• Breast cancer histological classification: agreement between the Office for National Statistics and the National Health Service Breast Screening Programme.

    3 July 2018

    INTRODUCTION: Epidemiological studies rely on data supplied by central cancer registration sources to be timely, accurate and complete. Validation studies of such data at a national level are limited. Data collected for the Million Women Study was used to compare the level of agreement between the Office for National Statistics (ONS) and the National Health Service Breast Screening Programme (NHSBSP) in the recording of incident screen-detected breast cancer histology between 1996 and 2001. METHODS: 1.3 million women aged 50 to 64 years were recruited into the Million Women Study cohort via the NHSBSP. Incident screen-detected breast cancer histologies were notified separately by the ONS and NHSBSP. ICD-10 and ICD-02 ONS codes and NHSBSP histology data were similarly coded to allow for comparison in terms of cancer invasiveness and morphology. The statistical outcome measures are percentage agreement and the kappa statistic. RESULTS: A total of 5,886 incident screen-detected breast cancers were available for analysis. Of the 5,886 screen-detected cancers reported by the ONS and NHSBSP, 5,684 (96.6%, kappa = 0.9) agreed in terms of the degree of invasiveness. Of the 5,458 cancers that had been assigned a specific morphology code, there was exact agreement between the ONS and the NHSBSP in 4,922 cases (90.2%, kappa = 0.8). CONCLUSION: There is an excellent level of agreement between the ONS and NHSBSP in the recording of the histology of screen-detected breast cancer. From these results it is not possible to comment on which source of data is the more or less accurate, although the differences are very small.

  • Predictors of outcome of mammography in the National Health Service Breast Screening Programme.

    3 July 2018

    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.

  • Comparison of various characteristics of women who do and do not attend for breast cancer screening.

    3 July 2018

    BACKGROUND: Information regarding the characteristics and health of women who do and do not attend for breast cancer screening is limited and representative data are difficult to obtain. METHODS: Information on age, deprivation and prescriptions for various medications was obtained for all women at two UK general practices who were invited to breast cancer screening through the National Health Service Breast Screening Programme. The characteristics of women who attended and did not attend screening were compared. RESULTS: Of the 1064 women invited to screening from the two practices, 882 (83%) attended screening. Screening attenders were of a similar age to non-attenders but came from significantly less deprived areas (30% of attenders versus 50% of non-attenders came from the most deprived areas, P < 0.0001) and were more likely to have a current prescription for hormone replacement therapy (32% versus 19%, P < 0.0001). No significant differences in recent prescriptions of medication for hypertension, heart disease, hypercholesterolaemia, diabetes mellitus, asthma, thyroid disease or depression/anxiety were observed between attenders and non-attenders. CONCLUSION: Women who attend the National Health Service Breast Screening Programme come from less deprived areas and are more likely to have a current prescription for hormone replacement therapy than non-attenders, but do not differ in terms of age or recent prescriptions for various other medications.

  • Agreement between general practice prescription data and self-reported use of hormone replacement therapy and treatment for various illnesses.

    3 July 2018

    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.

  • The Million Women Study: design and characteristics of the study population. The Million Women Study Collaborative Group.

