[Menopausal hormonal therapy and breast cancer.]

The most common treatment for menopausal syndrome is menopausal hormone therapy (MHT), however, the safety of MHT, due to the risk of developing and recurrent breast cancer (BC), is still a matter of debate. The review presents the results of randomized cohort studies of this issue. It has been shown that MHT increases the risk of developing of breast cancer and disease recurrence after treatment. Risk of breast cancer developing in women getting MHT, depends on body mass index (BMI), duration of hormone use and dose of drugs, and is greater in thin women comparing with women with increased BMI, and also greater in estrogen-progestin combined MHT users comparing with estrogen-only users. It was found that in women using MHT hormone-dependent forms of cancer developed more often, but by the time of diagnosis, disease was found in more advanced stage and metastases in lymph nodes were found more often comparing with patients who did not use MHT. Risk of breast cancer recurrence is less with the use of low doses of vaginal estrogen. An alternative option for the relief of menopausal disorders in breast cancer patients during and after treatment is using of pineal gland hormone melatonin, since, along with its anti-aging properties, it is able to suppress cancer at the stages of initiation, progression and metastasis and has the ability to reduce the toxic effects of anticancer drugs while increasing their effectiveness.

Possibilities of estimating the prognosis for development of preinvasive cervical neoplasia by the latest molecular biology methods.

Secondary prevention of cervical cancer is the identification and treatment for preinvasive forms of the disease, which include cervical intraepithelial neoplasia (CIN). The traditional method of identification of CIN is cytological however the sensitivity and specificity of this method is limited. The efficacy of a test for human papillomavirus as well as new molecular-biological methods for assessing the prognosis of development of dysplasia and choice of appropriate treatment tactics are still in the process of discussion. The article contains information about different possibilities of using molecular-biological methods for assessing the prognosis of development of CIN and cervical cancer.

[Possibilities of antiviral and immunomodulatory therapy for patients with preinvasive cervical neoplasia].

Secondary prevention of cervical cancer is the identification and treatment of preinvasive forms of the disease, which include dysplasia or cervical intraepithelial neoplasia. Traditional surgical treatment of preinvasive neoplasia does not always result in elimination of the virus that, in its turn, cannot completely exclude the possibility of recurrence. The article presents references and own observations on possibilities of drug therapy in complex treatment for cervical neoplasia.

[Ian Vladimirovich Bokhman and the St. Petersburg School of Oncogynecology].

The article describes the history of the formation of the St. Petersburg school of oncogynecology based at the Department of Oncogynecology of the N. N. Petrov Research Institute of Oncology since 1927 until the present day. The contribution of the Heads of this Department is characterized in the creation of the St. Petersburg school of oncogynecology for the period of its existence. A brief biography of Professor Y. V. Bokhman is presented who has made the most significant contribution to the development of domestic oncogynecology. The main scientific directions of the Department of Oncogynecology are discussed in historical aspect.

[Prevalence of gynecological cancer and survival of patients].

The article presents an analysis of the situation with cancer in the world, Russia and more detailed (database of the Population-based Cancer Registry) in St. Petersburg. It is presented medium-term morbidity of the population of St. Petersburg per cervical cancer, endometrial cancer and ovarian neoplasms. The use of geoinformation systems allowed presenting incidence (standardized indicators) by districts of the town.

[Effectiveness of the model used for screening and early diagnosis of cervical cancer in Karelia].

The article presents the results of a study of the dynamics of morbidity and mortality from cervical cancer among women in Karelia and detection rate of cancer in situ of the cervix during cytological screening in various areas of Karelia from 1998 to 2012. It is shown that cervical cancer incidence in Karelia for this period increased 3 times more. At the same time it is marked an increase of the level of cervical cancer early diagnosis by increasing the detection rate of the disease in Stages I-II from 66.1% to 77.4% and also an increase in the detection rate of preinvasive cervical cancer from 24.3% in 1998-2002 up to 62.8% in 2008-2012. On the example of Kondopoga region of Karelia it is showed that to ensure early diagnosis of cervical cancer in 95% it is necessary a coverage of the female population at least 70%. This coverage can be achieved by establishing a state program of organized cytological screening for cervical cancer.

[Prognostic value of human papilloma virus DNA test in patients surgically treated for squamous cell cervical cancer].

