To Identify Primary Resistance to CDK4/6 Inhibitors in Breast Cancer

Enrolled patients will receive first-line treatment with a CDK4/6 inhibitor + AI (anastrozole, letrozole or exemestane) in accordance with local practice. No drugs will be provided by the study Sponsor. Following disease progression on first-line therapy, subsequent, second-line therapy will be administered at physician discretion and as per physician choice. For all participating patients, serum and plasma samples will be collected at the following time-points: * Baseline (\< 2 weeks before treatment) * During treatment with CDK4/6 inhibitors + AI: at day 15 (+/- 2) of the first cycle, day 1 (+/-2) of cycle 2, day 1 (+/- 2) of the cycle closest to the first trial-mandated tumor evaluation (after 12-18 weeks from study inclusion), day 1 (+/- 2) of cycle 6, and every 6 cycles thereafter * At disease progression or permanent discontinuation of CDK4/6 inhibitors + AI (within 35 days from last CDK4/6 inhibitor dosing) * During the immediate subsequent treatment (second line) (any type, as per physician choice): at day 1 (+/- 2) of cycle 1 (if \> 7 days from last CDK4/6 inhibitors dosing), at day 1 of cycles 3, 6 and every 6 cycles thereafter * At disease progression or permanent discontinuation of second line treatment (within 35 days from last dosing) One sample of whole blood will be collected at baseline. All blood samples will be taken concomitantly with blood draws for routine clinical practice. To be eligible for the study, availability of material from one formalin fixed and paraffin embedded (FFPE) tumor block from a baseline biopsy of a metastatic site taken before starting treatment is mandatory. Although not mandatory for inclusion, material from an archival FFPE tumor block from the primary breast tumor must also be provided, whenever available. Additionally, material from one FFPE tumor block of a tissue biopsy from a metastatic site collected upon disease progression to first-line treatment with CDK4/6 in and AI will be collected whenever possible