PubMed Health⌕ Search

Biomedical subjects

R D Bulbrook

Publications and source records attributed to R D Bulbrook.

At least 19 recordsLinked to original sources
PubMed2000

Urinary androgens and breast cancer risk: results from a long-term prospective study based in Guernsey.

Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospective study to determine the relationship between the urinary androgen metabolites, androsterone (A) and aetiocholanolone (E), and risk of breast cancer. During the first 10 years of the study the concentration of urinary A and E was determined in 1887 of the urine specimens. In 1971 we reported that subnormal amounts of urinary A and E were associated with a significantly increased risk of breast cancer. The cohort has been followed regularly during the 37 years since inception of the study and, by May 1998, 248 women had been diagnosed with breast cancer. Urinary androgen metabolites had been measured in 116 of these cases. Analysis of these data confirmed that women diagnosed in the first decade of the study were more likely to have low levels of urinary androgen metabolites. In the following decades, however, those who developed breast cancer were more likely to have manifested an increased A and E excretion. The reversal in the relationship between androgen metabolite excretion and risk suggests that age, or probably more importantly, menopausal status at diagnosis is an important modifying factor. Dichotomizing at age 50 it was found that in the younger age group (predominantly premenopausal) the rate ratios in the lowest tertile of A or E excretion were two- to threefold greater than for those in the highest tertile (chi2(1) = 3.57; P = 0.06: chi2(1) = 4.70; P = 0.03 for A and E respectively). In contrast, in the older age group comprising predominantly post-menopausal women, the rate ratios associated with the lowest tertile of A or E were half that of those in the highest tertile (chi2(1) = 4.10; P = 0.04; chi2(1) = 8.72; P = 0.003 for A and E respectively). This suggests that there may be different endocrine promotional factors for pre-and post-menopausal breast cancer. Hormonal risk factors may vary during the lifetime of an individual woman and this may have profound consequences for prevention strategies.

Age Factors↗
PubMed1997

Breast cancer risk is positively associated with height.

Inter- and intra-national epidemiological studies point to an association between socio-economic status and breast cancer risk. Although there is no direct evidence, the most favoured reason for this relationship is nutritional. An enhanced dietary status, especially during childhood, would be reflected in adult body build. It is, therefore, surprising that there is uncertainty in the literature concerning the association between height and breast cancer risk. In reviewing the publications on this topic it became apparent that case-control studies which found no association between height and risk tended to use self-reported height. In contrast reports claiming a significant, and positive, correlation tended to use heights which were measured by the investigators. In a prospective study we found in a cohort of 2731 ostensibly normal women that, although there was a highly significant linear correlation between self-reported and measured height, the shortest women over-estimated their height whilst the tallest volunteers under-estimated theirs. The significance of crude relative risk and height in this cohort was markedly attenuated when self-reported height was used compared to measured height. Such a systematic error could have a profound effect on the conclusions of studies in this field which relied on self-reporting and could explain the conflicting reports in the literature.

Adult↗
PubMed1996

Ovarian irradiation and prednisone following surgery and radiotherapy for carcinoma of the breast.

Following mastectomy, patients aged 35 to 76 years with operable breast cancer underwent postoperative irradiation of the chest wall and regional lymph nodes. They were then assigned at random to receive no further therapy (NT), ovarian irradiation (R) 2000 rads in 5 days, or ovarian irradiation in the same dosage plus prednisone (R + P) 7.5 mg daily for up to five years. A total of 703 eligible patients received the randomly assigned treatment. The median follow up was 21 years with a range of 14 to 25 years. Overall, there was a delay in recurrence (p = 0.03) and survival was prolonged (p = 0.19) for patients who received R, but in neither case was the difference significant after adjusting for the multiplicity in our data. Overall, patients who received R + P experienced a significant delay in recurrence (p = 0.0003) and a significantly prolonged survival (p = 0.005), even after adjusting for multiple comparisons. In premenopausal patients who received R, the recurrence of breast cancer was delayed and survival prolonged, but not significantly. In premenopausal women aged 45 years or more, R + P therapy significantly prolonged survival (p = 0.0004), while the delay in recurrence although significant (p = 0.02) was only marginally so after allowance for multiple comparisons. No value was demonstrated for ovarian irradiation with or without prednisone therapy in postmenopausal patients. A new finding in this review was that contralateral breast cancer as the first failure was reduced by R + P compared to NT in the overall group.

Adult↗
PubMed1996

A prospective study of urinary oestrogen excretion and breast cancer risk.

To test the hypothesis that high levels of endogenous oestrogens increase the risk for developing breast cancer, concentrations of oestrone, oestradiol and oestriol were measured in 24 h urine samples from 1000 women participants in a prospective study of breast cancer on the island of Guernsey. Sixty-nine subjects were diagnosed with breast cancer subsequent to urine collection. Among women who were premenopausal at the time of urine collection, cases excreted less oestrogen than controls; the odds ratios (95% CI) for breast cancer in the middle and upper thirds of the distribution of oestrogen excretion, in comparison with the lower third (reference group, assigned odds ratio = 1.0), were 0.5(0.2-1.2) and 0.4(0.2-1.1) respectively for oestrone, 0.8(0.4-1.8 and 0.4(0.2-1.1) for oestradiol, 0.7(0.3-1.6) and 0.7(0.3-1.6) for oestriol and 0.9(0.4-2.0) and 0.5(0.2-1.3) for total oestrogens. Among women who were post-menopausal at the time of urine collection, the trend was in the opposite direction, with an increase in risk associated with increased oestrogen excretion; the odds ratios were 0.9(0.3-2.2) and 1.1(0.5-2.8) for oestrone, 0.8(0.3-2.3) and 1.9(0.8-4.6) for oestradiol, 1.5(0.6-3.9) and 1.8(0.7-4.6) for oestriol and 0.9(0.4-2.6) and 1.9(0.7-4.7) for total oestrogens. The trends of increasing risk with increasing oestrogen excretion among post-menopausal women were statistically significant for oestradiol (P = 0.022) and for total oestrogens (P = 0.016). We conclude that high levels of endogenous oestrogens in post-menopausal women are associated with increased breast cancer risk, but that the relationship of oestrogens in premenopausal women with risk is unclear.

