Women treated for breast cancer are at increased risk for cardiovascular disease, including heart failure. In this study, by using magnetic resonance imaging (MRI), the investigators want to assess if heart failure medications such as beta blockers and angiotensin receptor blockers can prevent cardiac dysfunction during early breast cancer therapy.

Breast cancer is one of the most common malignancies in women. Recent progress in the detection and treatment of breast cancer has resulted in survival gains, but a consequence of therapeutic advances is an increasing number of long-term survivors who may be at risk for development of cardiovascular disease. Several studies suggest that women treated for breast cancer may be at increased risk for cardiovascular disease, the probable causes being multi-factorial. Importantly, therapies for breast cancer, including radiotherapy, anti-HER-2 regimens and certain chemotherapeutic regimens, may increase the risk of subsequent cardiovascular disease, including atherosclerotic disease, left ventricular dysfunction, and heart failure.

In the current study we propose to undertake a randomized, placebo-controlled, 2x2 factorial, double-blind trial to assess whether left ventricular dysfunction and/or injury is preventable, completely or partly, by the concomitant administration of the angiotensin receptor blocker (ARB), candesartan, and the beta blocker, metoprolol, during postoperative chemotherapy and radiotherapy.

The proposed study addresses an important clinical problem in a large patient group. Thus, the possibility of preventing cardiovascular side effects of contemporary therapy for breast cancer is important both clinically and scientifically.

Inclusion Criteria:

• Women aged 18-70 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Serum creatinine < 140 μmol/L or estimated creatinine clearance > 60 ml/min (using the modification of diet and renal disease (MDRD) formula)
• Systolic blood pressure >= 110 mgHg and < 170 mmHg
• LVEF >= 50%

Exclusion Criteria:

• Hypotension, defined as systolic blood pressure < 110 mmHg
• Bradycardia, defined as heart rate < 50 b.p.m.
• Prior anthracycline chemotherapy regimen
• Prior malignancy requiring chemotherapy or radiotherapy
• Symptomatic heart failure
• Systolic dysfunction (LVEF < 50%)
• Clinically significant coronary artery disease, valvular heart disease, significant arrhythmias, or conduction delays.
• Uncontrolled arterial hypertension defined as systolic blood pressure > 170 mm Hg
• Treatment with ACEI, ARB or beta-blocker within the last 4 weeks prior to study start
• Intolerance to ACEI, ARB or beta-blocker
• Uncontrolled concomitant serious illness
• Pregnancy or breastfeeding
• Active abuse of drugs or alcohol
• Suspected poor compliance
• Inability to tolerate the MRI scanning protocol