Published results on breast cancer and hormone replacement therapy in the Million Women Study are correct.
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Bias↗
Biomedical subjects
E Banks
Publications and source records attributed to E Banks.
Predictors of outcome of mammography in the National Health Service Breast Screening Programme.
BACKGROUND: Little is known about the factors influencing the risk of recall for assessment, invasive diagnostic procedures, and early rescreening after screening mammography. METHODS: From June 1996 to March 1998 women attending screening at 10 National Health Service Breast Screening Programme (NHSBSP) centres completed a self administered questionnaire and were followed up for their screening outcome. RESULTS: 1969 (3.3%) out of 60 443 women aged 50-64 who had never used hormone replacement therapy (HRT) were recalled for assessment but were not diagnosed with breast cancer (defined here as false positive recall). After adjustment for the variation between centres, false positive recall was decreased significantly among women who were likely to have had a previous NHSBSP mammogram (odds ratio (OR) 0.49, 95% confidence interval (95% CI) 0.38 to 0.63 for likely versus unlikely), who were postmenopausal (OR 0.65, 95% CI 0.56 to 0.76 for postmenopausal v premenopausal) and increased significantly for women reporting previous breast surgery (OR 1.64, 95% CI 1.42 to 1.89). Although false positive recall decreased significantly with parity and increasing body mass index, these effects were not large and no significant variation was found with age, education, family history of breast cancer, oral contraceptive use, sterilisation, exercise, smoking, or alcohol consumption. Altogether 655 (1.1%) women had an invasive diagnostic procedure; no personal characteristics were predictive of this outcome, 286(0.5%) were referred for early rescreening, and this was increased significantly by nulliparity and a family history of breast cancer. INTERPRETATION: Premenopausal women, those without a previous NHSBSP mammogram, and women with previous breast surgery have an increased risk of false positive recall by the NHSBSP.
Age Factors↗
Use of hormonal therapy for menopause in nine European countries.
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Age Distribution↗
Epidemiology of breast cancer.
Breast cancer is the commonest cause of cancer death in women worldwide. Rates vary about five-fold around the world, but they are increasing in regions that until recently had low rates of the disease. Many of the established risk factors are linked to oestrogens. Risk is increased by early menarche, late menopause, and obesity in postmenopausal women, and prospective studies have shown that high concentrations of endogenous oestradiol are associated with an increase in risk. Childbearing reduces risk, with greater protection for early first birth and a larger number of births; breastfeeding probably has a protective effect. Both oral contraceptives and hormonal therapy for menopause cause a small increase in breast-cancer risk, which appears to diminish once use stops. Alcohol increases risk, whereas physical activity is probably protective. Mutations in certain genes greatly increase breast-cancer risk, but these account for a minority of cases.
Adult↗
Energy balance and cancer: the role of sex hormones.
Energy balance can affect the risk for hormone-related cancers by altering sex hormone levels. Energy intake and expenditure are difficult to measure in epidemiological studies, but a chronic excess of intake relative to expenditure leads to a high BMI, which can be accurately measured. In premenopausal women obesity has little effect on the serum concentration of oestradiol, but causes an increase in the frequency of anovular menstrual cycles and thus a reduction in progesterone levels; these changes lead to a large increase in the risk for endometrial cancer. but little change, or a small decrease, in the risk for breast cancer. In post-menopausal women oestradiol levels are not regulated by negative feedback, and obesity causes an increase in the serum concentration of bioavailable oestradiol; this factor causes increases in the risk for both endometrial cancer and breast cancer. The development of ovarian cancer appears to be related more strongly to the frequency of ovulation than to direct effects of circulating levels of sex hormones, and BMI is not clearly associated with the risk for ovarian cancer. In men, increasing BMI has little effect on bioavailable androgen levels, and any effect of obesity on prostate cancer risk is small.
Body Mass Index↗
Agreement between general practice prescription data and self-reported use of hormone replacement therapy and treatment for various illnesses.
