Effects of high-fat diet on incidence of spontaneous tumors in Wistar rats.

In a 2.5-year carcinogenicity study, two groups, both including male and female Wistar rats, were fed two different diets with 4% and 16% fat. In addition to 4% soybean oil, the high-fat diet contained 12% mono- and diglycerides, of which 85% was stearic acid and 13% palmitic acid. There was no difference in food consumption, body weight, weight gain, and longevity between the two groups. A statistically significant increase in the incidence of tumors in the high-fat group was seen in fibroadenoma of the mammae (female, p = 0.05). No statistically significant difference was seen when the incidence of benign mammary tumors (adenomas and fibroadenomas) was combined, just as the overall incidence of mammary tumors (adenomas, fibroadenomas, and adenocarcinomas) was not significantly different between the groups. A statistically significant decrease in the incidence of tumors in the high-fat group was seen in adenoma of the parathyroid gland (male, p = 0.04) and medullary carcinoma of the adrenal gland (male, p = 0.04). Combining the incidence of benign and malignant tumors of the adrenal medulla led to a further increase in the level of significance (p = 0.02). The present study showed that a high-fat diet influenced the tumor incidence in certain organs of rats. However, the overall differences in tumor incidence between rats fed the low- and the high-fat diet are considered marginal. Therefore we were not able to confirm or deny the hypothesis that a high-fat diet promotes the development of cancer. It should be noted that, in our study, fat accounted for about 30% of the total energy in the high-fat diet. This is much below the amount of fat normally found in the western diet but corresponds well to the level recommended for human intake. In addition, the rats fed the high-fat diet did not gain more weight, even though no difference was recorded in food consumption (g/kg body wt) between the groups.

Enlarging fibroadenoma in a postmenopausal woman: case report.

The authors describe mammographic and pathologic evidence of the growth of a fibroadenoma in an 82-year-old obese woman, 44 years after menopause, who had never been treated with hormone therapy. The patient's obesity is hypothesized as the causal factor for increased estrogen levels leading to growth of the fibroadenoma.

Risk factors for fibroadenoma: a case-control study in Australia.

Risk factors for fibroadenoma were examined in a case-control study involving 117 fibroadenoma cases ascertained by a major private pathology laboratory in Adelaide, Australia, between January 1983 and October 1985. For each case a population control was randomly selected from the electoral roll in Adelaide and matched to the corresponding case by sex, age, and socioeconomic grading of area of residence. Another 189 women whose first biopsy for benign breast disease was examined in the same laboratory during the same time period as those of the cases, but did not show evidence of epithelial proliferation, were also included in the study as a biopsy control group. Risk of fibroadenoma was associated inversely with the Quetelet index, but there was no evidence of an association with age at menarche or menopausal status. The risk of fibroadenoma decreased with an increasing number of full-term pregnancies and was increased in association with use of oral contraceptives at an early age (under 20 years); however, these two associations were observed only when cases were compared with the population controls. Alcohol consumption and dietary fat intake were found not to be associated with altered risk of fibroadenoma, while in multivariate analyses, duration of cigarette smoking and daily vitamin C intake were both shown to have inverse associations with risk of fibroadenoma. Although fibroadenoma does share some risk factors with breast cancer, there is insufficient evidence to suggest that it represents a precursor state.

Low-frequency electromagnetic radiation enhances the induction of rat mammary tumors by nitrosomethyl urea.

Low-frequency electromagnetic fields enhance the induction of mammary gland tumors in rats using nitrosomethyl urea. The incidence of tumors depended on the duration of exposure to static (dc) and variable (ac) magnetic fields. Variable magnetic fields induced mammary gland cancer much more frequently than static ones. Apart from increasing the incidence of mammary gland tumors, household low-frequency electromagnetic fields reduced the mean latent period of tumor development and led to predominance of malignant tumors in the exposed animals as compared to controls. Mammary gland tumors developed rarely under the effect of static or variable magnetic fields per se, without preliminary administration of a carcinogen. Household low-frequency electromagnetic fields may potentially present an oncogenic hazard for animals and humans.

Smoking habits and risk of benign breast disease.

