Evaluating the Effect of Candesartan vs Placebo in Prevention of Trastuzumab-associated Cardiotoxicity

Inclusion Criteria:

* Women aged ≥18 years
* WHO: ≤ 2
* Strongly HER2-positive breast cancer, defined as an immunohistochemistry score of 3+ using the HercepTestTM, or gene amplification by fluorescence in situ hybridization, or chromogenic in situ hybridization (CISH).
* Serum creatinine \<140 umol/l or creatinine clearance \> 50 ml/min (by Cockcroft-Gault formula)
* Thyroid stimulating hormone between 0.5-3.9 MU/l
* Blood pressure systolic ≥ 140 mmHg and diastolic ≥ 90 mmHg is acceptable at randomization. However prior to the first administration of trastuzumab blood pressure should be regulated and should be systolic ≥ 100 mmHg and ≤ 180 mmHg and diastolic ≥ 60 mmHg and ≤ 100 mmHg. (blood pressure should be regulated according to the guidelines of appendix 5)
* LVEF ³ 50% assessed by multigated angiography (MUGA) or cardiac ultrasound
* Adjuvant regimen: trastuzumab start ≥ 3 weeks after day 1 of the last anthracycline chemotherapy cycle
* Trastuzumab treatment according to standard medical care
* Written informed consent to participate in the study

Exclusion Criteria:

* Prior anthracycline chemotherapy regimen or anti-HER2 therapy, or other prior biologic or immunotherapy for breast cancer treatment or any malignancy
* Previous malignancy requiring chemotherapy or radiotherapy
* Uncontrolled serious concurrent illness
* Patients with New York Heart Association (NYHA) class II/III/IV congestive heart failure
* Myocardial infarction \< 6 months before randomization
* Treatment with ACE inhibitor, ATII blocker, or lithium. Patients treated with ACE inhibitor, or ATII blocker can switch (after randomization and during the chemotherapy period) to alternative antihypertensive therapy; see appendix 5.
* History of hypersensitivity to the study medication
* Pregnancy or breast feeding