BACKGROUND: Epidemiological studies of the effects of hormone replacement therapy (HRT) often rely on exposure data and information on past health from self-administered questionnaires. The accuracy with which women report current use of HRT and the specific preparation in use is not known. This study aims to compare aspects of self-reported use of HRT and treatment for various conditions with data from general practice prescription records. METHODS: Reported questionnaire data on use of HRT were compared with those on the general practice prescription record for 570 women participating in the Million Women Study from two general practices in the UK. RESULTS: There was excellent agreement between data from the self-administered questionnaire and the prescription record: 96% agreement (kappa = 0.91) for current use of HRT, 95% agreement (kappa = 0.90) for any use of HRT during the period covered by the prescription record, and 97% agreement (kappa = 0.95) among current users for whether the HRT preparation contained oestrogen alone, combined oestrogen/progestogen, or some other constituents. Among former HRT users who provided questionnaire information on the preparation they used most recently, there was 69% agreement on the proprietary preparation used and 97% agreement (kappa = 0.93) on the hormonal constituents used. Agreement between reported treatment for various conditions and the presence of a prescription appropriate for that condition ranged from 89-99% (kappa 0.53-0.92), and was highest for thyroid disease and asthma. CONCLUSION: Important aspects of use of HRT, such as type of preparation currently being used, are reported very reliably by women completing a self-administered questionnaire.
Drug Prescriptions↗
Overview of the relationship between use of progestogen-only contraceptives and bone mineral density.
OBJECTIVES: To summarise the available epidemiological evidence regarding the relationship between the use of progestogen-only contraceptives and bone mineral density. DESIGN AND METHODS: Overview of the published epidemiological literature. RESULTS: Overall, 17 studies of the use of progestogen-only contraceptives and bone mineral density were identified, involving 1529 women exposed to progestogen-only contraceptives and 2086 controls. Sixty-eight percent of the data relate to the effects of use of depot medroxyprogesterone acetate. Average bone mineral density was reduced in current users of depot medroxyprogesterone acetate compared with non-users, although density in users was within one standard deviation of the mean in non-users. There was significant heterogeneity between the results of different studies (P < 0.0001). The reduction in bone mineral density appeared to be greater at the lumbar spine, femoral neck and ultradistal forearm than at the midshaft of the ulna. Studies involving women with a longer average duration of use of depot medroxyprogesterone acetate displayed greater reductions in bone mineral density compared with studies of women with shorter durations of use. Based on limited data, no difference in bone mineral density was observed between former and never users of depot medroxyprogesterone acetate. Results regarding the effect of levonorgestrel implants were conflicting. Studies of progestogen-only oral contraceptives and the progesterone vaginal ring were small and restricted to lactating women. CONCLUSIONS: Women currently using depot medroxyprogesterone acetate have a lower average bone mineral density than non-users. The magnitude of this effect is uncertain but appears to be greater with longer durations of use.
Adolescent↗
Hormone replacement therapy and the sensitivity and specificity of breast cancer screening: a review.
BACKGROUND: The use of hormone replacement therapy (HRT) is prevalent in the age group invited to routine breast cancer screening in many countries. Previous publications have reported reduced sensitivity and specificity of mammographic breast cancer screening associated with current use of HRT. OBJECTIVES: To review the epidemiological evidence for the relation between use of HRT and the risk of having breast cancer diagnosed between screens (interval breast cancer--sensitivity) and being recalled for assessment after initial mammography with no diagnosis of breast cancer at that screen (false positive recall--specificity). METHODS: Overview of published literature. RESULTS: Eight studies were identified, providing a total of 367 interval cancers and 8878 cases of false positive recall, in women of 50 and over. Overall, the studies showed an increased risk of interval cancer and false positive recall in current users of HRT compared with non-users. Only one study accounted for the essential confounding factors of age and menopause. Furthermore, information on duration and recency of HRT use was not available for most studies. CONCLUSIONS: Studies to date indicate that women using HRT are more likely to experience reduced sensitivity and specificity of breast cancer screening, compared with women not using HRT. However, because results have not been adjusted for crucial confounding factors, the magnitude of these effects is uncertain.
Aged↗
Thapsigargin suppresses phorbol ester-dependent human involucrin promoter activity by suppressing CCAAT-enhancer-binding protein alpha (C/EBPalpha) DNA binding.
