a prospective, randomized multicenter, open-label comparison of preoperative trastuzumab emtansine (t-dm1) with or without standard endocrine therapy vs. trastuzumab with standard endocrine therapy given for twelve weeks in patients with operable her2+/hr+ breast cancer within the adapt protocol.

Conditions: Breast Cancer

Summary: trial to optimize neoadjuvant therapy for her overexpression and co-expressing of hormone receptors(er and/or pr) breast cancer (her2+/hr+). a new high potential trastuzumab conjugate t-dm1(trastuzumab was linked with the cytotoxic agent mertansine dm1)was tested with endocrine therapy and without against a standard arm with trastuzumab and endocrine therapy.

the neoadjuvant therapy patients with her2+/hr+ (her2+ and er+ and/or pr+) tumor will receive single agent t-dm1 for 12 weeks (3,6 mg/kg q3w) with or without standard endocrine therapy (tamoxifen in premenopausal women and an aromatase inhibitor in postmenopausal women, if not contraindications are present, in a standard daily dosage). the control group will receive trastuzumab in 3-weekly schedule (8 mg/kg as loading dose and then 6 mg/kg q3w) in combination with the same standard endocrine therapy, if no contraindications are existent.

Eligibility criteria:
inclusion criteria: * female patients, age at diagnosis 18 years and above (consider patients at 70 years and above for adapt elderly) * histologically confirmed unilateral primary invasive carcinoma of the breast * clinical t1 - t4 (except inflammatory breast cancer) * all clinical n (cn) * no clinical evidence for distant metastasis (m0) * known hr status and her2 status (local pathology) 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 start of induction treatment in premenopausal patients * 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 additional inclusion criteria for participation in the her2+/hr+ sub-protocol: * confirmed er and/or pr positive and her2+ by central pathology * clinical ct1c - t4a-c (participation of patients with tumors \>ct2 is strongly recommended) * all clinical n (participation of patients with cn0, if ct1c is strongly recommended) * patients must qualify for neoadjuvant treatment * lvef \> 50%; lvef within normal limits of each institution measured by echocardiography and normal ecg (within 42 days prior to induction treatment) 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 after consultation with the sponsor * concurrent treatment with other experimental drugs. participation in another clinical trial with any investigational not marketed drug within 30 days prior to study entry * male breast cancer * concurrent pregnancy; patients of childbearing potential must implement * a highly effective (less than 1% failure rate) non-hormonal contraceptive measures during the study treatment * breast feeding woman * sequential breast cancer * reasons indicating risk of poor compliance patient not able to consent additional exclusion criteria for participation in the her2+/hr+ sub-protocol: * known polyneuropathy ≥ grade 2 * severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study * inadequate organ function (e.g. hepatic impairment, pulmonary disease, etc.) * uncompensated cardiac function (current unstable ventricular arrhythmia * requiring treatment, history of symptomatic chf nyha classes ii-iv), history of myocardial infarction or unstable angina pectoris within 6 months of enrollment, history of severe hypertension, cad - coronary artery disease) * severe dyspnea * pneumonitis 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