In postmenopausal women, estrogen is produced
through aromatase, an enzyme that converts hormone precursors into estrogen. Aromatase inhibitors prevent androgen
from being converted into estrogen in postmenopausal women, thereby blocking
estrogen’s ability to activate can-cer cells; limiting the amount of estrogen
means that less estrogen is available to reach cancer cells and make them grow.
There are two types of aromatase inhibitors.
Type 1, or steroidal, inhibitors
include exemestane; type 2, or nonsteroidal,
inhibitors include anastrozole and letrozole.
Aromatase inhibitors are taken orally (in pill
form) and are usually well tolerated. Steady-state plasma levels after daily
doses are reached in 2 to 6 weeks. Inactive metabolites are excreted in urine.
inhibitors work by lowering the body’s production of estrogen. In about
one-half of all patients with breast cancer, the tumors depend on estrogen to
grow. Aromatase inhibitors are used only in postmenopausal women because they
lower the amount of estrogen that’s produced outside the ovaries, such as in
muscle and fat tissue. Because these drugs induce estrogen depri-vation, bone
thinning and osteoporosis may develop over time.
Type 1 inhibitors, such as exemestane,
irreversibly inhibit the aro-matase enzyme, whereas type 2 inhibitors, such as
anastrozole, re-versibly inhibit it. Type 1 aromatase inhibitors may still be
effec-tive after a type 2 aromatase inhibitor has failed.
Anastrozale and letrozole work by competitively
binding to heme of the cytochrome P450 subunit of aromatase, leading to
de-creased levels of estrogen in all tissues; they don’t affect synthesis of
adrenocorticosteroids, aldosterone, or thyroid hormones.
Aromatase inhibitors are primarily used to treat
postmenopausal women with metastatic breast cancer. They may be administered
alone or with other agents such as tamoxifen.
Certain drugs may decrease the effectiveness of
anastrozole, in-cluding tamoxifen and estrogen-containing drugs. (See Adversereactions to aromatase inhibitors.)