Anastrozole inhibits the estrogen-dependent growth of breast cancer. The drug is used primarily in postmenopausal women and in men as part of endocrine therapy (antihormone therapy) for estrogen-sensitive breast cancer.
What is anastrozole?
Anastrozole inhibits the estrogen-dependent growth of breast cancer. As a benzyltriazole derivative, anastrozole belongs to the non-steroidal aromatase inhibitor drug class. It is primarily used for adjuvant (supportive) therapy of breast cancer in menopausal and post-menopausal women. The active ingredient inhibits the synthesis of estrogen, which is an important growth factor for the mostly hormone-sensitive cells of a breast carcinoma. In addition to tumor growth, anastrozole reduces the risk of metastasis (spread of tumor cells to the rest of the body) and the risk of recurrence (recurrence of the disease). Although the male organism only possesses or synthesizes estrogen in small quantities, men can also develop breast carcinoma. These are also usually treated with aromatase inhibitors such as anastrozole.
Pharmacologic action
The effect of anastrozole is based on the inhibition of aromatase. Aromatase is an enzyme that catalyzes the conversion of androgens (male sex hormones) to estrogens (female sex hormones). Estrogen promotes tumor growth and metastasis in estrogen-sensitive cancers such as breast cancer. Aromatase inhibitors such as anastrozole interfere with this mechanism by binding to aromatase. The enzyme is inactivated and enzymatic catalysis is prevented. As a result, estrogen levels fall, less estrogen is available to the tumor cells, and growth is slowed. In premenopausal women (before menopause), hormone conversion by aromatase takes place mainly in the ovaries. Aromatases are also found in the liver, adrenal glands and adipose tissue cells. However, since aromatase inhibitors are ineffective in the ovaries, estrogen synthesis cannot be blocked here by anastrozole. During the menopause, aromatase activity in the ovaries is successively discontinued. The aromatase and consequently the estrogen concentration drops considerably here, while it remains the same in the other tissue cells. If breast cancer cells develop that also produce aromatase, additional tumor-promoting estrogen is produced in the body. In tumor cells, adrenal glands, adipose tissue cells, and the liver, aromatases can be blocked by anastrozole, and the growth of estrogen-sensitive tumors can be slowed or stopped accordingly.
Medical application and use
Anastrozole is used in the adjuvant endocrine therapy of estrogen-sensitive breast carcinomas and for the therapy of progressive (advanced) breast carcinoma in postmenopausal women. Studies (e.g. ATAC study 2008) have shown that in postmenopausal women, the use of anastrozole following primary therapy (usually surgery followed by radiotherapy and/or chemotherapy) can reduce the risk of recurrence by an average of 24 percent and prolong disease-free survival by about 15 percent. In addition, adjuvant anti-hormone therapy can prolong the time before distant metastases and contralateral tumors (on the complementary side of the body) appear. In general, two basic treatment strategies are available. First, anastrozole can be applied immediately following surgery (upfront therapy). On the other hand, anastrozole can be applied only after a postoperative two- to three-year therapy with tamoxifen (estrogen receptor modulator) (switch therapy). Due to the still missing studies on the comparability of both strategy approaches, individual decisions are made on which strategy to follow in the context of endocrine therapy. In addition, data are still lacking on the optimal duration of treatment. In many cases, prolonged therapy for 5 years is recommended.
Risks and side effects
Because aromatase inhibitors such as anastrozole do not affect the action of other hormones or enzymes, they are relatively well tolerated. In particular, a side effect of anastrozole therapy is a decrease in bone density with a corresponding increase in fracture risk and accompanying joint pain. To reduce these symptoms, increased intake of vitamin D and calcium is recommended.In patients with an increased risk of osteoporosis, bone density should be determined regularly. Fatigability, shortness of breath, vomiting, nausea, hair loss, skin rash and dry vaginal mucous membranes are other possible side effects of anastrozole therapy. Occasionally, loss of appetite, vaginal bleeding, and elevated blood cholesterol levels may be observed. Therapy with anastrozole is contraindicated before menopause, in cases of pronounced renal dysfunction, and moderate to severe liver disease. Estrogens cancel the effect of anastrozole. Application of estrogen-containing drugs (including vaginal suppositories) should be avoided accordingly.
