Aromatase inhibitors increase risk
of cardiovascular disease in postmenopausal women with breast cancer
Postmenopausal women who take aromatase inhibitors as
a treatment for breast cancer may be at an increased risk for developing cardiovascular
disease, according to the results of a meta-analysis.
These data, presented at the 33rd Annual CTRC-AACR San Antonio Breast Cancer
Symposium, indicate that women presenting with breast cancer treatment who have
risk factors for cardiovascular disease should be considered for a shorter duration
of use of aromatase inhibitors.
"It appears that aromatase inhibitors have a significant increase in cardiotoxic
side effects, such as heart attack, angina and heart failure," said Eitan
Amir, M.D., a senior fellow in the division of medical oncology and hematology
at the Princess Margaret Hospital, Toronto, Canada.
Because some cancers, especially breast cancers, require estrogen to grow and
spread, drugs that block estrogen production are often used to treat the disease.
Tamoxifen blocks the effect of estrogen in breast tissue, whereas aromatase inhibitors
prevent the production of estrogen.
Each class of drugs also have related adverse effects. For example, although
tamoxifen blocks estrogen production in breast tissue, it has the opposite effect
in uterine tissue. Previous research has shown that extended use of tamoxifen
results in a small increase in the risk for endometrial cancer and venous thrombosis.
On the other hand, in December 2008, the Food and Drug Administration added
a warning label to anastrozole, an aromatase inhibitor, which indicated potential
increased risk for heart disease. For this reason, Amir and colleagues conducted
a meta-analysis to determine if this increased risk for heart disease occurred
with the use of any aromatase inhibitor.
The researchers examined data from seven large randomized clinical trials that
compared tamoxifen with aromatase inhibitors in postmenopausal women with early-stage
breast cancer.
Data from the analysis confirmed that any duration of use of an aromatase inhibitor
was associated with a 20 percent higher probability of developing cardiovascular
disease. However, use of aromatase inhibitors also resulted in a reduced risk
for venous thrombosis and endometrial carcinoma.
As a secondary analysis, they determined if switching from treatment with tamoxifen
to aromatase inhibitors had any effect on mortality or adverse effects. Results
showed that the risk for serious adverse effects were similar when aromatase inhibitors
were used as an initial treatment compared with switching to aromatase inhibitors
after treatment with tamoxifen.
"However, it appears from the data - and this is strictly hypothesis-generating
- that if a woman switches from one drug to another, there is a reduction in the
risk from death from causes other than breast cancer," Amir said. "This
potentially suggests that there may be side effects that build up the longer a
woman is on a certain drug, but switching drugs may reduce the side effects."
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