<br>        Inclusion Criteria:<br><br>          1. Post- or pre/peri-menopausal female patients, age =18 years<br><br>          2. Patients with metastatic or locally advanced (non-operable) breast cancer disease<br><br>          3. Patients who are appropriate candidates for aromatase inhibitor + palbociclib<br>             combination therapy OR Patients having already received endocrine therapy who are<br>             appropriate candidates for fulvestrant+ palbociclib combination therapy<br><br>          4. Patient has not received treatment for locally advanced or metastatic disease OR<br>             Patient has received one prior line of chemotherapy and/or a maximum of two endocrine<br>             therapy lines for locally advanced or metastatic disease<br><br>          5. Peri-/pre-menopausal patients should additionally receive a GnRH-agonist..<br><br>          6. The tumor must be hormone-receptor positive<br><br>          7. The tumor must be HER2-negative defined as either HER2 immunohistochemistry Score 0 or<br>             1+ or as HER2-negative by in situ hybridization..<br><br>          8. Eastern Cooperative Oncology Group (ECOG) performance status 0-2<br><br>          9. Adequate organ and marrow function before palbociclib treatment starts on C1D.<br><br>         10. In case of patients of child bearing potential: negative pregnancy test (urine or<br>             serum) at baseline. Patients must agree to use highly effective non-hormonal<br>             contraception<br><br>         11. Resolution of all acute toxic effects of prior therapy, including radiotherapy grade<br>             <1 (except toxicities not considered a safety risk for the patient) and recovery from<br>             surgical procedures<br><br>         12. Signed Written Informed Consent<br><br>         13. Willingness and capability to use CANKADO<br><br>         14. Availability of hardware: Computer and/or tablet and/or smartphone with internet<br>             access<br><br>        Exclusion Criteria:<br><br>          1. Known hypersensitivity to aromatase inhibitor, fulvestrant, palbociclib or any of its<br>             excipients<br><br>          2. Contraindication for aromatase inhibitor, fulvestrant or palbociclib; or GnRH-agonists<br>             (if pre-menopausal)<br><br>          3. Prior treatment with any inhibitor of cyclin dependent kinase (CDK).<br><br>          4. Patients with locally advanced or metastatic, symptomatic, visceral spread, who are at<br>             risk of life threatening complications in the short term<br><br>          5. Known active uncontrolled or symptomatic central nervous system metastases<br><br>          6. Current use of food or drugs known to be potent inhibitors or inducers of Cytochrome<br>             P450 3A4 (CYP3A4)<br><br>          7. High cardiovascular risk, including, but not limited to recent myocardial infarction,<br>             severe/unstable angina, or severe cardiac dysrhythmias in the past 6 months of<br>             enrollment<br><br>          8. Diagnosis of any second malignancy within the last 5 years prior to enrollment, except<br>             for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ<br>             of the cervix<br><br>          9. Participation in other clinical trials involving investigational drug(s) (Phases 1-4)<br>             within 2 weeks before the current study begins and/or during study participation<br><br>         10. Lactating women<br><br>         11. Life expectancy < 3 months<br><br>         12. Known infection with HIV, hepatitis B virus, or hepatitis C virus<br><br>         13. Concurrent severe, uncontrolled systemic disease, social or psychiatric condition that<br>             might interfere with the planned treatment and with the patient's adherence to the<br>             protocol<br><br>         14. Legal incapacity or limited legal capacity.<br>