D.Y. Wang

Sex hormones in women in rural China and in Britain.

Plasma concentrations of certain hormones linked to breast cancer risk were measured in age-pooled samples from 3,250 rural Chinese women in 65 counties, and 300 British women, all aged 35-64. In age-groups 35-44, 45-54 and 55-64 respectively, mean oestradiol concentrations were 36% (P = 0.043), 90% (P less than 0.001) and 171% (P = 0.001) higher in the British than in the Chinese women, and mean testosterone concentrations were 48% (P less than 0.001), 68% (P less than 0.001) and 53% (P = 0.001) higher in the British than in the Chinese women. The difference in testosterone concentrations between the two countries appeared to be due largely to the lower average body weight in the Chinese women. Sex hormone binding globulin did not differ significantly between the two countries in age groups 35-44 and 45-54, but was 15% (P = 0.002) lower in the British than in the Chinese women at ages 55-64. Prolactin concentrations did not differ significantly between the two countries in any age group.

THE PREVENTION OF BREAST CANCER

The case for treating women at high risk of breast cancer with the anti-oestrogen tamoxifen is presented. This is a logical extension of a screening programme and is scientifically based on the effectiveness of tamoxifen in established disease, the relation between free oestradiol (and other hormone-related factors) to the risk of breast cancer, and the lack of side-effects from tamoxifen treatment. Choice of a high-risk group is critical; a specific trial protocol is outlined.

Relationship between plasma carcinoembryonic antigen and prognosis in women with breast cancer

Abstract The concentration of CEA was measured in plasma from normal women, patients with early breast cancer (before and after mastectomy) and advanced breast cancer. Assays were performed on coded plasma of unknown origin and only when the estimations had been completed was the code broken and the results analysed. The data showed that CEA levels were not of diagnostic value since the proportion of normal women with measurable CEA (35%) was similar to that found in women with early breast cancer (before or after mastectomy). It was also observed that about 30% of subjects had an increased CEA level after mastectomy. The proportion of patients with advanced breast cancer with positive CEA titres was 69%. Patients after mastectomy with CEA levels above 2·5 ng/ml had a significantly (P

The permanent effect of reproductive events on blood prolactin levels and its relation to breast cancer risk: a population study of postmenopausal women

In each of two population-based studies conducted on the Island of Guernsey between 1967-1976 and 1977-1984, respectively, single specimens of blood were taken from over 5000 normal women. From these two studies there were 1173 and 946 postmenopausal women in whom blood prolactin was determined and multivariate analysis was used to establish the association between blood prolactin concentration and possible determinants of risk of breast cancer. Since prolactin levels were log-normally distributed these analyses were done on log-transformed data. The age at menarche or menopause, age at first or last childbirth, length of reproductive life (i.e. time from menarche to menopause) or post-menopausal life (i.e. time from menopause to time of blood sampling), contraceptive use and history of breast cancer were not significantly associated with blood prolactin concentration. Of significance were age, parity, time of blood sampling and assay drift. Ponderosity (Quetelets Index) was positively associated with prolactin concentration and this was significant using a one-tail criterion. Women with a mammographic pattern designated DY by Wolfe had significantly higher prolactin levels than those with N1 patterns. However, the main finding to emerge was that after standardizing for all the other variables increasing parity was related to a step-wise reduction in blood prolactin levels. Since this had occurred in women who had had their last child up to 35 years previously it implies this effect is permanent. It could therefore be that the protective effect on breast cancer risk of multiparity and early first pregnancy could be mediated by such a life-long reduction in blood prolactin levels.

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.

Testosterone, sex hormone-binding globulin, calculated free testosterone, and oestradiol in male vegans and omnivores

Total testosterone (T), total oestradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were measured in plasma samples from fifty-one male vegans and fifty-seven omnivores of similar age. Free T concentration was estimated by calculation. In comparison with the omnivores, the vegans had 7% higher total T (P = 0.250), 23% higher SHBG (P = 0.001), 3% lower free T (P = 0.580), and 11% higher E2 (P = 0.194). In a subset of eighteen vegans and twenty-two omnivores for whom 4 d diet records were available, there were statistically significant correlations between T and polyunsaturated fatty acids (r 0.37), SHBG and fat (r 0.43 for total fat, 0.46 for saturated fatty acids and 0.33 for polyunsaturated fatty acids), and SHBG and alcohol (r-0.39). It is concluded that a vegan diet causes a substantial increase in SHBG but has little effect on total or free T or on E2.

