NCT03318263

CIrCuLAting Dna ESr1 Gene Mutations Analysis

Monitoring of ESR1, PIK3CA and AKT ctDNA Mutations During Real-life Followup of Patients With Metastatic Breast Cancer Treated With Aromatase Inhibitors

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 146 (actual)
• Sponsor: Institut de Cancérologie de Lorraine · Academic / Other
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The estrogen-dependent nature of breast cancer was first reported in 1896 with the publication of George Beatson's observations on the regression of breast cancer following oophorectomy. Endocrine therapy, targeting ER either directly by selective estrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block estrogen production, remains the mainstay of treatment of hormone-sensitive breast cancer in the adjuvant and metastatic settings. Intrinsic (de novo) and acquired endocrine resistance constitutes an important clinical challenge in the treatment of breast cancer and multiple mechanisms are suspected to underlie the emergence of endocrine resistance. The role of the estrogen receptor (ER), encoded by the ESR1 gene, in normal mammary gland development and the progression of breast cancer is well established. ESR1 mutations, occurring in 10 to 30% of ER-positive metastatic breast cancer resistant to AIs, lead to ligand-independent activation of the ER. For patients treated with AIs, monitoring of circulating tumour DNA (ctDNA) for ESR1, PIK3CA and AKT1 mutations could permit early detection of resistance to AIs as recently reported during 2016 American Society of Clinical Oncology (ASCO) meeting.

Conditions

• Breast Cancer

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	next-generation sequencing (NGS)	ESR1, PI3KCA and AKT extensive exon sequencing will be performed using NGS (Miseq Illumina) at the Biopathology department, Institut de Cancérologie de Lorraine (ISO15189 certified lab). Samples taken at baseline (t0), at progression (tp) and 3 months before progression (tp-3) will be systematically analyzed. The intermediate samples will be stored and kept for additional studies. Follow up assessment will be performed according to prescriber's directions.

Timeline

• Start date: 2017-12-07
• Primary completion: 2022-12-22
• Completion: 2022-12-22
• First posted: 2017-10-23
• Last updated: 2023-08-04

Locations

10 sites across 1 country: France