Human involucrin (hINV) is a keratinocyte differentiation marker expressed in the suprabasal epidermal layers. In cultured keratinocytes hINV mRNA levels are increased 10-fold by a 24-h treatment with 50 ng/ml PMA, an agent that promotes keratinocyte differentiation. Previous studies show that thapsigargin (TGN), an agent that depletes intracellular calcium stores, inhibits keratinocyte differentiation. In the present study we show that TGN inhibits the PMA-dependent, differentiation-associated, increase in hINV mRNA levels and hINV promoter activity. Inhibition is half-maximal at 10 nM and maximal at 100 nM TGN. Neither basal hINV promoter activity nor glyceraldehyde-3-phosphate dehydrogenase mRNA levels are inhibited. Mutation of a functionally important CAATT-enhancer-binding protein (C/EBP) site within the hINV promoter proximal regulatory region eliminates the regulation, suggesting that TGN may effect C/EBP-dependent promoter activation. Consistent with this hypothesis, TGN inhibits C/EBPalpha-dependent promoter activation via a mechanism that involves inhibition of C/EBPalpha binding to DNA without changing C/EBPalpha protein levels. These results suggest that TGN interferes with hINV expression by interfering with C/EBP transcription-factor function.
Base Sequence↗
N-acetyltransferase 2 and bladder cancer: an overview and consideration of the evidence for gene-environment interaction.
Genetic polymorphism of the carcinogen metabolizing enzyme N-acetyl transferase 2 (NAT2) may influence susceptibility to bladder cancers related to smoking or to occupational exposure to arylamine carcinogens. This article reviews the results of 21 published case-control studies of NAT2 polymorphism and bladder-cancer risk, with a total of 2700 cases and 3426 controls. The published evidence suggests that NAT2 slow acetylator phenotype or genotype may be associated with a small increase in bladder cancer risk. However, given the possibility of selective publication of results from studies that found an excess risk, the current evidence is not sufficient to conclude that there is a real increase in risk. Only five of the 21 studies reported results separately for the effect of NAT2 on bladder cancer risk in smokers and non-smokers. Although the results suggest that the effect may be greater in smokers than in non-smokers, the possibility of publication bias makes these results difficult to interpret. There was insufficient evidence to assess the joint effect of NAT2 and occupational exposure to arylamines on bladder cancer risk. Even if estimates of the effect of NAT2 from published data are correct, studies with around 3000-5000 cases will be needed to confirm them.
Arylamine N-Acetyltransferase↗
Hormone replacement therapy for secondary prevention of coronary heart disease.
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Coronary Disease↗
Hormone replacement therapy: patterns of use studied through British general practice computerized records.
OBJECTIVE: We aimed to describe the longitudinal pattern of hormone replacement therapy (HRT) consumption in a cohort of long-term users (defined as use for >1 year). METHOD: We carried out longitudinal analysis of prescription data derived from GPs' computer records. Subjects were recruited through 15 general practices in the former Oxford, South West and North West Thames Regions that contributed to the VAMP/OPCS general practice research database. All women in the practices aged 45-64 years in September 1991 were identified. Of these, the analysis concerned the 1224 long-term users and 1154 non-user controls who remained in the practices from September 1991 to March 1995; 868 (71%) of the users and 698 (61%) of the controls also provided questionnaire data. RESULTS: The prevalence of HRT use was 15% in 1992, a rise of 16% from 1991. The prevalence of long-term use was 10%; 22% of the cohort identified as taking HRT between April and September 1991 had left the practices or were not taking HRT 1 year later. But for the group defined as long-term users in 1992, the rate of discontinuation was less than 5% per year over the following 2 1/2 years. Users of opposed therapy were 50% more likely to discontinue than users of unopposed therapy. Almost all women who had or had not undergone hysterectomy were taking unopposed or opposed therapy, respectively. Over 80% of prescriptions were for oral therapy. A third of users of either opposed or unopposed therapy changed the formulation during the 4 years of observation, and two-thirds of those who used both forms changed at least once in addition. Two changes were required to accommodate 94% of users. CONCLUSIONS: Once women have taken HRT for a year, their continuation rate is over 95% per annum. Although the majority of women stayed with one formulation, a substantial minority changed formulation quite frequently, three formulations being required to accommodate 94% of long-term users over 4 years. Any trial of HRT use will need to recruit long-term users and allow for change in formulation of HRT in its protocol.
Aged↗
Use of HRT and the subsequent risk of cancer.
