Study to Compare Neoadjuvant Combination of Trastuzumab and Pertuzumab With Concurrent Taxane Chemotherapy or Endocrine Therapy and Quality of Life Assessment Under Adjuvant Therapy in Operable HER2+/HR+ Breast Cancer Patients

Inclusion criteria

• Female patients, age at diagnosis 18 years and older
• Histologically confirmed unilateral primary invasive carcinoma of the breast
• Patients must qualify for neoadjuvant treatment as follows:

• No clinical evidence for distant metastasis (M0)
• Clinical cT1c-T4a-c (participation of patients with tumors > cT2 is strongly recommended) and no evidence for distant metastases (M0)
• All clinical N (participation of patients with cN+, also in case of cT1c, is strongly recommended)
• Known positive HR-status and centrally confirmed HER2+-status by IHC/FISH
• Patients need to fulfill adequate blood count and organ function to receive chemotherapy (see exclusion criteria).
• Tumor block available for central pathology review
• Performance Status ECOG ≤ 1 or KI ≥ 80%
• Negative pregnancy test (urine or serum) within 7 days prior to registration in premenopausal patients
• Patients of childbearing potential must accept to implement a highly effective (less than 1% failure rate according to Pearl index) non-hormonal contraceptive measures during the study treatment and for 6 months following the last dose of study treatment (trastuzumab and pertuzumab) such as:

• Intrauterine device (IUD)
• bilateral tubal occlusion
• vasectomised partner
• sexual abstinence
• Written informed consent prior to beginning specific protocol procedures, including expected cooperation of the patients for the treatment and follow-up, must be obtained and documented according to the local regulatory requirements
• The patient must be accessible for treatment and follow-up
• LVEF > 55%; LVEF within normal limits of each institution measured by echocardiography (within 42 days prior to randomization)
• Normal ECG (within 42 days prior to randomization)

Exclusion criteria

• Known hypersensitivity reaction to the compounds or incorporated substances
• Prior malignancy with a disease-free survival of < 10 years, except curatively treated basalioma of the skin, pTis of the cervix uteri
• Non-operable breast cancer including inflammatory breast cancer
• Previous or concurrent treatment with cytotoxic agents for any reason
• Concurrent treatment with other experimental drugs and participation in another clinical trial or clinical research project within 30 days prior to study entry is excluded
• Male breast cancer
• Concurrent pregnancy
• Breastfeeding
• Sequential breast cancer
• Reasons indicating risk of poor compliance
• Known polyneuropathy ≥ grade 2
• Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to:

• Uncompensated chronic heart failure or systolic dysfunction (LVEF < 55%, CHF NYHA classes II-IV),
• unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block,
• Angina pectoris within the last 6 months requiring anti-anginal medication,
• Clinically significant valvular heart disease,
• Evidence of myocardial infarction on electrocardiogram (ECG),
• Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mm Hg).
• Inadequate organ function including but not confined to:

• hepatic impairment (Child Pugh Class C)
• pulmonary disease (severe dyspnea at rest requiring oxygen therapy)
• Abnormal blood values:

• Thrombocytopenia > CTCAE grade 1
• Increases in ALT/AST > CTCAE grade 1
• Hypokalaemia > CTCAE grade 1
• Neutropenia > CTCAE grade 1
• Anaemia > CTCAE grade 1