Benign breast disease and the risk of breast cancer in the next 15 years.

AIM: Fibrocystic mastosis (FCM) is defined by the totality of dystrophic changes of the mammary tissue, the grouping in the form of fibrosis of epithelial, cystic, metaplastic and hyperplastic alterations. A very good estimation of the cancer risk is related specifically to the microscopic aspect. Other factors, the family history as well as the presence of an inherited gene determining the increase in the risk of breast cancer are also considered. But, if a woman known with fibrocystic mastosis has not undergone any biopsy, then it is impossible to calculate the specific individual risk of developing cancer. MATERIAL AND METHODS: The data collected as a study material and considered refer to: the total num- ber of cases investigated and diagnosed with fibrocystic mastosis, the annual distribution of this disease cases, the distribution of the cases according to age groups, admission reasons, clinical examination, personal pathologic history clinically significant for the basic disease (the main diagnosis), the family medical history significant for the basic disease, the anatomopathological diagnosis. RESULTS: Between 2004 and 2006, at "Cuza Voda" Obstetrics and Gynecology Hospital of Iasi, a maximum number of cases is noticed in 2006, when there were 147 cases, and the lowest number of cases was in 2005. There was high frequency of the anatomopathological examinations that highlighted the presence of fibrocystic lesions (both proliferative and non-proliferative), and the second most often diagnosis is fibroadenoma. Though fibrocystic mastosis is not clearly defined, it is still admitted that in order to support this diagnosis it is first compulsory to exclude malignant tumours. CONCLUSIONS: Only in 5% of the women with fibrocystic mastosis cellular changes can be revealed in the form of atypical hyperplasia, which are a risk factor for cancer. The lesion that delimits cancer from non-cancer is ductal carcinoma in situ. An incidence of over 20% is present in the countries that use mammographic screening programmes, mammographic surveillance programmes and programmes for the guided localization of nonpalpable lesions of the mammary gland.

Chemopreventive potential of black cohosh on breast cancer in Sprague-Dawley rats.

BACKGROUND/AIM: This study examines the chemopreventive potential and action of the herb black cohosh on Sprague-Dawley rats. MATERIALS AND METHODS: Female Sprague-Dawley rats were treated with an extract of black cohosh enriched in triterpene glycosides (27%) at 35.7 (Group I), 7.14 (Group II), 0.714 (Group III) or 0 mg/kg b.w. for 40 weeks starting from 56 weeks of age and the incidence of benign and malignant mammary tumors was determined at the end of observation. RESULTS: Among female rats treated at 35.7 and 7.14 mg/kg b.w. there was a dose-related reduction (p<0.05) of the incidence of mammary adenocarcinomas when compared to the treatment of 0.714 mg/kg b.w., with a protection index (calculated relative to the group III; PI=[total tumours × 100 animals of group III] - [total tumours × 100 animals of the group I (or group II)]/ [total tumours of group III] × 100) for mammary adenocarcinomas of 87.5 and 48.8%, respectively. Black cohosh reduced Ki-67 and cyclin D1 protein expression in fibroadenomas, by immunohistochemistry. CONCLUSION: Our results suggest that black cohosh may have chemopreventive potential for mammary cancer.

Effects of raloxifene on normal breast tissue from premenopausal women.

The objective of this study was to evaluate the effects of raloxifene on normal breast tissue. A randomized, double-blind study was carried out in 30 ovulatory, premenopausal women of 18-40 years of age, who had been diagnosed with fibroadenoma of the breast. The patients were divided into two groups: Group A (placebo, n = 16) and Group B (raloxifene 60 mg, n = 14). The medication was given for 22 days, beginning on the first day of the menstrual cycle. An excisional biopsy was carried out on the 23rd day during which a sample of normal breast tissue was collected to evaluate the presence of the proliferating cell marker Ki-67. Student's t-test was used for the statistical analysis of data (p < 0.05). Mean percentage of stained nuclei in groups A and B was 10.96 +/- 1.27 and 1.21 +/- 0.26, respectively (p < 0.001). Raloxifene significantly reduced the proliferative activity of normal breast tissue in premenopausal women.

[Study of an antioxidant dietary supplement "Karinat" in patients with benign breast disease]. / Izuchenie antioksidantnoi biologicheski aktivnoi dobavki k pishche "Karinat" u bol'nykh s fibroadenomatozom molochnykh zhelez.

A randomized double blind placebo-controlled trial of efficiency of a dietary supplement "Karinat" in patients with benign breast disease was carried out. Karinat contains beta-carotene 2.5 mg, alpha-tocopherol 5 mg, ascorbic acid 30 mg and garlic powder 150 mg per one tablet. Out of 66 patients, 33 patients were given karinat, 33 were given placebo. The patients reccived a tablet of karinal or placebo twice a day during 6 months. Examinations of the patients included clinical estimation of symptoms of mastopathy and dysalgomenorrhea, breast sonography and mammography. It was found that karinat reduced the severity of mastalgia, premenstrual syndrome, dysmenorrhea and algomenorrhea and caused regression of palpable symptoms of the breast fibromatosis. On the whole karinat had positive action in 75.8% that was significantly greater by 45.5% as compared with placebo. Karinat may be useful for the treatment of patients with benign breast disease.

Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium.