The relationship between blood prolactin levels and risk of breast cancer in premenopausal women

Single specimens of blood have been taken from over 5000 normal volunteer women in each of two sequential (1967-1976, 1977-1984) population-based studied on the Island of Guernsey. Multivariate analysis was used to determine the relationship between prolactin levels and risk factors in breast cancer in 2591 and 1959 premenopausal women in whom blood prolactin had been measured. In both populations the prolactin concentrations appeared to be log-normally distributed and therefore all analyses have been done on log-transformed data. Initially the variables in the statistical model were age at menarche, ages at first and last baby, parity, ponderosity (Quetelet Index), mammographic pattern (as graded by Wolfe), family history of breast cancer, age, menstrual cycle status, time of day of blood sampling, oral contraceptive use, history of breast feeding and methodological changes in the laboratory measurement of prolactin. Of these variables age at menarche, ages at first and last child and family history of breast cancer were found not to be significant and were excluded from the final model. The main finding to emerge was that after standardizing for all the other variables, prolactin levels in the follicular phase were significantly lower than those found at midcycle or during the luteal phase of the menstrual cycle. A peak level of prolactin was found at day 12 of the cycle. Increasing parity was related to a steady decrease in prolactin concentration. Increasing ponderosity was associated with an increased prolactin level as was a DY compared to an N1 mammographic pattern. Women with a history of oral contraceptive use had lowered prolactin concentration. All these effects occurred evenly over the menstrual cycle and were generally found for both data sets. Thus body weight, parity and, indirectly, age at first baby might influence breast cancer risk by being associated with changes in blood prolactin concentration.

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

Serum prolactin (HPr) has been measured in 459 patients 1 day before (HPr-1) and in 433 patients 10 days after (HPr-2) treatment. These came from an unselected sequence of 739 patients with operable breast cancer who had been referred to Guys Hospital over a period of 5 yr. In addition HPr was measured in 100, or more, women at 3, 6 or 12 months after mastectomy. The median levels of either HPr-1 or HPr-2 were higher in pre-menopausal compared with postmenopausal patients (P = 0.03 and 0.06, respectively). Mastectomy was associated with increased serum HPr in both pre- and post-menopausal patients (P less than 0.001 in both cases). Average levels at 3 months, or after, were similar to those found before treatment. Nulliparous women had a higher median amount of HPr-1 than parous which was significant in premenopausal patients (P less than 0.008) whilst HPr-2 levels were not related to parity. Thus the rise in HPr associated with surgery was greater in parous than nulliparous women. Prolactin levels were not related to nodal status or tumour size. However, the amounts of HPR-2 were significantly greater in women with histological grade 3 tumours than those with grade 1 or 2. Standardising for either nodal status, tumour size or histological grade seven situations were found in which HPr-1 or HPr-2 levels were of prognostic significance. Although some of these significant associations could be fortuitous all shared a common feature that the least favourable prognosis was associated with the highest HPr levels.

Ovarian function and adjuvant chemotherapy for early breast cancer.

The effect of cyclophosphamide, methotrexate and fluorouracil (CMF) on ovarian function has been studied in 74 pre-menopausal patients with operable breast cancer. After median follow-up of 47 months, 50, 70 and 80% of 35 patients receiving CMF became permanently amenorrhoeic within 3, 6 and 12 months respectively; in contrast, only 5 in the no treatment (control) group of 39 patients became permanently amenorrhoeic within 12 months. Younger patients (less than 35 years) were more likely to retain or regain menstrual function while on or after CMF treatment. Estimation of ovarian and pituitary hormones in a subset of these women showed that CMF treatment was associated with a decrease in serum oestradiol and progesterone and an increase in serum follicle stimulating hormone and luteinizing hormone to post-menopausal levels. These hormonal changes are consistent with the induction of amenorrhoea during CMF treatment and the absence of resumption of menstrual function after completion of treatment suggests that CMF causes permanent ovarian ablation in a majority of these patients.

Plasma oestradiol and progesterone levels in women with varying degrees of risk of breast cancer.

Abstract Increased risk of breast cancer in pre-menopausal women correlates with sub-normal plasma progesterone values in the luteal phase of the menstrual cycle and a sub-normal excretion of urinary androgen metabolites. Plasma oestradiol values do not vary with risk. In post-menopausal women, plasma oestradiol and progesterone levels are not related to risk.