Anastrozole (CAS: 120511-73-1)

 Anastrozole works by inhibiting the synthesis of estrogen. The patent on Arimidex by

AstraZeneca expired June 2010.

Medical uses

The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial was an international randomised

controlled trial of 9366 women with localized breast cancer who received either anastrozole, tamoxifen,

or both for five years, followed by five years of follow-up. After more than 5 years the group that received

anastrozole had significantly better clinical results than the tamoxifen group. The trial suggested that

anastrozole is the preferred medical therapy for postmenopausal women with localized breast cancer, which

is estrogen receptor (ER) positive. Another study found that the risk of recurrence was reduced 40%, but was

associated with an increased risk of bone fractures. The study concluded that ER positive patients benefited

from switching from tamoxifen to anastrozole in patients who have completed 2 years’ adjuvant tamoxifen.

A more recent trial found that anastrozole significantly reduced the incidence of breast cancer in postmenopausal

women relative to placebo, and while there were side effects related to estrogen deprivation observed, the researchers

concluded that this was probably not related to the treatment. Lead author Jack Cuzick was quoted by the BBC as

saying, “This class of medicine is more effective than previous medicine such as tamoxifen and crucially, it has

fewer side effects,” adding that he thought there was now enough evidence to support offering the medicine.

Mechanism of action

Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition, inhibits the conversion

of androgens to estrogens in peripheraltissues (extra-gonadal).

Side effects

Bone weakness has been associated with anastrozole. Women who switched to anastrozole after two years on

tamoxifen reported twice as many fractures as those who continued to take tamoxifen (2.1% compared to 1%).

Bisphosphonates are sometimes prescribed to prevent the osteoporosis induced by aromatase inhibitors. The

level of circulating estradiol is likely causal here and not the anastrozole itself, and so the dose will determine

likelihood of osteoporosis (estradiol inhibits osteoclasts, which resorb bone).

Usage in men

Anastrozole has been tested for reducing estrogens, including estradiol, in men. Excess estradiol in men can cause

benign prostatic hyperplasia,gynecomastia, and symptoms of hypogonadism. It can also contribute to increased risk

of stroke, heart attack, chronic inflammation, prostate enlargement and prostate cancer. 

Usage in children

Anastrozole may be used off-label in children with precocious puberty, or children with pubertal gynecomastia.

Following the onset of puberty, theepiphyseal plate begins to close due to an increased amount of estrogen production

escaping local metabolism and spreading to the circulatory system.