Distribution of 17 beta-estradiol in the sera of normal British and Japanese women.

Normal Japanese women had significantly more of their blood 17 beta-estradiol (E2) bound to sex hormone-binding globulin (SHBG) (53%) than British women (30%) and conversely less bound to albumin. While the proportion of SHBG-bound E2 increased with SHBG capacity and while binding fell as weight increased, the differences between the races do not appear to be explicable in terms of SHBG capacity or weight. At a given SHBG capacity, the Japanese women had more E2 bound to the protein than the British women. Where weights in the 2 populations overlapped, the Japanese women still had more of their E2 bound to SHBG than did the British women. Our results suggested that the affinity of albumin for E2 is lower in Japanese women.

Thymus and breast cancer--plasma androgens, thymic pathology, and peripheral lymphocytes in myasthenia gravis.

Plasma androgen sulfates were measured in 92 patients with myasthenia gravis. Plasma androgen sulfates were strongly associated with thymic pathology. The presence of germinal centers was associated with decreased androgen levels. A weak but significant positive correlation existed between androgen sulfates and lymphocyte counts. Low lymphocyte counts in patients with germinal centers were associated with subnormal androgen concentrations. Plasma androgen sulfate levels decreased immediately after thymectomy, but overall no significant differences were found between prethymectomy and post thymectomy levels. A trend toward higher concentrations of plasma androgens was noted 5 or more years post thymectomy. Plasma androgen sulfate levels in myasthenia gravis patients with breast cancer were markedly depressed. The lowest androgen sulfate levels were observed in patients who had previous bilateral breast cancer and those who, subsequent to the determination of the steroid sulfates, developed a second primary lesion of the breast.

Steroid hormones in lymph and blood from women with early breast cancer.

Postoperative levels of steroid hormones have been measured in lymph and blood of 28 patients undergoing iridium implants as part of conservative treatment for operable breast cancer. The aim was to establish whether there were higher levels of hormones in lymph draining from necrosing tumour cells compared with peripheral blood levels. No differences were found in the ratios of estradiol, dehydroxyepiandrosterone sulphate or sex hormone-binding globulin in those patients with complete compared with incomplete excision of the primary tumour. However, premenopausal patients who had an incompletely excised primary tumour had increased levels of free testosterone in lymph draining from the tumour site on the third and fourth postoperative days. Thus androgens may have an important role in the intracellular metabolism of some breast cancers.

Selenium in human mammary carcinogenesis: a case-cohort study.

In a prospective study conducted on the island of Guernsey a cohort of 5162 ostensibly healthy women was enrolled between 1967 and 1976. Blood samples were drawn from each participant, who also completed a questionnaire, which provided information on established risk indicators in human mammary carcinogenesis. Plasma selenium levels were measured in 46 breast cancer cases diagnosed a mean of 11 (S.D. 4) years after entry into the study cohort and in an age-stratified sample of 138 women drawn from the study base. Plasma selenium level in the cases was 109 (28) micrograms/l and in the base sample 103 (22) micrograms/l (95% confidence interval for the overall difference, -2 to 14 micrograms/l). The adjusted relative risk of developing breast cancer in the different quartiles of the selenium distribution was 0.80, 0.79, 0.72 and 1.00, respectively. Thus, in the present study selenium was not a strong indicator of human breast cancer risk.

Serum prolactin levels and their relationship to survival in women with operable breast cancer.

The prognostic value of serum prolactin levels was assessed in a sequential series of 739 patients who were initially treated at Guy's Hospital, London, between 1975 and 1980. Prolactin was measured in 472 patients 1 day before (Hpr1) and in 457 patients 10 days after (Hpr2) mastectomy. Follow-up of the patients was up to August 1992 giving 6139 women-years with a median follow-up time of 11.5 years (13.7 for patients still living and 5.1 for those dead). The association between the three prolactin variables and reproductive and clinical factors was examined before assessing the prognostic value of prolactin levels in terms of overall, disease-specific and disease-free survival. Multivariate survival models were used in order to adjust for the effect of other prognostic variables. These were found to be: tumour size, degree of nodal involvement, tumour grade and age at diagnosis. The results showed that high Hpr2 or high postoperative increase in prolactin (i.e. Hpr2-Hpr1) were significantly related to shorter disease-specific survival (p = 0.04 and 0.01, respectively) in postmenopausal women. In addition there was some indication, which did not attain formal significance, for this association to occur for disease-free survival. Thus the rise in blood prolactin levels after surgery may be a weak indicator of poor prognosis of breast cancer in postmenopausal women.

