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) and 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 female,
* 18 years old and older,
* pre or post menopausal,
* With HR+ (ER and/or PR positive) and 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.
Cohort 3:
* BC Patients,
* Male and female,
* 18 years or older,
* pre- or post-menopausal,
* With HR+ (ER and/or PR positive), HER2-negative (centrally confirmed) locally advanced unresectable and/or metastatic disease,
* Confirmation of HR and HER2 status may be performed on the primary tumour or the metastatic lesion (patients with discordant results may be included),
* Patients must be on first-line hormonal therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (with or without ovarian suppression) for at least 6 months,
* No clinical or radiological evidence of progressive disease,
* Patients may have received a prior line of chemotherapy in the metastatic setting; however, prior endocrine therapy in the metastatic setting is not permitted,
* Patients may have received chemotherapy in the neoadjuvant/adjuvant setting,
* Patients may have received endocrine therapy (with or without ovarian suppression) in the neoadjuvant/adjuvant setting,
* Patients may have received a CDK4/6 inhibitor in the adjuvant setting, provided they are still eligible for CDK4/6 inhibitor therapy in the metastatic setting,
* Patients must be able to undergo a liquid biopsy procedure before starting their first-line treatment,
* All patients must read and sign an Informed Consent Form.
Exclusion Criteria:
* 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);
* Patients who have already started a new line of treatment for metastatic disease following progression on a CDK4/6 inhibitor in combination with endocrine therapy (with or without ovarian suppression) (for Cohort 2);
* Patients with any suspicion of clinical or radiological disease progression at the time of the first liquid biopsy collection (for Cohort 3),
* Patients who are NOT able to undergo a liquid biopsy procedure,
* Patients who are NOT able to provide informed consent.
