Minimally interventional study on prevalence of emerging ESR1 mutations in liquid biopsy in three cohorts of patients with breast cancer (with and without prior therapies in metastatic setting, and during first-line aromatase inhibitor plus CDK4/6 inhibitor therapy) in comparison with patient's baseline ESR1 mutation status as defined by tissue profiling.
BC patients, male and female,
18 years old and older,
Pre or post menopausal,
With HR+ (ER and/or PR positive) and Her-2 negative (confirmed centrally),
Patients WITHOUT HR+ (ER- and/or PR-positive)/HER2-negative disease,
Patients without radiological and/or pathological confirmation of locally unresectable and/or metastatic breast cancer,
Patients who are NOT candidates for further systemic treatment following a diagnosis of metastatic disease or disease progression,
Patients who have already started a CDK4/6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) for first-line metastatic disease (for Cohort 1);
3 parallel cohorts: 1. Locally advanced/metastatic HR-positive/HER2-negative breast cancer, either treatment-naïve or having previously received adjuvant therapy, without prior palliative therapy, eligible for first-line hormonal therapy, with primary tumour tissue available; 2. Locally advanced/metastatic HR+/HER2- breast cancer, progression during treatment with hormone therapy plus a CDK inhibitor; with primary tumour tissue available; 3. Locally advanced/metastatic HR+/HER2- breast cancer, with no disease progression during 6 months of hormonal therapy plus a CDK4/6 inhibitor; with archived tumour tissue available. Patients will be enrolled from the start of therapy with AI plus CDK4/6i in the metastatic setting (index date) up to 6 months into this first-line therapy, provided they have no clinical or radiological evidence of progressive disease. Patients will be followed up until disease progression.
Cohort
Prospective
Not listed
Prevalence of emerging ESR1 mutations
Primary objective A (Cohorts 1 and 2): to determine the prevalence of emerging ESR1 mutations in liquid biopsy samples from two cohorts of breast cancer patients (with and without prior treatment in the metastatic setting) and to compare this with the baseline ESR1 mutation status as determined by the patient's tissue profile. Primary objective B (Cohort 3): to determine the overall prevalence of emerging ESR1 mutations during first-line treatment with AI plus CDK4/6i in patients without clinical or radiological evidence of progressive disease, using a highly sensitive ctDNA assay.
Define the prevalence of PIK3CA, AKT1, PTEN, BRCA1, BRCA2, PALB2, ERBB2 mutations.
To determine the prevalence of mutations in PIK3CA, AKT1, PTEN, BRCA1, BRCA2, PALB2 and ERBB2 in liquid biopsy samples and compare these with the patient's baseline status. To determine the prevalence of ESR1 mutations at different time points during treatment with AI plus CDK4/6i; to validate a highly sensitive and specific ctDNA assay for common ESR1 variants using πCode technology (PlexBioTM).
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