The human papilloma virus (HPV) DNA test was performed in paraffinized biopsy samples of iliac lymph nodes obtained from 98 patients with cervical cancer receiving therapy in N. N. Petrov Research Institute of Oncology in 2000 to 2007. The data obtained was compared to patients clinical course. The HPV DNA was detected in 29 of 98 patients samples (29,6%), 27 of those patients had metastatic disease. These patients had significantly higher metastasis rate than HPV DNA-negative patients (p < or = 0,05). The following highly oncogenic genotypes of HPV DNA were detected: type 16 in 15 patients (51,72%), type 18 in 4 patients (13,79%), type 31 in 5 patients (17,24%) and type 33 in 5 patients (17,24%). In all the cases the HPV type detected in the lymph nodes corresponded to the one detected in the primary tumor. The relapse-free survival of HPV DNA-positive patients with iliac lymph nodes metastases (N1) was significantly lower than in HPV DNA-negative patients (p < or = 0,05). The iliac lymph nodes HPV DNA detection had 43,6% sensitivity (95% CI: 28/60%) and 79,7% specificity (95% CI: 67/89%) for relapse prediction. The test results had diagnostic value in 65,3% of cases, the test was false-negative in 56,4% and false-positive in 20,3% of cases.

[Human papilloma virus and lymphatic metastasis in squamous cell carcinoma of the cervix].

Our study included 112 patients with squamous cell cervical carcinoma la-lib stages (FIGO). All of them were restaged on the basis of histological evidence after surgical treatment. Ninety-eight were staged at final analysis. Human papilloma virus (HPV) was detected in endocervical smears and paraffin blocks of lymph nodes by PCR and real-time PCR. Oncogenic HPV in primary tumor was detected in 86 (87.8%); two or more genotypes--65 (75.58%): still more--21 (24.4%). In the latter group, the frequency of regional lymph node metastases was significantly higher. HPV DNA was identified in iliac lymph nodes in 29 (26.6%); 27 of them had metastases to those nodes. HPV in DNA which was significantly more frequent in involved lymphocytes may be used as marker. Since our method for early detection of metastases to regional lymph nodes is highly specific, it may be recommended as a diagnostic procedure.

[The role of Ki-67, mutant suppressor gene p53 and low mitotic levels in defining the prognosis for adult granulosa cell tumor of the ovary].

Clinico-morphological examination of adult granulosa cell tumors of the ovary was carried out in 17 patients (mean follow-up duration--146.2 +/- 22.16 months). Overall and relapse-free survival appeared significantly higher in low expression of Ki-67 (8.63 +/- 1.4%), mutant suppressor gene p53 (3.55 +/- 1.9%) and low mitotic levels in tumor (2.33 +/- 0.9 per 10 fields of microscope) (p < 0.05).

[Frequency of infertility in endometrial cancer]. / Chastota besplodiia pri rake éndometriia.

A retrospective study included 1,559 patients with endometrial carcinoma who had received surgical and combined treatment (1968-1995). It was found that infertility was at the background of practically all cases under the age of 30 (92.3%). Moreover, high rates of infertility were discovered in the histories of patients with light-cell (mesonephroid) carcinoma which developed in menopause.

[Effect of neoadjuvant therapy with neovir on the level of steroid hormone receptors in endometrial cancer tissue]. / Vliiane neoad''iuvantnoi terapii neovirom na soderzhanie retseptorov steroidnykh gormonov v tkani raka tela matki.

The effects of neoadjuvant therapy with neovir, provera and their combinations on endometrial tumor morphology, progesterone (PR) and estradiol (ER) receptor levels were studied in 50 patients, aged 40-78, with primary tumors stage I-III, and without concomitant pathology. A 19-day course of neovir did not alter tumor morphological status but was followed by a significant rise in PR and ER concentrations. After neoadjuvant therapy in combination with provera, which generally lowers cytoplasmic receptor levels, mean values of receptors dropped in PR+ tumors while, in PR- tumors, they increased significantly. Our findings suggest that neovir may be used in clinic to stimulate endometrial tumor sensitivity to specific hormonal therapy, particularly, for hormone-independent neoplasia.

[Peroxidase activity in human uterine tissue: connection with clinico-morphological features of endometrial cancer]. / Aktivnost' peroksidazy v tkani tela matki cheloveka: sviaz' s kliniko-morfologicheskimi osobennostiami raka éndometriia.

Peroxidase activity was determined in 98 patients with endometrial cancers. In 34 patients with endometrial cancers, the activity of the enzyme was also detected in the neighbouring unchanged (normal) tissues. It was shown that in tumor tissues the level of peroxidase activity was higher than in normal ones. The peroxidase activity increased both in tumor and normal endometrium when clinical and morphological characteristics of tumor were unfavourable, i.e. at later stages of the disease, deeper invasion to myometrium, lower levels of differentiation of tumors. The peroxidase activity was somewhat higher in post-menopausal women; however, no direct was found between the activity of this enzyme in malignant and normal tissues, on the one hand, and the menstrual status of patients with different clinical and morphological characteristics of endometrial cancer, on the other relationship. The level of peroxidase activity in normal and malignant tissues was more pronounced in advanced and poorly-differentiated tumors. It seems important to use peroxidase activity as a prognostic factor and as a possible marker of endometrial cancer hormone-dependence that needs further investigation.

