Detect V / CHEVENDO (Chemo vs. Endo)

Inclusion criteria:

* Signed, written informed consent in study participation
* The primary tumor and/or biopsies from metastatic sites or locoregional recurrences have been confirmed as HER2-positive (FISH-positive or IHC 3+) and hormone receptor positive breast cancer by histopathology according to local testing
* Metastatic breast cancer or locally advanced BC, which cannot be treated by surgery or radiotherapy only
* Pre- and postmenopausal women are allowed
* No more than two prior chemotherapies for metastatic disease
* No more than two prior anti-HER2 therapies for metastatic disease
* Pertuzumab retreatment is allowed if prior pertuzumab treatment was finished 12 months before
* At least one measurable lesion assessable using standard techniques by Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
* Tumor evaluation according to RECIST version 1.1 has been performed within 4 weeks before randomization based on local assessment
* Age ≥ 18 years
* Standard 12-lead ECG values assessed by the local laboratory:

  * QTcF interval at screening \< 450 msec (using Fridericia's correction)
  * Resting heart rate 50-90 bpm
* Left ventricular cardiac ejection fraction (LVEF) ≥ 50% at baseline (as measured by echocardiogram)
* ECOG Score ≤ 2
* Adequate organ function within 14 days before randomization, evidenced by the following laboratory results below:

  * absolute neutrophil count ≥ 1500 cells/µL,
  * platelet count ≥ 100000 cells/µL,
  * hemoglobin ≥ 9 g/dL,
  * ALT (SGPT) ≤ 2.0 × ULN (≤ 3.0 × ULN in case of liver metastases)
  * AST (SGOT) ≤ 2.0 × ULN (≤ 3.0 × ULN in case of liver metastases)
  * bilirubin ≤ 1.5 × ULN (with the exception of Gilbert's syndrome)
  * creatinine ≤ 2.0 mg/dl or 177µmol/L INR ≤ 1,5
* Patients must have the following laboratory values within normal limits or corrected to within normal limits with supplemets before the first dose of study medication:

  * Sodium
  * Potassium
  * Total calcium
* In case of patients of child bearing potential:

Negative serum pregnancy test at baseline (within 7 days prior to randomization) and agreement to remain abstinent (if it is in line with the preferred and usual lifestyle) or use single or combined non-hormonal contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 7 months after the last dose of study treatment

Exclusion criteria:

Patients will be excluded from the study for any of the following reasons:

* History of hypersensitivity reactions attributed to trastuzumab, pertuzumab, ribociclib or to other components of drug formulation
* Mandatory need for cytostatic treatment at time of study entry based on clinical judgment and national/international treatment guidelines
* Known CNS metastases
* Any 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
* Progression on prior Pertuzumab therapy
* Treatment with Pertuzumab within the last 12 months
* Prior treatment with any mTOR- or CDK4/6-inhibitor
* Treatment with any other investigational agents during trial
* Known hypersensitivity to lecithin (soya) or peanuts
* Life expectancy \< 6 months
* Patients with pre-existing grade ≥2 peripheral neuropathy are excluded from taxane-based chemotherapy
* History of serious cardiac disease, including but not confined to:

  * history of documented heart failure or systolic dysfunction (LVEF \< 50%)
  * high-risk uncontrolled arrhythmias i.e., atrial tachycardia with a heart rate ≥100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block (second degree AV-block Type 2 \[Mobitz 2\] or third degree AV-block)
  * angina pectoris requiring anti-anginal medication
  * clinically significant valvular heart disease
  * evidence of transmural infarction on ECG
  * poorly controlled hypertension (e.g., systolic \>180 mm Hg or diastolic \>100 mm Hg)
  * any other cardiac condition, which in the opinion of the treating physician would make this protocol unreasonably hazardous for the patient
* Dyspnea at rest or other diseases that require continuous oxygen therapy
* Patients with poorly controlled diabetes or with evidence of clinically significant diabetic vascular complications
* Patients with known infection with HIV, hepatitis B virus, or hepatitis C virus
* Male patients
* Pregnant, lactating or women of childbearing potential without a negative pregnancy test (serum) within 7 days prior to randomization, irrespective of the method of contraception used
* Medical or psychological conditions that would not permit the subject to complete the study or sign informed consent
* Participation in another clinical study within the 30 days before registration
* Legal incapacity or limited legal capacity