Adult↗
PubMed1995

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.

Adult↗
PubMed1993

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

In 1968-1975, a cohort of 5,100 ostensibly healthy women was established on the island of Guernsey, England, for investigation of the influence of hormonal factors on breast cancer. At the women's entry into the study, blood samples were drawn from each participant, and each woman completed a questionnaire that provided information on established risk indicators in human mammary carcinogenesis. Plasma copper levels were measured in 46 breast cancer cases diagnosed an average of 11 years (standard deviation (SD), 4) after entry into the study cohort and in an age-stratified random sample of 138 women drawn from the total initial cohort at risk. Plasma copper levels were 1.31 mg/liter (SD, 0.37) in the cases and 1.26 mg/liter (SD, 0.36) in the controls; the 95% confidence interval for the overall difference was -0.07 to 0.17. A U-shaped relation between premorbid plasma copper levels and the risk of developing breast cancer was seen. Adjusted odds ratios for breast cancer were 1.8, 1.0, 1.6, and 3.2, respectively, in the four quartiles of the copper distribution. No major changes in the risk estimates were observed when statistical evaluation was restricted to cases diagnosed more than 10 years after collection of blood samples.

Adult↗
PubMed1993

The association of height, weight, menstrual and reproductive events with breast cancer: results from two prospective studies on the island of Guernsey (United Kingdom).

The association with breast cancer of menstrual and reproductive events, family history of breast cancer, and body size have been studied on two cohorts of 6,706 volunteers on the island of Guernsey (United Kingdom), 168 of whom had breast cancer detected during follow-up. The median follow-up time of the non-cases was 21 years in the first study and 10 years in the second. A time-dependent Cox regression model was fitted to the data with age as the time-dependent variable in order to represent the effect of changing menopausal status. Other variables examined in the model were age at menarche, parity, age at first birth, family history of breast cancer, height, weight (both directly measured), relative weight (weight [kg]/height[m]), and Quetelet's body mass index (weight[kg]/height[m]2). Interactions between age and all other covariates also were examined. Family history was found to be the most important risk factor for women aged less than 51 years (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 2.0-6.0), and intervals between menarche and first birth longer than 14 years were found to increase significantly the risk of breast cancer in women older than 61 years (RR = 2.4, CI = 1.3-4.4). Height was the only indicator of body size which was associated significantly with risk of breast cancer, the estimated regression coefficient indicating an increase in risk of about 70 percent for women on the 90th centile of height relative to those on the 10th centile. A survey of the literature showed that the association between risk of breast cancer and height was found in those studies which used direct measurements of height but not in others which used self-reported values.

Age Factors↗
PubMed1992

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.

Adolescent↗
PubMed1992

Endocrinological aspects of benign breast disease.

The search for an hormonal abnormality as a key determinant of risk of benign breast disease has proved to be as fruitless as that for breast cancer. In both conditions, the initial lesion is likely not to be mediated by the endocrine system. Once normal epithelial cells have been diverted to either a benign or malignant pathway, variations within the normal hormonal range may be sufficient to account for the clinical and biological manifestations of both conditions.

Animals↗
PubMed1991

A comparison of epidemiological characteristics in breast cancer patients and normal women in Great Britain and Japan: results of a prospective study.

The epidemiological characteristics of normal women and women with early breast cancer in Great Britain were prospectively compared with similar subjects from Japan. The study consisted of 204 women with early breast cancer and 792 normal controls from Great Britain and 200 breast cancers and 335 Japanese controls. The risk factors examined were age, height and weight, menopausal status, age at menarche and menopause, parity, age at first birth, use of oral contraceptives, and family history of breast cancer. The cancers and cases were divided into pre- and postmenopausal groups. There was a striking trend for a protective effect of multiparity in both countries and a weak but inconstant protective effect of age at first birth. In premenopausal British women increase in body mass was significantly associated with a decreased risk of breast cancer but this association was not found for postmenopausal women or in the Japanese women. The results showed that the classical risk factors did not fully account for the differences in breast cancer risk between Great Britain and Japan. The possibility that aetiological factors might be changing warrants investigation.

Adult↗
PubMed1991

Geographical variation in endocrine function and its relation to breast cancer incidence: some general considerations.

Abnormalities in endocrine function are not a determinant of risk of breast cancer within countries, and racial differences in this function do not explain geographical variation in risk. It is suggested that hormonal status is related to tumor growth rates and hence to age at diagnosis, recurrence rates after primary treatment, and survival. Such evidence as there is points in this direction, but it still remains to be finally established whether the disease runs a similar course in all countries when patients are standardised for factors known to affect prognosis.

Breast Neoplasms↗
PubMed1991

Blood concentrations of estradiol and sex hormone-binding globulin in relation to age at menarche in premenopausal British and Japanese women.

In a cross-sectional study, serum estradiol (E2) and sex hormone-binding globulin (SHBG) concentrations were not significantly related to age at menarche in premenopausal British women in the luteal or follicular phases of the cycle. In Japanese subjects in the luteal phase, a marginally higher concentration of E2 was observed in those who had undergone an early rather than a late menarche. In British women, previous oral contraceptive users had significantly lower luteal phase E2 concentrations than never users.

Adult↗
PubMed1991

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.

Adult↗
PubMed1991

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.

Adult↗