[Effectiveness of aromatase inhibitors in comparison with metformin for neoadjuvant treatment in patients with endometrial cancer].

We compared the efficacy of endometrial cancer neoadjuvant treatment in 38 patients receiving nonsteroid (letrozol, anastrozol) or steroid (ekzemestan) aromatase inhibitors and 12 patients receiving metformin. The changes in glucose metabolism were revealed in 26.3% of patients treated with aromatase inhibitors and 16.7% of patients treated with metformin. However, comparison of endometrial thickness (M-echo signal) data, postoperative data on favorable differentiation grade changes rate and proliferative activity (Ki-67 expression) revealed the superiority of 2-4 weeks aromatase inhibitors course in comparison with 2-9 (average 5.3 +/- 0.7) weeks metformin treatment.

[Criteria for evaluating the effectiveness of aromatase inhibitors in the neoadjuvant treatment of patients with endometrial carcinoma].

Clinical and experimental effects of neoadjuvant treatment of endometrial cancer patients with non-steroidal aromatase inhibitors: letrozole (femara, n=10, 2.5 mg/day, 14 days), anastrozole (arimidex, n=15,1 mg/day, 28 days) and exemestane (aromazine, n=13, 25 mg/day, 14 days) were compared. Administration of anastrozole was mostly frequently followed by pain relief in the lower abdomen and/or decreased rates of uterine discharge. Endometrial wall thickness (M-echo signal) decreased significantly in 60% of patients receiving anastrozole, exemestane - 58.3% and letrozole - 40%. Substantial drop in intratumoral aromatase and blood estradiol levels occurred more frequently after anastrozole and letrozole while progesterone receptor levels in tumor were markedly lower after exemestane administration. Assay of blood LH (except letrozole), FSH and cholesterol appeared to be of less relevance. On the contrary, significance of assessment of marker Ki-67 expression, which, in the case of anastrozole, dropped in 6 out of 12 patients after a 28-day course, could hardly be underestimated.

[Comparison of letrozole and exemestane used in non-adjuvant therapy of endometrial carcinoma].

The clinical and endocrine-related effects of 2-week preoperative treatment of endometrial carcinoma patients with a non-steroid inhibitor of letrozole aromatase (femara 2.5 mg/day, n=10) and a steroid inactivator of the enzyme (exemestane 25 mg/day, n=13) were compared. In the first group, pain relief in the lower part of the belly and/or decreased uterine discharge were reported in two cases, as well as a 31% drop in the mean endometrial M-echo (ultrasound) signal. In the exemestane group, two patients revealed moderate uterine discharge decrease matched by a 15.6% decrease in M-signal intensity; no tumor was detected in another patient on completion of the course. Letrozole effect was relatively greater when such parameters as tumor-tissue aromatase level, estrogen concentration in vaginal smear and blood-cholesterol, FSH and LH levels were taken into consideration. However, exemestane therapy involved a relatively sharper drop in the levels of tumor receptors of progesterone and a significantly higher estrogen/progesterone receptor ratio. Hence, no matter how short treatment duration was, both steroid and non-steroid aromatase inhibitors induced effects predominantly associated with lowering estrogen production in endometrial carcinoma patients. This makes a case for further clinical trials of these drugs to deal with the pathology.

[Tumor tissue aromatase and estrogen levels versus clinical course of endometrial cancer]. / Aktivnost' aromatazy, tkanevoe soderzhanie éstrogenov i osobennosti techeniia raka éndometriia.

Levels of aromatase, a key enzyme in estrogen biosynthesis, were assayed in tumor tissue sampled from 25 patients with endometrial cancer. In addition, estradiol concentrations were compared in normal and altered endometrial tissue from 78 patients suffering uterine cancer. Unlike breast cancer, aromatase was not detectable in altered endometrium unless tissue estrogens could be identified in both normal and tumor tissue. Hence, aromatase presence served as an indicator of malignant transformation. Its concentration in samples of uterine tissue varied 0-28.4 fM/mg protein/hr (an average of 12.9(1.7 fM/mg protein/hr). There was hardly any correlation between this level, on the one hand, and menopause and body mass, on the other. Yet, it tended to increase in step with stage of disease and cell differentiation decline. Estradiol concentrations in malignant endometrium in both reproductive and menopausal patients were higher than in macroscopically normal ones, while still cycling women tended to show higher values than menopausal ones. Although there was no significant difference in estradiol levels in the altered endomentrium of patients with pathogenetical patterns of uterine cancer stage I and II, they did show a direct correlation with clinical stage of tumor process and depth of invasion into the underlying myometrium. Hence, unlike estrogens circulating in blood, those contained in tissue ("intratumor") ones did enhance the aggressiveness of endometrial cancer course. It will be for further investigations to show whether it is due to an estrogen fraction being carried away by tumor from the circulation, or estrogens being synthesized by aromatase in tumor itself.

[Neoadjuvant use of the aromatase inhibitor letrozole in uterine cancer: endocrine and clinical effects]. / Neoad''iuvantnoe primenenie ingibitora aromatazy letrozola pri rake tela matki: éndokrinnye i klinicheskie éffekty.

Endometrial cancer (EC) is estrogen-dependent tumor in the hormonal treatment of which mostly progestins are used. During last 5-7 years feasibility of aromatase inhibitors use in EC is discussed without any special practical move in this direction. To evaluate possible biological response of tumor and patients to such treatment, we conducted a short pilot study involving 10 primary postmenopausal EC patients, mostly stage Ia,b (average age 59) who received letrozole (Femara, Novartis) 2.5 mg/day during 14 days before operation. Clinical, sonographical, morphological, cytological and hormonal-metabolic (blood estradiol, FSH, LH, glucose, lipid fractions by RIA or enzyme-colorimetric methods; tumor progesterone receptors by LBA and aromatase activity by 3H-water release assay) studies were included into the protocol before and after treatment. Tolerability of letrozole was satisfactory in all patients. 2 patients reported decrease of pain and pathological secretions from uterine cavity. In 3 patients, decrease in M-sonographical endometrial signal was registered; average value after treatment was 31.1% lower than before it. Tendency to the decrease in estrogenicity of vaginal smears was revealed. Average decrease in blood estradiol was 37.8% and in progesterone receptor level and aromatase activity 34.4% and 17.5% respectively. Decrease of aromatase activity in tumor tissue was registered mostly in normal weight patients. A more detailed and longer randomized study of aromatase inhibitors in EC performed in neoadjuvant setting deserves consideration.