Aromatase inhibitors given all clear

17 Apr 2008

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.

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+); about 75% of breast cancers.

Many trials have shown AIs to be more effective than tamoxifen, the gold standard for ER+ tumours, however concerns have been raised about their effects on the cardiovascular system: The consequences of oestrogen deprivation are known to be atherosclerosis, high levels of fat in the blood, high cholesterol levels and consequent heart problems.

In a study presented at the 6th European Breast Cancer Conference in Berlin, Dr Alain Monnier, head of the medical oncology department at the Belfort-Montbéliard Hospital, France, looked at the results from several trials of AIs in order to compare the effects versus tamoxifen and placebos on lipid levels and heart problems.

His team found that there was no increase in cholesterol levels with AI use, only a decrease with tamoxifen:

"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."

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

In trials that compared AIs with tamoxifen, increases were seen in heart-related problems, but in another trial (MA.17), which compared letrozole with placebo, there were no differences in cholesterol levels or other cardiovascular problems.

"These results show that when compared with tamoxifen, adjuvant AI therapy has been associated with an increased incidence of high cholesterol, 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.

He also explained that the frequency of fatal heart attacks in the adjuvant AI trials was no more than that of women of the same age without breast cancer. This suggests that AIs do not increase the incidence of fatal cardiovascular complications, but lack the cardioprotective effects of tamoxifen.

Dr. Monnier emphasised the superiority of AIs over tamoxifen for preventing breast cancer recurrence and the potentially fatal toxicities associated with tamoxifen such as venous thromboembolism (VTE) and endometrial (lining of the uterus) cancer.

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.