The relationship between smoking habits and the risk of benign breast disease (BBD) was analyzed using data from a case-control study conducted between 1981 and 1983 in the greater Milan area, Northern Italy. Cases (n = 288) were women with histologically confirmed BBD (203 dysplasia, 85 benign tumours) referred to the National Cancer Institute of Milan for biopsies. Controls were women (n = 291) seen on selected days for a cytological smear for cervical cancer in outpatient clinics of the same Institute. No consistent association emerged between various indicators of smoking habits (smoking status, number of cigarettes smoked per day, duration of smoking) and the risk of BBD. Compared with never smokers the relative risk (RR) of all BBD combined was 0.7 (95% confidence interval, Cl: 0.4-1.3) in exsmokers, 1.4 (95% Cl: 0.8-2.5) in smokers of less than 10 cigarettes per day, and 1.1 (95% Cl: 0.7-1.7) in smokers of 10 or more cigarettes per day. There was some suggestion that the risk may be below unity post-menopause, but the relative risks for smokers were not statistically different in pre- (RR = 1.2; 95% Cl: 0.8-1.8) and post-menopausal (RR = 0.6; 95% Cl: 0.2-1.7) women. The risk of benign tumours (chiefly fibradenoma) was higher in current smokers, but this finding was not statistically significant (RR = 1.5; 95% Cl: 0.9-2.6) and the highest risks were observed in the strata of lighter smokers and those with shorter duration of smoking. Overall these results fail to support a negative association between smoking habits and benign breast disease.

[Breast fibroadenoma: the morphological characteristics, morphogenesis and prognosis]. / Fibroadenoma molochnoi zhelezy: morfologicheskie osobennosti, morfogenez, prognoz.

Morphology of mammary fibroadenoma (FA) is well studied while this is not the case for its morphogenesis and prognosis. The role of a stromal component in the development of FA is outlined. Immune response in FA is mainly directed to the fibroblasts. Further studies of mammary FA will allow one to reveal the biological properties of this tumour and to evaluate adequately its prognosis as in 0.5-2% of cases it undergoes malignant transformation.

[The effect of low-frequency electromagnetic fields on the development of experimental mammary tumors]. / Vliianie nizkochastotnykh élektromagnitnykh polei na razvitie éksperimental'nykh opukholei molochnoi zhelezy.

The paper discusses the effect of low-frequency electromagnetic fields on the development of nitrosomethylurea-induced breast cancer in rats. The occurrence, mean latency period and morphological pattern of breast malignancy was shown to depend upon duration of exposure to variable and static magnetic fields.

Benign breast tumours in an African population.

A detailed prospective clinical study of 238 women presenting with benign breast swellings in the South Eastern equatorial rainforest of Nigeria clearly shows that 94% of lesions were due to two disorders, fibroadenomas and bacterial infections, and that they affected mostly young women in the peak of their reproductive life. Fibroadenoma which accounted for disease in no less than 69% of the women was multiple in 8%, bilateral in 11%, and was considered giant in size in 5% of the cases; by contrast, fibroadenosis was rare, accounting for swellings in only eight patients. Bacterial infections, chronic pyogenic mastitis and tuberculosis together caused breast swellings in 25% of the women studied. In tropical Africa, multiple chronic discharging sinuses suggest tuberculosis of the breast.

Ovarian fibrosarcoma associated with Maffucci's syndrome.

Maffucci's syndrome, a congenital condition of generalized mesodermal dysplasia, is most often associated with multiple enchondromas and soft tissue hemangiomas or lymphangiomas. This case report describes the development of an unusual ovarian fibrosarcoma and subsequent ovarian adenofibroma in a young woman with the syndrome. The importance of aggressive surveillance in this and similar orthopedic syndromes is stressed.

Risk factors for breast fibroadenoma in young women.

In a case-control study, 178 women diagnosed with fibroadenoma (FA) between 1976 and 1982 were compared with 178 age-matched controls in order to assess the risk factors for FA. Women who had a previous diagnosis of breast disease were excluded. The odds ratios (OR) of FA were calculated for different risk factors of breast disease from bivariate analysis as well as multivariate regression analysis. The highest ORs were found for a previous premenstrual mastalgia before first childbirth and a familial history (FH) of breast cancer (BC). Oral contraceptive (OC) use before a first full-term pregnancy (FFTP) does not modify this risk. Also current use of standard oral contraceptives (SOC) containing 50 micrograms of ethinyl estradiol per pill appeared to be protective and the correlation with FA was negative. These findings underline: (a) the predictive value of premenstrual mastalgia for the subsequent development of breast disease; (b) only current high-dose OC use is protective.

Dose-rate effects of mammary tumor development in female Sprague-Dawley rats exposed to X and gamma radiation.

