Prevalence of Emerging Treatment-induced Mutations in Metastatic ER-positive Breast Cancer.

Inclusion Criteria: Cohort 1: * BC patients, male and female, 18 years old and older, pre or post menopausal, with HR+ (ER and/or PR positive), Her-2 negative (confirmed centrally) locally advanced irresectable and/or metastatic disease * Confirmation of HR and Her-2 status may be performed in the primary tumor or in the metastatic lesion (patients with discordant results may be included) * Patients must be candidates to CDK4/6i therapy in combination with endocrine therapy in the first line setting (with or without ovarian suppression) * Patients may have received one previous line of chemotherapy in the metastatic setting, but no endocrine therapy in the metastatic setting is allowed * Patients may have received chemotherapy in the neo/adjuvant setting * Patients may have received endocrine therapy (with or without ovarian suppression) in the neo/adjuvant setting * Patients may have received a CDK4/6i in the adjuvant setting, provided they are still candidates for CDK4/6i therapy in the metastatic setting * Patients must be able to undergo a liquid biopsy procedure before starting their first line treatment * All patients must fill and sign an informed consent form. Cohort 2: * BC patients, male and felame, 18 years old and older, pre or post menopausal, with HR+ (ER and/or PR positive), Her-2 negative (confirmed centrally) locally advanced irresectable and/or metastatic disease who have progressed on a CDK4/6i in combination with endocrine therapy (with or without ovarian suppression) in the first or second line setting * All other non-conflicting inclusion criteria for cohort 1 apply. Exclusion Criteria: Patients with HR+ (ER and/or PR positive) and Her-2 negative disease NOT confirmed centrally * Patients with NO radiologic and/or pathologic confirmed locally irresectable and/or metastatic breast cancer * Patients who are NOT candidates for further systemic treatment after diagnosis of metastatic disease or disease progression * Patients who have already started a CDK4/6i in combination with endocrine therapy (with or without ovarian suppression) for metastatic disease in the first line setting (for cohort 1); and patients who have already started a new line of treatment for metastatic disease after disease progression on a CDK4/6i in combination with endocrine therapy (with or without ovarian suppression)(for cohort 2) * Patients who are NOT able to undergo a liquid biopsy procedure * Patients who are NOT able to provide informed consent.