Table 1 PreCycle—inclusion and exclusion criteria

Post- or pre/peri-menopausal female patients, age ≥ 18 years

Known hypersensitivity to aromatase inhibitor, fulvestrant, palbociclib or any of its excipients

Patients with metastatic or locally advanced (non-operable) breast cancer disease

Contraindication for aromatase inhibitor, fulvestrant or palbociclib; or LHTH-agonists (if pre-menopausal)

Patients who are appropriate candidates for aromatase inhibitor + palbociclib combination therapy

Prior treatment with any CDK inhibitor

Patients having already received endocrine therapy who are appropriate candidates for fulvestrant + palbociclib combination therapy

Patients with locally advanced or metastatic, symptomatic, visceral spread, who are at risk of life threatening complications in the short term

One prior line of chemotherapy and/or a maximum of two endocrine therapy lines for locally advanced or metastatic disease is/are allowed

Known active uncontrolled or symptomatic CNS metastases

Peri-/pre-menopausal patients should additionally receive a LHRH-agonist

Current use of food or drugs known to be potent inhibitors or inducers of CYP3A4

The tumor must be hormone-receptor positive

High cardiovascular risk, including, but not limited to recent myocardial infarction, severe/unstable angina, or severe cardiac dysrhythmias in the past 6 months of enrollment

The tumor must be HER2-negative defined as either HER2 immunohistochemistry score 0 or 1 + or as HER2-negative by ISH

Diagnosis of any second malignancy within the last 5 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix

Eastern Cooperative Oncology Group (ECOG) performance status 0–2

Participation in other clinical trials involving investigational drug(s) (phases 1–4) within 2 weeks before the current study begins and/or during study participation

Tissue of the primary tumor and metastatic lesion for biomarker study if applicable

Lactating women

Adequate organ and marrow function

Life expectancy < 3 months

In case of patients of child bearing potential: negative serum pregnancy test at baseline. Patients must agree to use highly effective non-hormonal contraception

Known infection with HIV, hepatitis B virus, or hepatitis C virus

Resolution of all acute toxic effects of prior therapy, including radiotherapy grade < 1 (except toxicities not considered a safety risk for the patient) and recovery from surgical procedures

Concurrent severe, uncontrolled systemic disease, social or psychiatric condition that might interfere with the planned treatment and with the patient’s adherence to the protocol

Willingness and capability to use CANKADO

Legal incapacity or limited legal capacity

Availability of hardware: computer and/or tablet and/or smartphone with internet access

Signed written informed consent