AURORA: Aiming to Understand the Molecular Aberrations in Metastatic Breast Cancer.

Inclusion Criteria:

1. Female or male ≥ 18 years with diagnosis of locally recurrent/advanced BC not amenableto treatment with curative intent or MBC who have not received more than 1 line ofsystemic therapy (any type) in the metastatic setting. Under protocol 4.0, eligible patients will be limited to locally recurrent/advancedbreast cancer not amenable to treatment with curative intent or MBC with:

• histopathology-confirmed TNBC as defined by ER <1% and HER2 negative followingASCO-CAP guidelines
• ILC (either based on ILC morphology or negative E-cadherin expression confirmedby IHC). Mixed ILC/invasive ductal carcinoma are not eligible for the ILC cohort.
• late relapse BC (any subtype). Late relapse is defined as a patient with aradiologic or histologic confirmation of advanced or MBC relapse > 10 years fromthe primary BC diagnosis.

2. Written informed consent prior to registration into the program.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
4. Availability of primary tumor tissue for research purposes.
5. Patient must have a metastatic lesion accessible for biopsy and must agree with thebiopsy procedure.
6. Up until protocol 3.0, up to 100 patients with bone-only metastasis have beenincluded without a metastatic biopsy, if plasma samples have been collected atscreening, and if the patient met all other eligibility criteria.
7. In protocol 4.0, metastatic tumor biopsies from bone lesions will be acceptedprovided that the chosen site of biopsy was not previously irradiated.
8. Brain tissue is accepted if it is obtained through surgical excision not plannedfor AURORA, but as part of the routine clinical practice.
9. The biopsy of the metastatic lesion must be conducted either at the initial diagnosisof the BC relapse before the initiation of 1st line systemic therapy or at the 1stdisease progression before initiation of a second line systemic treatment. There is norestriction in the type of therapeutic modality considered as 1st line systemictreatment, which can consist of any type of treatment administered after the diagnosisof the advanced BC relapse till the 1st disease progression thereafter.
10. Biopsies obtained during routine clinical practice are accepted if both formalin-fixedparaffin-embedded (FFPE) and Frozen Tissue (FT) blocks were collected concurrentlyfrom the same metastatic lesion and if collected at the pre-specified timelines forAURORA.
11. Availability of a whole blood, serum and plasma samples collected at the time ofscreening.
12. Patient agrees to provide blood samples at regular intervals, from the screening aswell as during the follow-up phase of the program.

Exclusion Criteria:

1. The patient has received more than 1 line of systemic therapy (any type) in themetastatic setting.
2. Patients who have received prior palliative radiotherapy to the only site that isaccessible to biopsy.
3. Presence of severe hematopoietic, renal, and/or hepatic dysfunction, including but notrestricted to albumin < 3 g/dl.
4. Known increased risk of hemorrhage during biopsy procedure, as evaluated by thetreating physician.
5. Previous or current malignancies of other histologies within the last 5 years, withthe exception of in situ carcinoma of the cervix, and adequately treated basal cell orsquamous cell carcinoma of the skin.