (18-20m); Patients in months 18, 19 or 20 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (21-23m); Patients in months 21, 22 or 23 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (24-26m); Patients in months 24, 25 or 26 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.
Experimental: Cohort (27-29m); Patients in months 27, 28 or 29 of the 1L treatment	Diagnostic test: ESR1 testing; Study procedures comprise of a blood sample for ESR1 mutation testing and blood samples for translational research. ESR1 test results from a central testing facility are communicated back to the study site. Treatment of patients will continue as per discretion of the treating physician and will be documented during a single timepoint 3 months post inclusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PO1	mutation frequency of ESR1 mutations as assessed in blood sample	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SO1	ESR1 mutation frequencies according to age and BMI	Day 1
SO2	ESR1 mutation frequencies according to type of CDK4/6i therapy	Day 1
SO3	ESR1 mutation frequencies according to type of aromatase inhibitor	Day 1
SO3	ESR1 mutation frequencies according to menopausal status	Day 1
SO4	ESR1 mutation frequencies according to HER2 status (HER2 0, HER2 ultralow, HER2 low)	Day 1
SO5	ESR1 mutation frequencies according to extent of estrogen and progesterone receptor expression	Day 1
SO6	ESR1 mutation frequencies according to tumor grading	Day 1
SO7	ESR1 mutation frequencies according to previous therapies (de novo patients vs. previous adjuvant therapy)	Day 1

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
EO1	To explore the molecular landscape accompanying ESR1 mutations, including co-occurring genomic alterations (e.g., PIK3CA, TP53, etc.) detected in ctDNA	Day 1
EO2	To investigate associations between ESR1 mutation characteristics (variant type, allele frequency) and clinical or molecular features, including prior AI exposure.	Day 1
EO3	To perform transcriptomic profiling (bulk RNA-seq) of circulating immune cells (PBMCs) to identify immune activation or suppression signatures associated with clinical progression (PD vs. non-PD).	Day 1
EO4	To explore potential biomarkers of endocrine resistance and immune modulation, integrating ctDNA muta	Day 1

Collaborators and Investigators

• Sponsor: Institut fuer Frauengesundheit
• Collaborators: Universitätsklinikum Erlangen; AGO Breast (Arbeitsgemeinschaft Gynäkologische Onkologie); data4treat GmbH; BioMedStatistics GmbH; ClinSol GmbH & Co KG
• Investigators: Study Director: Peter Andreas Fasching, Prof. Dr., AGO-B e.V. c/o Frauenklinik des Universitätsklinikums Erlangen; Study Chair: Volkmar Müller, Prof. Dr., Universitätsklinikum Hamburg-Eppendorf; Klinik und Poliklinik für Gynäkologie; Study Chair: Tanja Fehm, Prof. Dr., Frauenklinik des Universitätsklinikums Düsseldorf

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: September 8, 2026
• First Submitted That Met QC Criteria: September 8, 2026
• First Posted (Actual): September 14, 2026

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 8, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: IFG-01-2026

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No