Aromatase inhibitors are drugs used to treat postmenopausal women with breast cancer.  The aromatase inhibitors currently used in cancer treatment are considered “third-generation” ones: anastrozole (Arimidex®), exemestane (Aromasin®), aminoglutethimide (Cytadren®) , 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 respond to estrogen, including most breast cancers.  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 contrast, the estrogen in premenopausal women is primarily produced by the ovaries.  Aromatase inhibitors have no effect on this type of estrogen production, and these drugs are not given to the 11 percent of breast cancer patients who are premenopausal.  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.  Aromatase inhibitors are not given to patients with triple-negative breast cancer; these tumors do not have the receptors for estrogen or progesterone.

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 if the cancer cells have estrogen receptors.  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.  Trials experimenting with aromatase inhibitors to treat ovarian cancer also show positive results, but the drugs are not widely used for this purpose. 

Tamoxifen was long the standard for treatment of ER+ breast cancer.  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.  While in the past aromatase inhibitors were used to prevent recurrence of cancer, now they are often also used as part of the primary chemotherapy regimen.

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.  There are four aromatases currently approved.

Letrozole

Brand/Trade Names: Femara

Manufacturers: Novartis Pharma Stein AG, AASraw Biochemical Technology Co., Actavis Inc.,   Alcami,   Apotex Pharmachem Inc.

Formula: C₁₇H₁₁N₅

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes: Approved by the FDA in 1997.  Used for treatment of breast cancer.

Exemestane

Brand/Trade Names: Aromasin

Manufacturers: Pharmacia & Upjohn Company, AASraw Biochemical Technology Co., AMRI,  Apotex Pharmachem Inc.,  Cipla

Formula: C₂₀H₂₄O₂

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:  Approved by the FDA in 1999.  Used in treatment of breast cancer.

Anastrozole

Brand/Trade Names: Arimidex

Manufacturers: AstraZeneca Pharmaceuticals LP, AASraw Biochemical Technology Co.,  Alcami,   Apotex Pharmachem Inc.,   Aspen Biopharma Labs Pvt

Formula: C₁₇H₁₉N₅

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:  Approved by the FDA in 1995.  Used in treatment of breast cancer.

Aminoglutethimide

Brand/Trade Names: Cytadren

Manufacturers: Novartis Pharma Schweizerhalle AG, ChemGenix Laboratories Pvt Ltd

Formula: C₁₃H₁₆N₂O₂

Mechanism: Aromatase Inhibitor

Class: Hormone Suppressant

Administration: Oral

Notes:  Approved by the FDA in 1980.  Used for treatment of breast cancer and prostate cancer.