Relationship of blood prolactin levels and the risk of subsequent breast cancer.

Between 1968 and 1976 a total of 5162 women volunteers were enrolled into a prospective study conducted on the Island of Guernsey. Up to February 1990 145 women subsequently developed breast cancer. Blood samples were taken at the time of enrollment and prolactin levels were known for 85% of the volunteers. In calculating the relationship between blood prolactin levels and subsequent breast cancer risk, women were excluded if they had a hysterectomy or an oophorectomy or had cancer at any site before enrollment. The final analysis was based on 2596 premenopausal and 1180 naturally postmenopausal women and, of these respectively, there were 71 and 40 volunteers who subsequently developed breast cancer. The total follow-up for these two groups was 49,941 and 22,360 woman-years, respectively. In assessing the relationship between blood prolactin levels and risk of subsequent breast cancer the cohort was divided into quintiles according to prolactin concentration and relative risks (RR) were estimated. In calculating these values possible confounding by age at entry, age at menarche, parity, age at first birth, years since menopause, body build, history of benign breast disease and family history of breast cancer were taken into consideration. There was no significant relation between risk of breast cancer and prolactin in either pre- or postmenopausal women. Hence prolactin appears not to be an important determinant of breast cancer risk.

Relationship of mammographic parenchymal patterns with breast cancer risk factors and risk of breast cancer in a prospective study.

A prospective study has been conducted on 4954 female volunteers from the Island of Guernsey between 1977 and 1985 to examine risk factors for breast cancer and their relationship to mammographic parenchymal patterns as assessed by Wolfe's method of grading. Up to September 1988, 69 women had developed breast cancer, 11 of whom were prevalent cases being diagnosed within six months of mammography. The remaining incident cases were diagnosed six to 126 months (median 65 months) after entry to the study. Univariate analysis showed that the distribution of Wolfe grades in the population was significantly associated with menopausal status, age, parity, adiposity, age at menarche, age at first childbirth and use of oral contraception, but not with a family history of breast cancer. Multivariate analysis of the data for these variables from either pre- and/or post-menopausal women indicated that age, parity and adiposity were significantly related to Wolfe grade pattern. Age had an opposite effect in pre- compared with postmenopausal women thus the probability of either a P2 or DY pattern increased with increasing age in premenopausal but decreased in postmenopausal women so that incidence peaked around the menopause. Other variables did not achieve significance in the multivariate analysis. Odds ratios (ORs) were calculated for women with P2 or DY patterns using those with N1 or P1 grades as the reference group. The ORs were determined at two censoring times; one at five years and the other to include the most recent follow-up of this cohort. The ORs were adjusted for years of follow-up, age and adiposity and in postmenopausal women adjustment was also made for age at menarche.(ABSTRACT TRUNCATED AT 250 WORDS)

Cigarette smoking and steroid hormones in women.

Epidemiological evidence has suggested that cigarette smoking has an anti-oestrogenic effect in women, but the effects of smoking on steroid hormone metabolism are not fully understood. We compared serum concentrations of oestradiol, progesterone (luteal phase) and dehydroepiandrosterone sulphate (DHEA-S), and urinary excretion rates of six steroids of predominantly adrenal origin, in healthy premenopausal and postmenopausal female smokers and non-smokers. Serum concentrations of oestradiol, progesterone and DHEA-S did not differ between smokers and non-smokers by greater than 5%, and none of these differences was statistically significant. Mean urinary excretion rates of androsterone, aetiocholanolone, DHEA, 11-keto-aetiocholanolone, 11-hydroxyandrosterone and 11-hydroxyaetiocholanolone were very similar in smokers and non-smokers in premenopausal women, but were from 2-44% higher in smokers than non-smokers in postmenopausal women. The difference was statistically significant only for 11-hydroxyandrosterone. These results confirm previous reports that cigarette smoking does not affect serum oestradiol in premenopausal or postmenopausal women, but provide only weak evidence to support previous findings of increased levels of some adrenal steroids in postmenopausal women smokers. The mechanism for the apparent anti-oestrogenic effect of cigarette smoking remains unclear.

