Anticancer drug, estrogen synthesis inhibitor.
Letrozole has an antiestrogenic effect, selectively inhibiting aromatase (the enzyme responsible for estrogen synthesis) through its highly specific competitive binding, a subunit of this enzyme, cytochrome P450 heme. It blocks estrogen synthesis in peripheral and tumor tissues.
In postmenopausal women, estrogens are produced mainly by the enzyme aromatase, which converts androgens synthesized in the adrenal glands (mainly androstenedione and testosterone) into estrone and estradiol.
Daily intake of letrozole in a daily dose of 0.1 – 5 mg causes a decrease in plasma concentrations of estradiol, estrone and estrone sulfate by 75 – 95% of the original content. Inhibition of estrogen synthesis is maintained throughout the treatment period.
When letrozole is used in the dose range of 0.1 to 5 mg, there is no impairment of steroid hormone synthesis in the adrenal glands, the ACTH test does not show impairment of aldosterone or cortisol synthesis. No additional intake of glucocorticoids and mineralocorticoids is required.
Blockade of estrogen biosynthesis does not lead to the accumulation of androgens, which are estrogen precursors. No changes in luteinizing and follicle stimulating hormone plasma concentrations, changes in thyroid function, changes in lipid profile, increased incidence of myocardial infarction and stroke were observed during letrozole use.
Against treatment with letrozole, the incidence of osteoporosis increased slightly (6.9% compared to placebo 5.5%). However, the incidence of bone fractures in patients taking letrozole does not differ from that in healthy individuals of the same age.
Letrozole for women
Letrozole adjuvant treatment in early breast cancer reduces the risk of recurrence, increases disease-free survival to 5 years, and reduces the risk of secondary tumors.
Prolonged adjuvant letrozole treatment reduces the risk of relapse by 42%. A significant benefit in disease-free survival was observed in the letrozole group, regardless of lymph node involvement. Letrozole treatment reduces mortality in patients with lymph node damage by 40%.