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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
146
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.
Hôpital Claude Bernard
Metz, France
CHR Metz-Thionville
Metz, France
Centre d'oncologie Gentilly
Nancy, France
Institut Jean Godinot
Reims, France
Polyclinique de Courlancy
Reims, France
Centre Henri Becquerel
Rouen, France
Polyclinique de l'Orangerie
Strasbourg, France
Clinique Saint Anne
Strasbourg, France
CHU Strasbourg
Strasbourg, France
Institut de cancérologie de Lorraine
Vandœuvre-lès-Nancy, France
incidence of ESR1 mutations
Time frame: 1 day
incidence of PIK3CA and AKT1 mutations
Time frame: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients with and without endocrine resistance at enrolment
Time frame: 1 day
prevalence of ESR1, PIK3CA and AKT1 mutations in patients according to mono vs combo therapy.
Time frame: 1 day
prevalence of mutations of other genes of interest included in the panel from the start of treatment to progression or end of follow-up
Time frame: 1 day
ESR1, PIK3CA and AKT1 mutations predictor of progression free survival
Time frame: 1 day
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