Sex hormone-binding globulin and the natural history of breast cancer.

Low concentrations of SHBG in the blood appear to be related to rapid tumour growth rates whereas normal values are associated with slower rates. The inferences drawn from these and other experimental results are as follows: 1. It is no longer necessary to postulate that an abnormal endocrine environment is related to the risk of breast cancer. 2. Variation within the normal range of endocrine function may be sufficient to account for marked differences in the growth rates of transformed cells. 3. It is suggested that women whose tumours arise in an environment characterised by SHBG concentrations at the lower end of the normal range (and, hence, non-SHBG-bound oestradiol levels at the top end of the range) will tend to have an earlier age at diagnosis, a lower frequency of oestrogen-receptor positive tumours and a lower proportion of hormone responsive tumours than women with SHBG levels at the top of the range. 4. Case/control studies in which growth rates are not taken into account may be difficult to interpret.

Adjuvant androgen treatment of operable breast cancer--a 20 year analysis.

One hundred and fifty-five patients with carcinoma of the breast treated by mastectomy were randomised to receive no additional treatment or to receive adjuvant testosterone. After a minimum follow up of 15 years there is no difference in either relapse free survival or overall survival between the treated and control groups. Stratification by pathological nodal status showed no benefit either for those with negative or positive axillary lymph node involvement.

The relationships of SHBG with current and previous use of oral contraceptives and oestrogen replacement therapy.

Sex hormone binding globulin (SHBG) concentration was measured in serum samples from 2077 premenopausal and 901 naturally postmenopausal women who had no history of disease or of recent drug use likely to affect SHBG. Current users of oral contraceptives (OCs) and of oestrogen replacement therapy had higher mean SHBG values than non-current users. Both premenopausal and postmenopausal women who had previously used OCs had a lower mean SHBG concentration than never users of OCs. Previous use of oestrogen replacement therapy was not related to SHBG.

The relation between radiological patterns of the breast and body weight and height.

Mammograms were obtained from 942 normal volunteer women aged over 35 years, and were classified by Wolfe's criteria. There was no relationship between height and mammographic pattern. An increase in weight, whether corrected for height or not, was associated with an increase in the proportion of N grades and a concomitant decrease in DY grade mammograms. This effect reached formal significance in pre-menopausal women but was highly significant in post-menopausal women. For women who were either above or below their ideal weight there was a significant positive correlation between parity and the proportion of N and P1 mammograms. The slopes of the linear regression for these two groups were the same, although the elevation of the above-ideal weight group was significantly greater. This implies that for any given parity, there are about 16% more N or P1 grades in the above-ideal compared with the below-ideal weight group.

The relation between radiographic features and determinants of risk of breast cancer.

Mammograms were obtained from 942 normal women aged over 30 years, and were classified by Wolfe's criteria. In women with an enhanced risk of breast cancer associated with a late age at first child or nulliparity, there was a significant increase in the proportion of P2 and DY mammographic patterns which are thought to be a radiological index of risk. There was a decrease in the proportion of P2 and DY grades in women using steroidal contraceptives. However, the association between radiological and epidemiological determinants of risk did not hold for age at menarche.

Breast parenchymal patterns in women with bilateral primary breast cancer.

Mammograms were obtained from 44 women aged over 30 years with bilateral primary breast cancer, 60 women with unilateral breast cancer, matched for age and menopausal status with the bilateral cases, and 937 normal women, again all aged over 30 years. The mammograms were classified according to Wolfe's criteria. Both groups of cancer patients were found to have a significantly (p less than 0.05) greater proportion of pre-menopausal women with the DY type of breast parenchymal pattern compared with the normal pre-menopausal women. No association was found between the P2 mammographic pattern and breast cancer. The study failed to show any difference in the distribution of mammographic risk categories in women with bilateral disease and those with unilateral cancers only.

A prospective study of mammographic parenchymal patterns and risk of breast cancer.

Breast parenchymal patterns have been assessed by the method of Wolfe in a prospective study in Guernsey. Women with P2 or DY grades had approximately four times the risk of developing breast cancer compared with those with N1 or P1 grades. Age, weight, parity and age at birth of first child are all related to the distribution of mammographic patterns. The combination of these variables with Wolfe grades may identify subsets of the population at very high risk.