Mammary tumour development was followed in two experiments involving a total of 2229 female Sprague-Dawley rats exposed to various doses of X or gamma rays at different dose rates. The data for another 462 rats exposed to tritiated water in one of these experiments were also analyzed. The incidence of adenocarcinomas and fibroadenomas at a given time after exposure increased linearly in proportion to total radiation dose for most groups. However, no significant increase in adenocarcinomas was observed with chronic gamma exposures up to 1.1 Gy, and the increase in fibroadenomas observed with chronic gamma exposures at a dose rate of 0.0076 Gy h-1 up to an accumulated dose of 3.3 Gy was small compared to that observed after acute exposures. The incidence of all mammary tumors increased almost linearly with the log of dose rate in the range 0.0076 to 26.3 Gy h-1 for 3 Gy total dose of gamma rays. The effects of X rays appeared to be less influenced by dose rate than were the effects of gamma rays.

A prospective study of the development of breast cancer in 16,692 women with benign breast disease.

The authors studied the relation between benign breast disease and subsequent breast cancer in 16,692 women with biopsy-diagnosed benign breast disease who had participated in the Breast Cancer Detection Demonstration Project throughout the United States. Women were classified into one of five benign breast disease categories: atypical hyperplasia, proliferative disease without atypia, nonproliferative disease, fibroadenoma, and other benign breast disease. A total of 485 incident cases of breast cancer were identified in the women from August 1973 to February 1986 after a median follow-up period of 8.3 years from the diagnosis of benign breast disease. Age-adjusted incidence rates were calculated for benign breast disease types stratified by family history and calcification status. Relative risk (RR) estimates of breast cancer for women in the five benign breast disease categories, compared with the screened women who did not develop recognizable breast disease (normal subjects), were computed using the proportional hazards model. Results indicated that risk was associated with the degree of epithelial atypia. Over all age groups, women with nonproliferative disease, proliferative disease without atypia, and atypical hyperplasia displayed progressively increasing risks of 1.5, 1.9, and 3.0, respectively, compared with normal subjects, with 95% confidence intervals (CI) exceeding unity. Particularly high risk was seen among women under age 46 years with atypical hyperplasia (RR = 5.7, 95% CI 3.0-10.6). Women with fibroadenoma as the only indication of their benign breast disease had a relative risk of 1.7, with a lower 95% confidence limit of 1.0. No increased risk was seen for women with other benign breast disease. Positive family history (RR = 1.8) and calcification (RR = 1.2) significantly increased a woman's risk proportionately over the risk associated with each benign breast disease subtype. The authors conclude that the risk of developing breast cancer varies by category of benign breast disease and is directly related to the degree of epithelial atypia.

The relationship between dietary fat, adipose tissue composition, and neoplasms of the breast.

Dietary fat has been implicated in the development of carcinoma of the breast. Because of the difficulties in obtaining accurate dietary histories, we analyzed subcutaneous adipose fatty acids to compare the quality of fat intake in three groups of patients undergoing investigations for breast masses. These included carcinoma (n = 37, avg. age 54 yrs.), fibroadenoma (n = 27, age 31 yrs.), and other types (n = 21, age 50 yrs.). Subjects in the carcinoma group were heavier, although they were not obese. A one-way analysis of variance of nine adipose fatty acids and their derived ratios [polysaturates:saturates (P:S)] did not show any systematic differences in the three groups. The quality of dietary fat does not appear to be associated with the development of neoplasia of the breast in this population, which consumes a diet of a high P:S ratio.

Assessment of interaction among three carcinogens on rat mammary carcinogenesis in a factorially designed experiment.

Female Sprague-Dawley rats were given by stomach tube 7,12-dimethylbenz[a]anthracene [(DMBA) CAS: 57-97-6] on the 77th day of age at the rate of 1.6 mg/100 g body weight, or procarbazine [(PCZ) CAS: 671-16-9] on the 84th day of age at the rate of 10 mg/100 g body weight, or 0.5 Gy of total-body x-rays on the 91st day of age, singly or in all possible combinations or no treatment. All rats were studied for mammary carcinogenesis for 370 days after the 84th day of age. Three measures of mammary carcinogenesis were studied. These were the incidence of rats with mammary adenocarcinomas, or mammary fibroadenomas, or mammary neoplasia of either type. Each of these measures was studied also for rats with 2 or more or 3 or more mammary neoplasms. Assessment of possible interaction among the three carcinogens with regard to the incidence of neoplasms was done by time-independent or time-dependent methods, both of which gave remarkably consistent results. For rats with 1 or more adenocarcinomas, 1 or more fibroadenomas, or 1 or more adenocarcinomas and/or fibroadenomas, both methods showed no interaction among the carcinogens, which can, therefore, be considered to have produced additive effects. An exception to this finding of additivity was an apparent synergistic interaction between DMBA and PCZ when the measures of rats with 2 or more, or 3 or more mammary neoplasms of either type, or 3 or more fibroadenomas were analyzed; these analyses, however, were based on relatively small numbers of rats with multiple tumors. Since no interactions were found for the usual measure of carcinogenesis, namely, incidence of rats with 1 or more neoplasms, the overall conclusion is that DMBA, PCZ, and x-ray act additively in the induction of mammary neoplasms in the female Sprague-Dawley rat.

Effect of moderate vitamin A supplementation and lack of dietary vitamin A on the development of mammary tumors in female rats treated with low carcinogenic dose levels of 7,12-dimethylbenz(a)anthracene.

We examined the effect of moderately increased and of marginal continued dietary supplementation of vitamin A (retinyl acetate) and the effect of lack of dietary vitamin A on the initiation and promotion stages of mammary tumorigenesis in female Sprague-Dawley rats treated with a single low (0.5 mg/100 g body weight) or very low (0.1 mg/100 g body weight) dose of i.v.-administered 7,12-dimethylbenz(a)anthracene. The number of mammary tumors was significantly (P less than 0.05) reduced if prior to and during initiation with 7,12-dimethylbenz(a)anthracene the rats were fed a moderately increased (30 micrograms/day) or marginal (3 micrograms/day) amount of vitamin A, compared to rats fed an adequate (10 micrograms/day) amount of vitamin A. The number of mammary tumors was also significantly (P less than 0.05) reduced when a moderately increased or marginal amount of vitamin A was provided during the tumor promotion phase. In addition, the number of mammary tumors was significantly (P less than 0.05) reduced by the lack of dietary vitamin A during both the initiation and promotion stages of this tumorigenic process, when compared to vitamin A adequate, ad libitum-fed rats, but not when compared to vitamin A adequate, food-restricted controls. The reduction in numbers of mammary tumors observed in these studies was reflected primarily in significant (P less than 0.05) decreases in mammary fibroadenomas; the number of mammary carcinomas was often reduced, but due to a low frequency of the carcinomatous lesions, this reduction did not reach the 5% level of statistical probability. Plasma and liver vitamin A levels were determined during both the initiation and promotion stages. As the dietary supplementation of vitamin A increased from 0 to 30 micrograms/day, there was an increase in mean liver and plasma vitamin A levels. No consistent correlation between plasma and liver vitamin A levels and the occurrence of mammary tumors was observed, except with the moderately increased (30 micrograms/day) intake of vitamin A, that resulted in a small, but statistically significant (P less than 0.05) increase of serum retinol at initiation; this may account for the observed reduction in mammary tumors. These results provide evidence that moderate alterations in vitamin A consumption can modulate low-dose chemically induced mammary gland tumorigenesis. Most importantly, suppression of mammary gland tumorigenesis can be achieved by moderately increased, frequent, and regular consumption of vitamin A; prolonged consumption of vitamin A-deficient diets or diets marginal in vitamin A does not enhance the risk of mammary tumor development.

Malignant endometrioid adenofibroma of the ovary with serous cystadenoma.

This is a case report of malignant endometrioid adenofibroma of the ovary with serous cystadenoma in a 42-year-old female. It was classified as FIGO serous IA (2) ovarian tumors. Serous epithelium transformation into endometrioid glandular epithelium was disclosed. The patient is now in good condition and followed-up periodically.

Actuarial analysis of the hazard for mammary carcinogenesis in different rat strains after X- and neutron irradiation.

Mammary carcinogenesis in three different rat strains has been studied after single and fractionated irradiations with X-rays and monoenergetic neutrons of three energies. The aims of the programme are the investigation of the nature of the dose-effect relationships, and the determination of the relative biological effectiveness (RBE) of neutrons. Histopathological examinations of tumours has been completed and dose-effect relations are reported separately for the induction of benign and malignant lesions. Appropriate corrections have been made for competing risks in the tumour rate analysis. The probability curves for survival without evidence of tumours have been described by Weibull distributions. This continuous parametric failure-time model is used to derive the relative excess hazard for exposure to X-rays and neutrons. The different rat strains show considerable differences in susceptibility for the induction of cancer by radiation. In general linear dose-response curves have been observed for mammary tumourigenesis in the three rat strains for both X-rays and fast neutrons. Within the statistical precision of the data a dependence of the RBE on neutron dose cannot be recognised. The highest RBE values, varying between 7 and 15 for different types of tumours in the three rat strains have been observed for 0.5 MeV neutrons. These RBE values are lower in general than those observed by other groups for beams of comparable energy.