Aromatase inhibitors are drugs used in the treatment of breast and ovarian cancer in women. Their action is based on blocking the influence of hormones that stimulate the development of the disease. What is worth knowing about these drugs? When are aromatase inhibitors used?
Aromatase inhibitorsare used in adjuvant therapy after chemotherapy, radiation therapy, or surgery. Preparations of this nature can also be used for pharmacological prophylaxis of breast cancer.
How do aromatase inhibitors work?
The action of aromatase inhibitors is based on blocking the synthesis of estrogens. These hormones stimulate the development of hormone-dependent tumors of the breast and ovary. By reducing the concentration of these substances, the development of lesions is inhibited.
Aromatase is an enzyme responsible for the conversion of androgens, i.e. hormones that determine male characteristics. Thanks to this transformation, estrogens are produced in the body. Aromatase inhibitors block this process. Ultimately, this reduces estrogen synthesis, leading to a therapeutic effect.
This method of cancer treatment is called hormone therapy.
Aromatase inhibitors as hormone therapy for cancer
Hormone therapy can be used at various stages of the neoplastic disease. It is often used as an adjunct treatment to therapy with other drugs. It is also used as a preoperative treatment, as well as a therapeutic method in generalized neoplastic disease, i.e. in which metastases have appeared.
The goal of hormone therapy in the treatment of breast cancer is to overcome the stimulating effect of estrogens on cancer cells. Aromatase inhibitors block the synthesis of these hormones in the following areas of the body:
- ovaries
- adipose tissue
- endometriosis lesions
Mechanism of action of aromatase inhibitors
Some types of breast cancer express estrogen receptors. For such tumors, estrogens act as a growth stimulant. This type of cancer is hormone-dependent.
After the menopause, the ovaries stop producing oestrogens, but they are still formed in the adrenal glands from androgens with the help of aromatase. Additionally, the presence of this enzyme within the mammary gland contributes to contactneoplastic lesion with estrogens. Aromatase can also be found in adipose tissue, muscles and liver.
Aromatase inhibitors attach to aromatase, deactivating it. As a result, the process of conversion of androgens into estrogens is blocked. The concentration of these hormones in the body decreases, and neoplastic changes are not stimulated to grow.
Aromatase inhibitors are not generally used to treat breast cancer in premenopausal women. This is because during the fertile period of the patients' fertile life, a decrease in estrogen levels activates the hypothalamus and the pituitary axis to increase the secretion of gonadotrophins. This in turn leads to stimulation of the ovaries. The consequence of this stimulation is the increased production of androgens.
Increased levels of gonadotropins also stimulate the synthesis of aromatase. Increased synthesis of this enzyme with a simultaneous high concentration of androgens increases the level of estrogens. This mechanism works in the opposite way to an aromatase inhibitor, which leads to a lack of therapeutic effect.
Breakdown of aromatase inhibitors
Aromatase inhibitors are divided into two basic groups:
- steroidal aromatase inhibitors
- non-steroidal aromatase inhibitors
One of the steroidal aromatase inhibitors is exemestane. This drug binds to the active site of the enzyme aromatase. Thus, it irreversibly blocks its activity. The drug is used in premenopausal and postmenopausal women for the treatment of breast cancer.
NSAIDs bind reversibly to the enzyme. These drugs inhibit the synthesis of estrogens by as much as 90%. They are characterized by a strong therapeutic effect and specificity for a specific enzyme. This means that they do not disturb the synthesis of other hormones, which reduces side effects. This group includes anastrozole and letrozole.
Drugs from this group are used in:
- in postmenopausal women in the adjuvant treatment of hormone-dependent early breast cancer
- in postmenopausal women on extended adjuvant therapy for hormone-dependent breast cancer after standard treatment for 5 years
- in postmenopausal women for the treatment of hormone-dependent breast cancer for whom chemotherapy is not an appropriate regimen when immediate surgery is not needed
- in the treatment of hormone-dependent advanced breast cancer in postmenopausal women,
- in postmenopausal women in the treatment of hormone-dependent advanced breast cancer after previous hormone therapy followed by relapse or progression of the disease
Scheme of using inhibitorsaromatase
Aromatase inhibitors are typically used in combination therapy with tamoxifen. This type of hormone therapy usually lasts 10 years.
Tamoxifen is also an anti-estrogen drug. However, its mechanism of action is different. Due to this difference in mode of action, cancer cells that have acquired resistance to tamoxifen continue to be sensitive to aromatase inhibitors.
The most common application patterns are:
- 5 years tamoxifen, then 5 years aromatase inhibitor
- 5 years aromatase inhibitor, then 5 years tamoxifen
- 2-3 years tamoxifen followed by 5 years aromatase inhibitor
- 5 years aromatase inhibitor
Toxicity of aromatase inhibitors
Aromatase inhibitors are preparations of low toxicity compared to other anti-cancer drugs. They can be used safely for many years of treatment.
Specific to aromatase inhibitor therapy are the side effects of the locomotor system. Osteoarticular pain occurs in 20-50% of treated women. Due to the blockage of estrogen production by this group of drugs, there is a decrease in bone density due to decalcification. As a result, the risk of fractures increases.
The use of drugs from this group may also trigger:
- thromboembolic complications
- episodes of central nervous system ischemia
- hot flashes
- genital bleeding
It should be noted, however, that these side effects after administration of aromatase inhibitors occur much less frequently than after administration of tamoxifen.
About the author
Sara Janowska, MA in pharmacyPhD student of interdisciplinary doctoral studies in the field of pharmaceutical and biomedical sciences at the Medical University of Lublin and the Institute of Biotechnology in Białystok. A graduate of pharmaceutical studies at the Medical University of Lublin with a specialization in Plant Medicine. She obtained a master's degree defending a thesis in the field of pharmaceutical botany on the antioxidant properties of extracts obtained from twenty species of mosses. Currently, in his research work, he deals with the synthesis of new anti-cancer substances and the study of their properties on cancer cell lines. For two years she worked as a master of pharmacy in an open pharmacy.
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