Aromatase Inhibitors

Aromatase inhibitors are a category of drugs used to treat postmenopausal women with breast cancer. Trials experimenting with aromatase inhibitors to treat ovarian cancer also show positive results, but the drugs are not widely used for this purpose. The aromatase inhibitors used in cancer treatment nowadays are considered “third-generation” ones: anastrozole (Arimidex®), exemestane (Aromasin®), and letrozole (Femara®).

The drugs work by interfering with the enzyme aromatase, which produces estrogen from androgens in the body through a process called aromatization.  Lower estrogen levels result in slowed growth of cancers that require estrogen to grow including breast cancer.  This is effective in postmenopausal women because most of their estrogen is produced in fatty tissues, such as in the breast, and in some areas of the brain. In this case, the estrogen levels are lowered specifically at the site of the cancer for the most significant effect.  In contrast, the estrogen in premenopausal women is primarily produced by the ovaries.  Aromatase inhibitors have no effect on this type of estrogen production.  In fact, lower estrogen levels in the tissues and the brain can stimulate the ovaries to produce more estrogen, counteracting the drug’s effect.  For this reason, aromatase inhibitors are not typically used on premenopausal women.  However, clinical trials are now underway using aromatase inhibitors in combination with drugs that suppress ovarian activity in premenopausal women.

Does estrogen cause breast cancer?  It is not clear if estrogen is involved in starting tumors, but it definitely accelerates the growth of existing tumors.  That’s why breast cancer survivors – even if they appear cancer-free – are often given aromatase inhibitors.  Microscopic tumors that escape detection may grow into a visible cancer under the influence of estrogen.

Aromatase inhibitors fall into two groups. Steroidal inhibitors bond permanently to aromatase, preventing it from converting androgens to estrogen. Exemestane (Aromasin®) is a steroidal inhibitor.  Anastrozole (Arimidex®) and letrozole (Femara®) are the non-steroidal inhibitors, which instead form temporary bonds with aromatase and compete with androgens for the aromatase needed for conversion to estrogen.

Tamoxifen has long been the standard for breast cancer treatment.  Studies are underway to determine the effectiveness of aromatase inhibitors after or in place of Tamoxifen treatment.  Both types of aromatase inhibitors have shown superior performance to Tamoxifen in clinical trials, enabling women with advanced disease to live longer and stopping recurrences in women made cancer-free.  Large scale studies have shown switching from Tamoxifen to an aromatase inhibitor during the course of treatment will produce superior results to staying on Tamoxifen the whole way.

Another idea doctors have come up with is treating cancer patients with a full treatment of Tamoxifen followed by a full treatment of an aromatase inhibitor.

The most serious side effect associated with aromatase inhibitors is accelerated loss of bone density.  A woman with an already increased risk of developing osteoporosis must weigh that accelerated loss against using a slightly less effective drug like Tamoxifen, which is not associated with this side effect.  Other side effects of aromatase inhibitors include joint problems, hot flashes, muscle or body aches, mild nausea, diarrhea, constipation, and general feelings of illness, weakness, or fatigue




Letrozole

Brand/Trade Names: Femara

Formula: C17H11N5

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:

Exemestane

Brand/Trade Names: Aromasin

Formula: C/sub>20H/sub>24O2

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:

Anastrozole

Brand/Trade Names: Arimidex

Formula: C17H19N5

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:

Aminoglutethimide

Brand/Trade Names: Cytadren

Formula: C13H16N2O2

Mechanism: Adrenal Steroid Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes: