Results of treatment of breast cancer with tamoxifen]

There were 62 cases of mammary carcinoma treated with the antioestrogen tamoxifen. The age of the patients ranged from 35 to 75 years. Tamoxifen was administered in a daily dosage of 30 mg (3 x 1 tablet). Treatment was carried out as monotherapy or adjuvant therapy. Treatment was carried out for 6 months with a follow-up period of further 6 months. In the group of patients with mammary carcinoma, 23 were premenopausal without metastases after radical mastectomy and sterilisation. The remaining 39 in this group were in the menopause with metastases which were in some cases untreated and in some cases treated by mastectomy, radiation and chemotherapy (CMF-scheme). All Patients were PD in relation to further radiation and/or chemotherapy. Karnofsky-index was 60 minimum. After 4 weeks' treatment with tamoxifen both an improvement in general wellbeing and a regression of the focus of the tumour was achieved. A significant improvement in wellbeing and tumour status could be established for a total of 48 cases of mammary carcinoma. Treatment was well tolerated. Only 1 case of side effects in the form of vomiting occurred.     

Morphologic features and incidence of spontaneous hyperplastic and neoplastic mammary gland lesions in Wistar rats

A morphologic study of spontaneous proliferative lesions of the mammary gland was based on histologic examination of mammary glands from 1020 male and 1145 female albino Wistar rats aged 6 to 110 weeks. Three hundred and seventy-five mammary tumors representing an overall incidence of 33% were identified in the female groups, while the males had a total of five tumors which represented an incidence of 0.5%. Histologically, the most common types of tumors in females were: fibroadenoma (236), carcinoma (85), adenoma (40) and fibroma (8). Duct papilloma (1), lobular carcinoma (1), fibrosarcoma (1) and phyllodes tumor (1), were rare and constituted less than 2% of mammary neoplastic lesions. Mammary tumors were rare before one year of age, but increased with age thereafter. Nine percent of female rats studied also had proliferative non-neoplastic lesions that showed a mixture of benign ductular and/or lobular hyperplasia. One hundred and six of these lesions were identified, representing 22% of all grossly palpable nodules, thus stressing the importance of histologic examination of all gross mammary nodules for tumor evaluation.     

Detection of Inoue-Melnick virus (IMV)-antibody in Japanese patients with colorectal carcinoma and isolation of IMV from Japanese colorectal carcinoma cell lines

The antibody prevalence rate of 3 types of IMV in 24 sera of Japanese patients with colorectal adenocarcinoma (mean age 60.8 years) was 83.3% (20/24). Of 20 positive sera, 19 contained type 1 antibody and one contained type 2. In contrast, the seropositivity of IMV in 21 sera of matched control patients (mean age 60.9 years) with non-colorectal carcinoma such as mammary and lung carcinoma was 23.8% (5/21). The 5 positive sera contained type 1 antibody. The seropositivity to IMV in 79 sera of healthy Japanese over 50 years of age (mean age 62.3 years) was 24.0% (19/79). Again all of the 19 positive-sera contained type 1 antibody. The seropositivity of IMV in the patients with colorectal adenocarcinoma was significantly higher than in the controls, non-colorectal carcinoma patients and healthy persons over 50 years of age (P less than 0.001). Type 1 IMV was isolated from each of 2 recently established Japanese colorectal adenocarcinoma cell lines.     

早期食管原发性腺癌初步病理分析

通过7例早期食管原发性腺癌手术标本系列大切片的观察,证明在早期食管癌中确有原发性腺癌存在。患者平均年龄46岁,较中晚期癌患者年轻约10岁。病理类型以浅表缺损型为主,癌灶平均长度13mm。病理特征为:(1)癌变多起始于食管固有腺腺管上段,可在相邻数个腺体内同时发生;(2)组织学上多表现为腺管癌;(3)癌灶表面和周围覆盖有受压变薄或呈增生性改变的鳞状上皮;(4)多伴有鳞癌成分。     

Enhancement of mechanisms acting against mammary carcinoma: Pancreatic trypsin inhibitor

Summary Human mammary carcinoma cells were cultivated from primary tumor explants in Eagle's minimum essential medium (MEM) supplemented with Insulin-Penicillin-Streptomycin-Fetal Calf Serum (35–45%) and/or pancreatic trypsin inhibitor. In MEM supplemented with Insulin-Penicillin-Streptomycin-Fetal Calf Serum (15%) the mammary carcinoma cells were produced from the primary explants with an abundance of pseudopodia-like fibers extending from the explants connecting and surrounding groups of cells. These cells survived 3 to 5 weeks and died. If the medium was supplemented with pancreatic trypsin inhibitor (10 µg/ml) the mammary carcinoma cells were produced from the explants as separate round bodies which developed into fusiform or triangular cells, without any interlinking or protecting structures. These cells survived from several months to over a year. After several (18 to 48) weeks of cultivation in presence of pancreatic trypsin inhibitor, the human mammary carcinoma cells became more sensitive to the cytotoxic effects of serum from post surgery patients with mammary carcinoma. Some of these cultures responded to the dual effect of high and low doses of oestrogens and to the effect of prolactin. In the presence of insulin, the cultivated cells synthesized alpha lactalbumin a characteristic of mammary tissue.     

Periacinar retraction clefting in proliferative prostatic atrophy and prostatic adenocarcinoma

AIMS: To evaluate the presence and extent of periacinar retraction clefting in proliferative prostatic atrophy and carcinoma in radical prostatectomy specimens. METHODS: Atrophic foci and neoplastic glands were analysed in specimens from 50 patients who underwent radical prostatectomy. Analysed atrophic glands were classified in two main groups, proliferative atrophy (PA) and proliferative inflammatory atrophy (PIA); each group was subclassified into simple atrophy (SA) and postatrophic hyperplasia (PAH). According to the presence and extent of periacinar retraction clefting, atrophic and neoplastic glands were classified as: group 1, glands without clefts or with clefts affecting 50% of the circumference in <50% of examined glands; and group 3, glands with clefts that affected >50% of the circumference in >or=50% of examined glands. RESULTS: Forty-four (88.0%) atrophic foci were without periacinar clefts or clefts were present in less than half of the gland circumference (group 1). In 6 (12.0%), atrophic foci clefts affected >50% of gland circumference (groups 2 and 3). Forty-five (90.0%) carcinomas were with clefts which affected more than 50% of gland circumference (groups 2 and 3); and in five carcinomas only, clefts were not found or affected <50% of gland circumference (group 1). CONCLUSION: Results indicate that periacinar retraction clefting represents a reliable criterion in differential diagnosis between proliferative atrophy and carcinoma.     

Pathogenetic mechanisms of cyst formation in the breasts and mammae]

Mammary glands and endocrine organs of human females ranging in ages from 6 months to 25 years (228 cases) as well as in intact, castrated, hypophysectomized, thyroidectomized, adrenalectomized young virgin female rats treated with steroid hormones and thyroxin were studied by various morphological methods. The process of cyst formation in female mammary glands was found to be enhanced by intensified endocrine influences on them in the interval of 6 months to 2 1/2 years (the effect of maternal hormones received by the baby with milk) and from 11 to 15 years (physiological activation of endocrine glands) and to decline in the period of relative quiescence at the age of 2 1/2 to 11 years. Both hyperestrogenism and hypercorticism and hypofunction of the thyroid gland as well as dysfunction of adenohypophysis and neuro-trophic apparatus of mammary glands are important in the pathogenesis of cysts.     

Age at menopause and prevalence of its different types in contemporary Greek women

OBJECTIVE: This study attempted to estimate the mean age at menopause and also characterize and quantify its types and frequencies in Greek women who have recently become postmenopausal. DESIGN: A retrospective analysis of hospital records was used to record the frequency of natural, spontaneous or induced premature, and delayed natural menopause; the mean age at menopause of each group; and their possible interrelationships with major events of reproductive history in 1,747 women visiting an endocrine clinic 1 to 5 years after menopause. A group of 438 postmenopausal women drawn from 4,000 cases from the nongynecological clinics of this hospital comprised the control group. RESULTS: Natural menopause was found in 1,333 (76.3%) women with a median age of 51 (95% CI, 50.8-51.2) and mean +/- SD of 48.7 +/- 3.8 years. Medically induced menopause after the age of 40 was recorded in 204 women (11.7%), spontaneous premature in 127 (7.1%), medically induced premature in 60 (3.7%), and delayed menopause in 26 (1.5%), with mean ages of 43.6 +/- 1.7, 35.1 +/- 3.3, 37.2 +/- 1.6, and 59.6 +/- 2.1 years, respectively. No significant differences in mean age at menopause or its types were noted between the two groups. Furthermore, no significant correlations among the parameters examined could be demonstrated except between smoking and age at menopause in the spontaneous premature menopause subgroup (P < 0.05). Finally, ovarian autoantibodies were found in 6.7% of the tested women with premature menopause. CONCLUSIONS: Natural menopause occurred at a mean age of 48.7 years in Greek women, who displayed an unexpectedly high prevalence of spontaneous or induced premature cessation of menstruation.     

The age at menopause and associated factors at the health center area in Ankara, Turkey

OBJECTIVES: This study is performed in one health center area in Ankara, Turkey on a women population of 50-65 years in order to demonstrate menopausal status of women, age at menopause and factors related with the age at menopause. METHODS: This is a cross-sectional study which has been performed on a women population of 50-65 years. The local population was 17,153 in this area by 2001. All of the household determining forms are screened in order to detect the all of the women who were in 50-65 years group, then name and addresses of the these women's are listed. There were 1089 women aged 50-65 years who were constituting 7% of the population. After choosing the first name randomly from the list of the women, 1/3 systematic sampling method was used and, the number of the women in the sampling was 363 (95% C.I., +/-5% S.E.). The response rate among those eligible women who were contactable during the study was 99% (360/363). Data were collected by interviews through questionnaires. The questionnaire consisted of a series of questions concerning age at menopause, socioeconomic status, age at menarche, age at first pregnancy, regularity of menstrual cycles, parity, duration of breast feeding, use of OCs, BMI, smoking habit, age at menopause of the mother and the sister. Chi-square and t-test methods were used for statistical analyses. RESULTS: 4.2% of the women were in premenopause, 13.3% were in perimenopause, 72.8% were in natural menopause and 9.7% were in surgical menopause. Average age at natural menopause was 47+/-4.2 years. Education, age at menarche, smoking, age at menopause of the mother and the sister were found to be related with the age at menopause. CONCLUSIONS: Ninety-six percent of the women over age of 50 years, are at menopause or perimenopause. The results of this study suggest that, for factors of genetic and age at menarche, there are not many possibilities for the lifestyle changes that would modify age at menopause with the subsequent reduction in risk for chronic diseases, but daughters or sisters of women with an early menopause and women who smoked or less educated could be counselled with respect to family timing.     

The idiopathic forms of premature menopause and early menopause show the same genetic pattern.

Genetic factors may influence the timing of menopause. Premature ovarian failure (POF) has recently been identified as a genetic entity, but no genetic data are available on early menopause (EM). We investigated 36 patients with EM (age of menopause between 40 and 45 years of age) using cytogenetic and pedigree analysis. In 30 patients of this study the EM was idiopathic and 15 subjects (50%) had a familial condition of EM or POF. Pedigree analysis revealed a dominant pattern of inheritance of EM through maternal or paternal relatives. Our data reveal that POF and EM patients show the same genetic features and we postulate that these conditions may be a variable expression of the same genetic disease.     

Age and symptom experience at menopause in the Selska Valley, Slovenia

OBJECTIVE: To assess age and symptom experience at menopause in a high-altitude population in the Selska Valley of Slovenia. DESIGN: In four mountain villages, all houses were approached and 80% of eligible residents were interviewed. Additional women were interviewed for comparison in the valley below. Age at interview ranged from 32.7 to 85.5 years, with a mean of 58.2 years. The majority of women (62%) were aged 40 to 65 years. RESULTS: Of the 58 women interviewed, 7 had undergone menopause by hysterectomy (12%). Recalled age at natural menopause ranged from 42 to 54, with a mean of 50.3 (SD 2.9). By probit analysis, median age at natural menopause was 52.03. Fifty-five percent of participants reported ever having experienced a hot flash, although only 24% reported hot flashes during the 2 weeks before being interviewed. When the sample was limited to women aged 40 to 65, frequency of hot flashes in the 2 weeks before the interview was 39%. For all participants, the most frequent complaint was lack of energy (66%), followed by backaches (59%), and joint stiffness (53%). CONCLUSIONS: In contrast to expectations, age at menopause was not earlier and hot flash frequency was not significantly lower at higher elevations.     

Causes of death of patients with breast cancer (according to the materials of the Oncological Research Center of the USSR AMS for the period 1953-1975)]

The article presents results of investigations of 207 case records and protocols of autopsies of deceased patients who suffered from breast cancer, covering the period from 1953 to 1972 (materials of the USSR AMS Oncological Research Centre). It was established that in 154 patients (74.4%) the cause of death was the progress of the main disease, the most common and "typica" causes of death being pulmonary-cardiac, renal insufficiency (as a result of metastatic lesions of the above mentioned organs) and complications associated with metastases of breast cancer in to the brain and its meninx. In 39 patients (18.8%) the cause of death was directly associated with therapy complications, 14 patients died of diseases not connected with carcinoma of the mammary gland. The structure of causes in the group of deceased patients who when alive suffered from cancer of the mammary gland and who survived 10 and more years from the moment of establishing the diagnosis and carrying out primary treatment (11 observations) was found to be the same as that for the whole group of observations.     

Effects of hyperinsulinemia on lactose secretion and glucose uptake by the goat mammary gland

Hove , K. Effects of hyperinsulinemia on lactose secretion and glucose uptake by the goat mammary gland. Acta physiol. scand. 1978. 104. 422–430. Lactose secretion by goat mammary glands was studied after intra-arterial infusions of insulin and/or glucose causing rises in plasma insulin concentrations in mammary venous blood of about 3–5 mg/ml. Such levels are sufficient to strongly stimulate insulin sensitive processes when present in the systemic circulation. Two goats with mammary glands in situ and two with one of the glands autotransplanted to the neck were used for the experiments. Increasing the insulin concentration in blood to the mammary gland induced a decrease in lactose yields during a 3 h infusion (p < 0.02). Simultaneously arterial plasma glucose decreased by 15–20 mg/100 ml to about 50 mg/100 ml. When the systemic hypoglycemic effect of the insulin infusion was offset by a simultaneous intra-venous infusion of glucose, no significant change in lactose secretion was observed during 8 hours of hyperinsulinemia. No change in mammary glucose uptake as measured by mammary blood flow x mammary arterio-venous glucose differences could be detected. (Average glucose uptake for 2 h before infusion: 30.9 mg/min; during 8 h of infusion: 31.2 mg/min.) It may be concluded that increased levels of insulin in the blood perfusing the mammary gland did not affect mammary glucose uptake or lactose synthesis as long as blood glucose was maintained at normal levels. The results therefore indicate that the glucose turnover in mammary glands, which in high yielding dairy ruminants represents the main organ of glucose utilization in the body, is in fact independant of changes in plasma insulin concentrations.     

Immunohistochemical staining patterns of tenascin in invasive breast carcinomas

Summary Eighty-two cases of primary invasive breast carcinoma and adjacent normal mammary glands were examined immunohistochemically for tenascin expression and distribution. Formalin-fixed tissues pretreated with actinase were processed by the avidin-biotin complex method using anti-human tenascin monoclonal antibody (RBC1). In normal mammary glands, tenascin was distributed around the ducts and ductules but not around the acini. In carcinomas, a high incidence of tenascin-positive cases (>67%) was seen with various histological appearances, with the exception of lobular carcinoma where a low incidence was found (25%). Although intense staining was seen around cancerous foci when compared with normal mammary glands, tenascin was often expressed at cancer-mesenchymal junctions with dense fibrotic stroma, but not at junctions with active inflammatory change and a loose fibrotic stroma. Tenascin expression is not an all-or-none marker for mammary malignancy and the staining pattern suggests either a role in stimulating cancer cells or a host defence mechanism accompanied by a desmoplastic response to them.     

Cross-sectional and case-controlled analyses of the association between smoking and early menopause

To examine potential confounders and dose-response data for the association between smoking and menopause, we used both a cross-sectional and case-controlled approach. In total, 10 606 middle-aged women residing in eastern Massachusetts were surveyed about their age at menopause and smoking history; 344 women (cases) with natural menopause prior to age 47 and 344 age-matched women (controls) who were still menstruating or who had a menopause after age 46 were selected for further study. Risk for menopause was assessed by Kaplan-Meier, Cox proportional hazards, or logistic regression models. From cross-sectional data on 8657 women aged 45–54, the hazards odds ratio for a natural menopause among women who ever smoked compared to non-smokers was 1.31 (95% C.L. 1.21–1.42) and among women who had accumulated 30 or more pack-years was 1.87 (95% C.L. 1.67–2.04) after adjustment for parity and weight. An additional potential confounder from the case-controlled study was lower educational attainment, and after adjustment for this variable, significant trends persisted for risk of early menopause associated with age began smoking (P = 0.03), years of smoking (P = 0.01) and pack-years of smoking (P = 0.03). This study demonstrates an association between smoking and early menopause in both cross-sectional and case-controlled data that is not confounded by parity, weight, socio-economic status, or nutritional variables.     

Age at natural menopause and cognition

OBJECTIVES: To examine associations between age at natural menopause, childhood IQ and cognition at age 65 years. To determine if lower age at menopause partly mediates the effect of childhood IQ on cognition at age 65 years. METHODS: Data were provided by a sub-cohort of women participating in a longitudinal study of brain ageing and health. Main variables were childhood IQ from a 1947 national survey of children born in 1936, age at natural menopause and five cognitive tests measured in 2000-2001. RESULTS: Age at menopause was associated with childhood IQ (r = 0.221, P = 0.008) and with general cognitive function age 65 years (r = 0.246, P = 0.004). Multiple regression showed 44.4% of the reliable variance in cognitive ability age 65 years is contributed by IQ at an age of 11 years to which, years of education contributed an additional 3.9%. Structural equation modelling suggested that childhood IQ differences contribute 4.8% of the variance to age at natural menopause and that the relation between age at menopause and cognition at age 65 years was accounted for by childhood IQ. CONCLUSION: Childhood IQ and age at menopause each have significant relations with general cognitive function age 65 years but the link between cognition age 65 years and age at menopause might be wholly explained by childhood IQ. The association between childhood IQ and age at menopause may be attributed to central neural mechanisms or, as argued here, to the effects of childhood IQ on adult general health.     

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease.

Mammary Paget's disease and extramammary Paget's disease are rare intraepithelial neoplasms. Mammary Paget's disease is almost exclusively associated with underlying invasive breast carcinoma or high-grade ductal carcinoma in situ (DCIS G3). Extramammary Paget's disease arises in areas rich in apocrine glands and is suspected to have apocrine gland origin. The aim of the study was to investigate the presence of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and Her2/neu in a large number of cases. We investigated 58 cases of mammary and 23 cases of extramammary Paget's disease. Formalin-fixed and paraffin-embedded tissues were analyzed using antibodies against AR, PR, ER and Her2/neu according to standardized procedures. In mammary Paget's disease, positive immunoreactions for Her2/neu, AR and ER were observed in 56 of 58 (97%), 51 of 58 (88%), and respectively in six of 58 (10%) cases. All cases of mammary Paget's disease were negative for PR and showed a coexpression of Her2/neu and AR in 51 out of 58 cases (88%). In extramammary Paget's disease, positive immunoreactions for AR, Her2/neu and ER were observed in 18 of 23 (78%), 12 of 23 (52%), and respectively in 1 of 23 (4%) cases. All cases of extramammary Paget's disease were negative for PR and showed a coexpression of AR and Her2/neu in 12 out of 23 cases (52%). In contrast to ER and PR, AR and Her2/neu are commonly expressed in mammary and extramammary Paget's disease. The knowledge about frequent expression of AR in Paget's disease could lead to the development of a new adjuvant therapy, particularly in patients with recurrent disease.     

Correlates of the age at natural menopause in Morocco

Primary objective : To determine the median age of natural menopause and factors associated with the timing of menopause in Morocco. Research design : A population-based sample of 299 women from Rabat, Morocco were interviewed using a semi-structured questionnaire. Methods and procedures : Logit analysis and logistic regression were used to estimate the median age and identify factors associated with the age at menopause. Main outcomes and results : The median age of natural menopause in Morocco is estimated to be 48.4 years (95% CI: 36.9, 70.3). Women who reported the onset of menstruation at age 11 or younger (OR = 2.84, 95% CI: 1.00, 8.10) had an earlier age at menopause than women who started menstruating at age 12 or older. Women who had ever used oral contraceptives were more likely to have a later age at menopause (OR = 0.55, 95% CI: 0.30, 1.00). The length of time a woman used oral contraceptives influenced the timing of the menopause in unadjusted models but after adjusting for the age at menarche the effect was no longer statistically significant. Marital status, parity, education level, and social class were not statistically associated with the age at menopause. Conclusions : The estimated age at natural menopause in Morocco is 1-3 years earlier than the median ages reported in industrialized countries and some developing countries. Factors that alter the frequency of ovulation or rate of follicular atresia appear to be important in determining the age at menopause.     

Squamous carcinoma of the lip. Review of 98 cases

Squamous lip carcinoma. A review of 98 cases. Ninety-eight new cases of squamous lip carcinoma (87 males and 11 females), diagnosed over a 10 year period at the Institute of Pathological Anatomy of the University of Trieste were studied from an epidemiological point of view and in relation to their biological behaviour. The overall incidence was equal to 6.67%... in males and 0.73%... in females, with a male to female ratio of 9.2:1. The distribution of the cases can be directly correlated to age: the incidence in the 80-84 age group among males was 3 times greater than that in the 60-64 age group and 4 times greater than that in the 55-59 age group. Among females the highest number of cases occurred from 85 years of age upwards. The relative frequency of the carcinoma for each of the 3 epithelial surfaces was 46.9% for skin lesions (46 cases) and 50% (49 cases) for those on the vermilion, while the carcinoma originated in the internal mucosa in just 3 cases. In 11 cases the tumour had originated on the upper lip (8 males and 3 females, male to female ratio 2.6:1) and 6 of these were skin tumours. The relative frequency of skin neoplasms of the lip was 38.8% for 1978-81, 43.3% for 1982-85 and 64% for 1986-87. A study of the age specific incidence showed that the maximum number of cases occurred in the 75-84 age group (8.37%) for vermilion carcinomas and in patients over 85 (7.69%) for skin of lip carcinomas. In 17 patients the tumour was already infiltrating at the first biopsy (13% of skin carcinoma and 23% of carcinomas arising on the mucosa), and in 9 cases there were metastasis to the laterocervical nodes and/or salivary glands. In 14 patients the tumour recurred. From a study of the autopsies on the 27 patients who died it emerged that in 18 cases (66.6%) there was no tumour, nor was there any local infiltration or metastasis, while in 4 cases the tumour was still present and infiltrating the surrounding tissue. In 4 other cases the primary tumour was no longer present but metastasis and/or infiltration had developed. Associations with one or more malignant neoplasms of the oral cavity or the upper aerodigestive tract were noted in 9 cases.     

Are the effects of risk factors for timing of menopause modified by age? Results from a British birth cohort study

OBJECTIVES: This study investigated the influence of mother's age at menopause, early life and adult behavioral factors on the timing of menopause until age 57 years, and whether these effects vary according to the women's age at menopause. DESIGN: A nationally representative cohort of 1,583 British women born in March 1946 with prospective data across the life course. For factors that vary with age at menopause, analyses were stratified by age at menopause younger than 50 years or 50 years or older. RESULTS: Cox regression models indicated that for women with earlier menopause, those who were heaviest at 2 years had a 59% lower hazard ratio for menopause than those who were the lightest (hazard ratio [HR]=0.41, 95% CI: 0.16-1.01), whereas this figure was 35% lower (HR=0.65; 95% CI: 0.42-1.00) for the later menopause group. For women in the earlier group with parental divorce during childhood, the HR was 6.5 (95% CI: 2.021.3) times higher than that of other women. This rate decreased to 2.5 (95% CI: 1.5-4.2) for those with later menopause. In both groups, increasing mother's age at menopause was associated with decreasing HR (P<0.0001). For all women, being breast-fed (P=0.05), increasing cognitive ability (P=0.009), and increasing parity (P=0.001) delayed menopause. CONCLUSIONS: This study found that the impact of weight at 2 years, parental divorce during childhood, and mother's age at menopause varied according to the women's age at menopause. There was further evidence that being breast-fed, higher childhood cognitive ability, and increasing parity delayed menopause. These results suggest the interaction of genetic and environmental factors in determining age at menopause.