Breast cancer drug relaxes arteries in men with heart disease

A drug used to treat breast cancer has been shown to improve blood flow in men with coronary artery disease. The Cambridge research team who conducted the novel study also demonstrated that the drug reduced cardiovascular risk factors in men (previous research showed that this was the case for women who were administered tamoxifen as a breast cancer treatment).

The researchers studied 31 men with coronary artery disease (CAD). Sixteen were treated with tamoxifen for 56 days and 15 were untreated. The CAD patients were also treated with two common treatments for coronary artery disease: aspirin and cholesterol-lowering drugs known as statins. Ten men who had chest pain (angina), but normal coronary arteries, were also treated with tamoxifen for comparison with the men with CAD.

In the most striking effect, tamoxifen counteracted the toll of ageing on arteries' ability to expand in response to increased blood flow.

"Other studies have shown that the blood vessels' ability to dilate usually declines with age," says Professor Metcalfe, of the Department of Biochemistry. "The average dilation for a man under age 40 is about seven per cent, declining to about 3.5 per cent at 63 years of age - near the average age of the CAD patients in this study. Tamoxifen made the CAD patients' vessels more responsive, somehow overcoming the age-related decline in vessel dilation."

In men with CAD, the vessel dilation increased from 2.1 per cent at the start of the study to 7.5 per cent after 28 days of tamoxifen treatment. In the group with normal coronary arteries, it rose from 3.8 percent to 7.9 percent.

Reduced cholesterol levels also improve vessel dilation. Because CAD patients took cholesterol-lowering drugs as well as tamoxifen, their cholesterol was further lowered.

"However, while tamoxifen did reduce cholesterol levels, the effects on vessel dilation seemed to go beyond that of cholesterol-lowering alone, suggesting some new mechanism," says Professor Metcalfe. He notes that tamoxifen even improved dilation in the men without artery disease who were not taking statins.

In addition, the cholesterol-lowering effects of statins and tamoxifen seem additive, he says.

"This strongly suggests that combined therapy with the two classes of drugs can be considered and is likely to provide additive benefits," Professor Metcalfe says.

Intriguingly, researchers say, tamoxifen also significantly reduced the blood fat known as triglycerides in men, although it causes a slight increase in triglycerides in women. Excess calories, particularly those from carbohydrates, are converted to triglycerides and transported to fat cells to be stored. Hormones regulate the release of triglycerides from fat tissue to meet the body's energy needs between meals.

Professor Metcalfe stresses that it is too soon to say whether tamoxifen should be used to treat CAD in men. Although tamoxifen caused no side effects in this study, a much larger trial to study safety and efficacy is required before SERMs could be considered for treatment of coronary artery disease. Such a trial, the Raloxifene Use for the Heart (RUTH), is currently under way in 10,000 women, he says.