Integrated Testing Strategy for Simultaneous Detection of ESR-1 and gBRCA Mutations Via Liquid Biopsy in HR+/HER2- Metastatic Breast Cancer (mBC) Patients, (L2-268)

Development and Validation of an Integrated Testing Strategy for Simultaneous Detection of ESR-1 and gBRCA Mutations Via Liquid Biopsy in HR+/HER2- Metastatic Breast Cancer (mBC) Patients, and the Creation of a Digital Gene Library to Support an Evidence-based Diagnostic Algorithm

Development and validation of an integrated testing strategy for simultaneous detection of ESR-1 and gBRCA mutations via liquid biopsy in HR+/HER2- metastatic breast cancer (mBC) patients, and the creation of a digital gene library to support an evidence-based diagnostic algorithm

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer, Metastatic

Detailed Description

Breast cancer is the most prevalent type of tumor and the primary cause of cancer-related deaths among women globally (1). Approximately two-thirds of these tumors express hormone receptors (HR) and lack HER2 overexpression and/or amplification (2). Throughout treatment, resistance frequently develops, with underlying mechanisms that remain largely undefined (3).

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Nicola Fusco, MD; Phone Number: 00390294372079; Email: nicola.fusco@ieo.it
• Study Contact Backup: Name: francesca lombardi, biologist; Phone Number: 00390257489425; Email: francesca.lombardi@ieo.it

Study Locations

• Italy
  • Italy
    • Milan, Italy, Italy, 20141
      • Recruiting
      • European Institute of Oncology
      • Contact: Nicola Fusco, MD; Phone Number: +300294372079; Email: nicola.fusco@ieo.it
      • Contact: Elena Guerini Rocco, MD; Phone Number: +390294372871; Email: elena.guerinirocco@ieo.it

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Eligible patients will be identified and enrolled in the study.

• Blood sample collection and plasma purification Blood samples will be collected, and plasma will be purified following biobank procedures.
• ESR1 and gBRCA liquid biopsy-based testing

Description

Inclusion Criteria:

• Participants must have a confirmed diagnosis of estrogen receptor-positive (ER+) and/or progesterone receptor-positive (PgR+) breast cancer through histological and/or cytological examination by the local laboratory Participants must exhibit HER2-negative breast cancer

  1. or 2+). If IHC is 2+, a negative in situ hybridization (Fluorescent in situ hybridization (FISH), Chromogenic in situ hybridization (CISH), or Silver-enhanced in situ hybridization (SISH)) test is required by local laboratory testing.

     • Participants should be in an advanced or metastatic setting including both those prior to the initiation of treatment for metastatic disease and those who experienced progression following treatment with cyclin-dependent kinases (CDK)4/6 inhibitors. However, the primary tumor should be treated according to the standard of care.
     • Written informed consent must be signed and dated by the patient and the investigator prior to inclusion.

Exclusion Criteria:

• Unable to provide written informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
HR+/HER2- metastatic breast cancer (mBC) patients; breast

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the creation of a digital gene library to support an evidence-based diagnostic algorithm	Optimize the patient journey for individuals with metastatic breast cancer (mBC) by enhancing the care pathway and promoting access to testing for ESR1 and gBRCA mutations.	2 years

Collaborators and Investigators

• Sponsor: European Institute of Oncology

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: December 31, 2024
• First Submitted That Met QC Criteria: December 31, 2024
• First Posted (Actual): January 7, 2025

Study Record Updates

• Last Update Posted (Actual): March 24, 2026
• Last Update Submitted That Met QC Criteria: March 23, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HR+/HER2- BRCA
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Neoplastic Processes; Skin Diseases; Breast Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Breast Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: L2-268

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No