Identification of Risk Factors for Brain Recurrence in Patients With HER2-positive Localised Breast Cancer (CRANIUM)

HER2 gene amplification, detected in 20% to 30% of breast cancers, was a poor prognostic factor before the advent of anti-HER2 therapies. In the early 2000s, trastuzumab revolutionised the management of patients with HER2-positive (HER2+) breast cancer in the metastatic and localised stages of the disease.

At the time of diagnosis of metastatic disease, 7-11% of patients have brain metastases, with (70% of cases) or without symptoms (30% of cases). In the absence of brain metastases, 30% to 50% of patients will develop brain metastases within the first two years of treatment, depending on whether the disease is hormone receptor positive (HR+) or negative (HR-).

The presence of brain metastases is the most important prognostic factor. The neurological symptoms caused by the presence of these lesions, but also by the local treatments offered, affect patients' quality of life, although improvements in surgical and radiotherapy techniques have significantly reduced the need for particularly toxic whole brain radiotherapy.

International guidelines do not recommend systematic brain MRI in the absence of neurological symptoms, either in the adjuvant or metastatic stages of this disease. However, there may be a role for more systematic and earlier screening for cerebral recurrence, as single cerebral recurrences without extracranial involvement are common and the new anti-HER2 agents (i.e. tucatinib, an anti-HER2 tyrosine kinase inhibitor, and T-Dxd) have shown significant objective response rates in cerebral metastases.

To date, no clinical or histological prognostic factor (proliferation index, HR expression, etc.) has been used to identify a population of patients at high risk of cerebral relapse, allowing monitoring and treatment to be personalised.

New tools for these indications would significantly modify our clinical practice, allowing the identification of a subpopulation at high risk of cerebral recurrence, suitable for increased monitoring and therapeutic adjustment.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Breast Cancer
• Intervention / Treatment: Other: Pre-treatment biopsy

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Valérie JOLAINE, Dr; Phone Number: +33 (0)299253036; Email: v.jolaine@rennes.unicancer.fr
• Study Contact Backup: Name: Marion TROCHET; Phone Number: +33 (0)299253165; Email: m.trochet@rennes.unicancer.fr

Study Locations

• France
  • Rennes, France, 35 000
    • Recruiting
    • Centre de lutte contre le cancer Eugène Marquis
    • Contact: Fanny LE DU, Dr
    • Principal Investigator: Fanny LE DU, DR

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

women with HER2+ non-metastatic breast cancer treated at the CRLCC Eugène marquis

Description

Inclusion Criteria:

• Age ≥ 18 years old
• be a female patient
• Patients with histologically proven HER2-positive invasive breast cancer (IHC 3+ or 2+ with positive SISH),
• Neoadjuvant chemotherapy and intra-tumour clips indicated at the multidisciplinary consultation meeting (RCP).
• Signed Informed Consent Form

Exclusion Criteria:

• pregnant or breast-feeding women
• Have had a haematoma requiring level II analgesics at the time of the diagnostic biopsy.
• Known coagulation disorders
• Individual deprived of liberty or placed under the authority of a tutor, or a currator
• Not be affiliated to a social security regimen

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HER positive; The study will include an initial assessment and longitudinal and individual follow-up to identify the occurrence of clinical events of interest and to monitor the evolution of any tumour biomarkers on circulating tumour DNA.	Other: Pre-treatment biopsy; A breast biopsy is performed just before the "clip" is placed in the tumour and additional blood samples are performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptomic profile change of HER2+ primary breast tumours before any treatment	comparison of the transcriptomic profile of HER2+ primary breast tumours before any treatment of patients who will develop brain metastases within 5 years with patients who will not develop them	At inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcriptomic profile change on circulating tumour DNA (ctDNA)	High-throughput sequencing (NGS) of a panel of genes previously identified by transcriptomic analysis	At baseline, Year 1; Year2; Year3, Year4; Year 5, at relapse

Collaborators and Investigators

• Sponsor: Center Eugene Marquis
• Investigators: Principal Investigator: Fanny LE DU, Dr, Centre de lutte contre le cancer Eugène Marquis

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2024
• Primary Completion (Estimated): June 6, 2031
• Study Completion (Estimated): June 6, 2031

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 10, 2024

Study Record Updates

• Last Update Posted (Actual): August 1, 2025
• Last Update Submitted That Met QC Criteria: July 31, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Biopsy; Central Nervous System; Metastases
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Skin Diseases; Breast Diseases; Recurrence; Breast Neoplasms
• Other Study ID Numbers: 2023-4-1-001

Drug and device information, study documents

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