[The potential and feasibility of conservative therapy for the early stages of ovarian canceri]. / Vozmozhnosti i predely organosokhraniaiushchego lecheniia raka iachnikov.

Improvement in techniques of early diagnosis of ovarian cancer (OC) has highlighted the importance of development of methods of conservative surgery. Numerous researchers have failed so far to reach consensus on working out strategies of treatment. A retrospective analysis of clinico-morphological data on 176 patients with bordar-line and OC stage I (conservative surgery--46; radical--130) (1980-1985) showed that efficacy depended on tumor pattern rather than method of treatment. Given high risk of recurrence in unremoved ovary (2 out of 28 reproductive females), bilateral salpingo-oophorectomy without removal of the uterus is discussed as an alternative procedure of conservative therapy. Modern procedures of this therapy requiring accurate staging and monitoring can be carried out at large medical centers only.

[Primary multiple neoplasm of the endometrium and adjuvant hormone therapy in patients with breast cancer]. / Pervichno-mnozhestvennyi rak èndometriia i ad'iuvantnaia gormonoterapiia u bol'nykh rakom molochnoi zhelezy.

The contribution made by adjuvant hormone therapy in the development of primary multiple endometrial adenocarcinoma (EA) in patients with breast tumors (BT) is not quite clear. The study was based on the data on 5,790 cases of BT treated at our Clinic and 4,447 females screened for hormone-dependent neoplasms. Patients with BT were found to be at high cumulative risk for endometrial carcinogenesis caused by general factors of risk and pathogenesis. The risk was particularly high in BT (stage 1) within 12 months after treatment. There was no correlation between tamoxifen treatment and significant increase in EA frequency. Promotion of tumor proliferation by tamoxifen was identified in endometrial tissue in 62 patients with BT. This may facilitate clinical manifestations of another latent EA in such patients. Dynamic surveillance of the endometrium and ovary should include ultrasonography of pelvic organs and cytologic examination (smears) of the ecto- and endocervix and endometrial aspiration biopsy.

Estrogen content and DNA unwinding in tumor and normal endometrial tissue of aging endometrial cancer patients.

Over the past years, data on the role of DNA damage in hormonal carcinogenesis have been accumulated. In 21 endometrial cancer (EC) patients (mean age 61.8 +/- 1.6 years), no difference between malignant and normal endometrium in estradiol content (radioimmunological assay) and in alkali-induced DNA unwinding as a measure of DNA strand breakage (fluorometrical assay) was discovered. At the same time (contrary to normal endometrium), there were no correlations between the estradiol content in malignant endometrium with DNA unwinding or blood estrogen level. The estradiol concentration in malignant endometrium increases with age in menopausal EC patients, though no correlation between estrogen content in endometrial tissue and body weight was discovered. DNA unwinding rate in malignant endometrium correlates only with the concentration of steroid receptors in normal endometrial tissue. It may be possible that before the appearing of any neoplastic changes in the endometrium, a higher level of estradiol in the target tissue leads to DNA damage which may be considered as a factor predisposing to tumor development. Practically speaking this would mean that the estradiol content and DNA unwinding level in endometrial tumors may be used in future as indicators for therapeutic intervention (first of all, during the hormone therapy of EC) and also as markers for the evaluation of the effectiveness of the latter.

[Pathogenetic variation of uterine cervix tumors]. / Patogeneticheskaia neodnorodnost' raka sheiki matki

Variation in pathogenetic pattern was suggested on the basis of an evaluation of biological and tumor-related factors carried out in 505 patients with primary cervical tumors, stage I-III. Clinical course and prognosis appeared to be in correlation with the variation.

[Multifactorial analysis of the effect of metabolic and endocrine factors on cellular immunity in patients with cancer of the uterine body]. / Mnogofaktornyi analiz vliianiia metabolicheskikh i éndokrinnykh faktorov na kletochnyi immunitet u bol'nykh rakom tela matki.

Multifactorial analysis of effects of metabolic and endocrine determinants of the host and morphology of the tumor on cellular immunity has been undertaken in 29 patients with cancer of the corpus uteri. Several regression models obtained using the Hocking-Leslie method demonstrated significant effects of age, obesity, triglyceride levels, morphologic differentiation of the tumor and magnitude of invasion on various levels of cellular immunity, presenting as an increase in T-helper and decrease in suppressor counts. The multifactorial analysis depicted additive effects of endocrine homeostatic determinants and the tumor on different aspects of cellular immunity in cancer of the corpus uteri.