At least 20 million women in developed countries are estimated to be currently using hormone replacement therapy (HRT). Almost 100 epidemiological studies have reported on the relationship between the use of HRT and the risk of cancer of female reproductive organs, namely the breast, uterus or ovary. Cancer at these sites is common and there are a priori reasons why the use of hormonal therapy to 'replace' the endogenous production of ovarian hormones after the menopause might increase the risk of these cancers. The available evidence indicates that the risk of breast cancer or endometrial cancer is increased while women are using HRT, the risk increasing with increasing duration of use. Most of the evidence about these cancers relates to use of HRT preparations containing oestrogens alone. The limited evidence about combination therapy, with oestrogens and progestogens, suggests that, compared to oestrogens alone, the effect on the breast is similar, but the effect on the endometrium is diminished, the diminution in risk being greater the more days each month that progestogens are used. The effect of HRT on breast cancer wears off after use ceases and has disappeared largely, if not wholly, within 5 years, whereas the effects on endometrial cancer take longer to wear off, if at all. The breast and endometrial cancers that are diagnosed in HRT users are less aggressive clinically than cancers in never-users but, as yet, there is little reliable information about the relationship between use of HRT and mortality from these cancers. For other cancer sites, the existing data about the effects of HRT are inconclusive. The longer the period of use of HRT, the greater the excess incidence of cancer of the breast and endometrium is likely to be. Use of HRT for short periods of time should have little effect on the incidence of these cancers. The cumulative excess incidence in 1000 women who used HRT for 10 years, beginning at age 50, is estimated to be six for breast cancer, 42 for endometrial cancer in women with an intact uterus using oestrogen therapy alone and about 20 for endometrial cancer in women with an intact uterus using oestrogen-progestogen combinations. The estimate for combined therapy is based on small numbers and may well vary with the type of preparation used. The overall balance between the excess incidence of these cancers and other effects of HRT needs to be evaluated carefully and will require more reliable data than exist at present.
Adult↗
Effect on attendance at breast cancer screening of adding a self administered questionnaire to the usual invitation to breast screening in southern England.
STUDY OBJECTIVE: The primary aim of the research described in this paper was to ascertain whether inclusion of a self administered questionnaire with the usual invitation to routine breast screening affected screening uptake. Secondary aims included establishing appropriate questionnaire distribution and collection methods within the framework of the National Health Service Breast Screening Programme and optimisation of questionnaire design. DESIGN: Randomised study. SETTING: Oxfordshire and West of London Breast Screening Units. PARTICIPANTS/METHODS: 6400 women invited for routine screening mammography were individually randomised to receive either the usual breast screening invitation alone, or to receive the usual invitation accompanied by a self administered questionnaire, to be returned at the time of screening. Participants were then followed up and attendance rates at screening were compared between groups. MAIN RESULTS: Screening attendance rates were similar in women who did and did not receive a questionnaire (71% in each group). Of those who were sent a questionnaire and attended for screening, 77% returned a completed questionnaire. Screening uptake was not affected by the way in which the questionnaire was returned or by whether or not personal details and signed permission for follow up were requested. CONCLUSIONS: The inclusion of a self administered questionnaire accompanying the invitation to breast screening did not adversely affect screening uptake. A high proportion of women completed the questionnaire.
Breast Neoplasms↗
Hormone replacement therapy and high incidence of breast cancer between mammographic screens.
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Breast Neoplasms↗
Catastrophic shoulder dystocia and emergency symphysiotomy.
We present three cases of shoulder dystocia unrelieved by standard maneuvers, including cephalic replacement. Symphysiotomy was performed in an effort to preserve fetal life. All three infants sustained severe neurologic injury and later died. Maternal morbidity including urinary incontinence was significant but responded to treatment. Symphysiotomy may be the only method of relieving some cases of shoulder dystocia, but its role remains unclear because of operator inexperience and maternal morbidity.
Adult↗
Women doctors' use of hormone replacement therapy. High prevalence of use is not confined to doctors.
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England↗
Chronic innominate artery dissection after blunt thoracic trauma: case report.
Blunt innominate chest trauma is relatively rare, with only 70 cases being reported in the surgical literature since 1960. This report describes a 20-year-old male who sustained a blunt chest injury that resulted in an innominate artery dissection. The patient's clinical course and management are discussed, as well as a review of the surgical literature.
Adult↗