The anticarcinogenic effects and mechanisms of the biotechnological drugs of Panax ginseng C.A. Meyer cultivated in Russia, bioginseng, panaxel and panaxel- 5, were studied. Bioginseng was produced from a tissue culture of ginseng root cultured on standard medium, whereas panaxel and panaxel-5 were produced from ginseng tissue root cultures using standard mediums enriched with 2-carboxyethylgermanium sesquioxide and 1-hydroxygermatran-monohydrate respectively. All three ginseng drugs inhibited the development of mammary tumors induced by intramammary injections of N-methyl-N-nitrosourea (MNU) in rats, the development of the brain and spinal cord tumors induced by transplacental administration of N-ethyl-N-nitrosourea (ENU) in rats, and the development of uterine, cervical and vaginal tumors induced by intravaginal applications of 7,12-dimethylbenz(a)anthracene (DMBA) in mice. The ginseng drugs induced the cytotoxic activity of macrophages in mice, enhanced T-lymphocyte rosette formation in guinea pigs exposed to cyclophosphamide, and stimulated the production of thyroid hormones in rats. These mechanisms may contribute to the anticarcinogenic action of the ginseng drugs. The organic germanium compounds present in panaxel and panaxel-5 did not potentiate the anticarcinogenic or immuno- stimulatory effects as much as biogeinseng. Preliminary clinical trials with panaxel and bioginseng were carried out in patients with precancerous lesions of the esophagus and endometrium. Panaxel was found to have a strong therapeutic effect in patients suffering from chronic erosive esophagitis. Bioginseng induced the regression of adenomatous-cystic hyperplasia of the endometrium in some patients. Thus, we conclude that the drugs of ginseng appear to hold considerable promise for future cancer chemoprevention.

Effect of a half dose of tamoxifen on proliferative activity in normal breast tissue.

OBJECTIVES: To investigate the proliferative activity of the mammary gland epithelium and plasma levels of progesterone, estradiol, prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and sex hormone-binding globulin (SHBG) in premenopausal women treated with 10 and 20 mg of tamoxifen (TAM) for 22 days. PATIENTS AND METHODS: A randomized double-blind study was performed with 43 premenopausal women with a diagnosis of fibroadenoma of the breast. The patients were divided into three groups: A (n = 15, placebo); B (n = 15, TAM 10 mg/day) and C (n = 13, TAM 20 mg/day). They started taking an oral dose of TAM or placebo on the very first day of the menstrual cycle. Lumpectomy was performed on the 22nd day of therapy. Normal breast tissue samples were collected during surgery, immediately immersed in 10% buffered formalin, processed for routine histology and immunohistochemistry for proliferating cell nuclear antigen (PCNA) detection. Two peripheral blood samples were collected, both on the 22nd day of the menstrual cycle, in order to evaluate the hormone levels. PCNA expressing epithelial cells were quantified by using a digital program Kontron Image System KS-300 in 1000 cells (400 x ). RESULTS: The percentage of cells expressing PCNA was significantly higher in the group receiving placebo (group A, 50.3%) when compared to groups receiving TAM 10 or 20 mg/day (group B, 24.1%; and group C, 23.2%, respectively) (P < 0.001). Differences between groups B and C were not significant. Levels of progesterone, estradiol and SHBG were significantly higher in B and C groups compared to group A. Increasing concentrations of FSH (P < 0.0045) and lower levels of prolactin (P < 0.0055) were only found in the group receiving 20 mg/day of TAM (group C). CONCLUSIONS: A 22-day TAM therapy, either with 10 or 20 mg/day, significantly reduced the PCNA expression and therefore the proliferative activity of the normal human breast tissue. Increasing levels of estradiol, progesterone and SHBG were associated with TAM therapy at 10 or 20 mg/day. However, a significant change of the level of FSH and prolactin was reached only with a 20-mg/day dose.

[The goals and possibilities of drug therapy in mastopathies (results of a questionnaire addressed to oncologists in various regions of Russia)]. / Zadachi i vozmozhnosti lekarstvennogo lecheniia i dispanserizatsii bol'nykh mastopatiei (rezul'taty oprosa onkologov raznykh regionov Rossii).

The results of a questionnaire-based investigation involving 126 oncologists who treat mastopathy are presented. The study failed to establish any significant decrease in breast cancer morbidity as a result of treating mastopathy by medication. It was found that the whole problem of treatment and follow-up of dibraodenoma mammae needs to be re-considered.

Chemoprevention of 2-amino-1-methyl-6-phenylimidazo[4,5-b]-pyridine (PhIP)-induced mammary gland carcinogenesis by antioxidants in F344 female rats.

Chemopreventive effects of the antioxidants 1-O-hexyl-2,3,5- trimethylhydroquinone (HTHQ), 3-O-ethylascorbic acid (EAsA), 3-O-dodecylcarbomethylascorbic acid (DAsA), green tea catechins (GTC) and ellagic acid on 2-amino-1-methyl-6- phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in female F344 rats. Groups of 20-21 6-week-old rats were maintained on a powdered diet containing 0.02% PhIP alone, PhIP together with 0.5% HTHQ, 1% EAsA, 1% DAsA, 1% GTC or 0.1% ellagic acid, these antioxidants alone or basal diet alone without supplement for 52 weeks. The survival rates of PhIP plus antioxidant groups at the end of the experiment were higher than that of the PhIP alone group. Sequential observation of palpable mammary tumors demonstrated only one tumor by week 52 in the PhIP plus HTHQ group, whereas 40% of the rats receiving PhIP alone had tumors by this time point. The final incidence of mammary adenocarcinomas was significantly decreased in the PhIP plus HTHQ group (4.8%, P < 0.01) as compared to the PhIP alone value (40%). Although statistically not significant, incidences of adenocarcinomas in the other antioxidant-treated groups (23.8-28.6%) were also lower than in the PhIP alone group. Furthermore, the incidence of large intestinal tumors in the PhIP plus HTHQ group (0%) showed a tendency to decrease relative to the PhIP alone group (16.7%). These results indicate that antioxidants, particularly HTHQ, exert a potent chemopreventive action against PhIP-induced carcinogenesis.