    3 July 2018

    OBJECTIVES: To describe the design of the Million Women Study and the characteristics of the study population. STUDY DESIGN: Population-based cohort study of women aged 50-64 in the UK. SETTING: Women are asked to join the Million Women Study when they are invited to routine screening for breast cancer at 61 of the screening centres of the UK National Health Service Breast Screening Programme (NHSBSP). An estimated 71% of women screened by the NHSBSP return a completed questionnaire. PARTICIPANTS: 800 000 women were recruited between May 1996 and June 1999, and it is planned that an additional 200 000 will be recruited by the year 2000. RESULTS: The characteristics of the first 121 000 women recruited into the Million Women Study are described here. At recruitment 33% of the study population were currently using hormone replacement therapy and 47% had used it at some time. Over half (54%) had used oral contraceptives, and 18% were current smokers at the time of recruitment. Before they were screened 1.4% of the women had been diagnosed with breast cancer in the past, 6% had a mother with a history of breast cancer and 3.7% had a sister with a history of breast cancer. It is estimated that 1 million women will have been recruited by early in the year 2000, and that by the end of the year 2002 there will be 5000 screen-detected breast cancers and 23 000 deaths in the cohort, the majority of which will be attributed to cancer (12 600 deaths) and circulatory disease (8000 deaths). CONCLUSIONS: By the end of the year 2002, the Million Women Study will have sufficient statistical power to detect relative risks of 0.8 or less, or of 1.2 or more in current users compared with never users of hormone replacement therapy for mortality from breast cancer, colorectal cancer, lung and ovarian cancer, ischaemic heart disease and stroke.

  • Use of HRT and the subsequent risk of cancer.

    3 July 2018

    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.

  • Overview of the epidemiology of immunodeficiency-associated cancers.

    3 July 2018

    Immunodeficiency, be it congenital, therapeutic, or infectious in origin, increases the risk of certain, but not all, types of cancer. A common feature of these cancers is that specific infectious agents appear to be important in their etiology, not only in immunodeficient subjects but also in the general population. People with acquired immunodeficiency syndrome (AIDS) are at an increased risk of Kaposi's sarcoma, non-Hodgkin's lymphoma, Hodgkin's disease, squamous cell carcinoma of the conjunctiva, and childhood leiomyosarcoma. It is striking that most of these cancers have been associated with specific human herpesvirus (HHV) infections: HHV-8 with Kaposi's sarcoma and the closely related Epstein-Barr virus with non-Hodgkin's lymphoma, Hodgkin's disease, and possibly also with childhood leiomyosarcoma. Moreover, similar associations between these viruses and cancer have been found, albeit inconsistently, in people who are not immunosuppressed. Further research is needed to establish whether the risk of other cancers is also increased in people with AIDS, although, if so, the cancers are likely to be rare or to have comparatively small associated relative risks. Existing evidence suggests that there may be no marked increase in the risk of two common cancers that are known to be caused by infectious agents--hepatocellular carcinoma and invasive carcinoma of the uterine cervix. The apparent lack of an increase in invasive cervical cancer is unexpected and needs further investigation, especially since the prevalence of cervical infection with human papillomaviruses and of low-grade preneoplastic changes in the cervical epithelium is increased in women with AIDS. With the prospect of improved survival in people with AIDS, the effect of immunosuppression on cancer is likely to become an increasingly important issue.

  • Socioeconomic differences in reproductive behaviour.

    3 July 2018

    There are marked socioeconomic variations in the risk of female reproductive cancers. We examine here data from the World Fertility Surveys, the Demographic and Health Surveys, and other national surveys, to assess whether these variations in cancer risk might be explained, at least in part, by socioeconomic variations in reproductive behaviour. There were marked socioeconomic differentials in achieved parity, age at first birth, final childlessness, duration of breastfeeding, and possibly also age at menopause. These differentials were present in almost all settings: countries with low and high levels of modernization, and countries with low and high levels of fertility. In general, women of higher socioeconomic status and with more education had lower fertility and later age at first birth, but a greater prevalence of childlessness, shorter duration of breastfeeding and later age at menopause. However, the size and even the direction of these differentials varied markedly from country to country according to its level of economic development and, within each country, from generation to generation of women. It is possible that some of these socioeconomic differences may be narrowing in recent generations in Western countries. There was little evidence of socioeconomic variations in age at menarche. The observed socioeconomic differentials in most aspects of reproductive behaviour could potentially account for some of the socioeconomic variation in the risk of female reproductive cancers. However, this relationship could not be assessed directly because such analysis would require birth-cohort-specific data on socioeconomic variations in reproductive behaviour and in cancer risks. Unfortunately, these data are not available.