No link between aromatase inhibitors and cardiovascular problems

New evidence has emerged that, contrary to some current fears, aromatase inhibitors (AIs) are not associated with an increased risk of heart problems in women who take them to prevent their breast cancer recurring.

In a study presented (Thursday) at the 6th European Breast Cancer Conference (EBCC-6) in Berlin, the researcher, Dr Alain Monnier, said that this was important and reassuring news for women.

AIs, such as letrozole, anastrozole and exemestane, work by causing severe oestrogen deprivation and, increasingly, they are being prescribed for women whose tumours are positive for the oestrogen receptor (ER+). Several trials have shown that AIs are more effective than tamoxifen – the gold standard for ER+ tumours; however, concerns have been raised about their effects on the cardiovascular system. In particular, the consequences of oestrogen deprivation can be atherosclerosis, high levels of lipids (fats) in the blood (hyperlipidaemia), high cholesterol levels (hypercholesterolaemia) and consequent heart problems.

Dr Monnier, a medical oncologist and head of the medical oncology department at the Centre Hospitalier de Belfort-Montbéliard (Belfort-Montbéliard, France), looked at the results from several trials of AIs in order to compare the effects of AIs versus tamoxifen and placebos on lipid levels and heart problems.

“One of the problems with obtaining clear evidence about the impact of AIs on cardiovascular health is that tamoxifen has cardioprotective effects,” explained Dr Monnier. “Tamoxifen is an anti-oestrogen with known lipid-lowering properties; it has been reported to reduce coronary plaques, C-reactive protein, and is associated with decreases in heart problems such as myocardial infarction. This makes comparisons between AIs and tamoxifen difficult to interpret, and so comparisons between AIs and placebos might indicate better the impact of AIs on cardiovascular health.”

After looking at results from several large trials, he found that in one trial (LEAP), which investigated the use of AIs in healthy postmenopausal women who had never had breast cancer, no significant differences were seen in total cholesterol levels between different AIs. In a second trial (MAP.1) letrozole was associated with a transient decrease in cholesterol levels.

In trials that compared AIs with tamoxifen, increases were seen in heart-related problems, but in another trial (MA17), which compared letrozole with placebo, there were no differences in hypercholesterolaemia or other cardiovascular problems.

“These results show that when compared with tamoxifen, adjuvant AI therapy has been associated with an increased incidence of hypercholesterolaemia, but this is probably due to the lipid-lowering effect of tamoxifen, and there is no significant increase in cardiovascular effects,” said Dr Monnier. “There seems to be little difference in cardiovascular profiles between individual AIs, and the relative increase in cardiovascular events in comparison to tamoxifen is not significant for letrozole, anastrozole or exemestane.

“Furthermore, the frequency of fatal heart attacks in the adjuvant AI trials is comparable with an age-matched population of postmenopausal women without breast cancer. This suggests that AIs do not increase the incidence of fatal cardiovascular complications, but lack the cardioprotective effects of tamoxifen.

“These findings are important and very reassuring about the safety of AIs. AIs are clearly superior to tamoxifen in terms of reducing the risk of breast cancer recurring. Also, we should not forget the life-threatening toxicities associated with tamoxifen therapy such as venous thromboembolism (VTE) and endometrial cancer, which do not appear to be a problem with AIs. While AIs have not demonstrated the lipid-lowering properties of tamoxifen, there is no evidence that a significant worsening of lipid levels occurs with their use.”

He concluded: “More postmenopausal women live free of their breast cancer recurring with AI therapy rather than with tamoxifen therapy. However, in this aging population, an increasing cardiovascular risk competes with cancer recurrence as a cause of mortality.”

Results from two AI trials (FACE and MA.27) are awaited and should provide more information on the impact of AIs on cardiovascular health.