T Gathani

Hormonal therapy for menopause and breast-cancer risk by histological type: a cohort study and meta-analysis

BACKGROUND Little information is available on how the risk of breast cancer associated with the use of hormone therapy for menopause varies by histological type. We aimed to describe such associations for eight histological types of breast cancer. METHODS Analyses are based on 1 031 224 postmenopausal women recruited in 1996-2001 into a nationwide UK cohort study, and followed for incident cancer and death. Relative risks associated with use of hormone therapy were estimated for eight histological types of breast cancer. FINDINGS During 3.6 million person-years of follow-up, 14 102 breast cancers were diagnosed, of which 13 782 (98%) had histological type recorded: 11 869 (86%) were invasive, including 8007 ductal, 1526 lobular, 365 mixed ductal-lobular, 492 tubular, 71 medullary, and 148 mucinous cancers; and 1913 (14%) were in situ, including 1443 ductal and 86 lobular cancers. The relative risks of invasive breast cancer in current users compared with never users of hormone therapy varied significantly according to tumour histology overall (p<0.0001), for users of oestrogen-only therapy (p=0.0001), and for users of oestrogen-progestagen therapy (p<0.0001). The largest relative risks in current compared with never users of hormone therapy were seen for lobular (relative risk 2.25, 95% CI 2.00-2.52), mixed ductal-lobular (2.13, 1.68-2.70), and tubular cancers (2.66, 2.16-3.28). The relative risks for ductal and mucinous cancers were 1.63 (95% CI 1.55-1.72) and 1.58 (1.08-2.31), respectively. The risk of medullary cancer was not increased (0.74, 0.43-1.28). The relative risk of in-situ disease in current users compared with never users of hormone therapy also varied significantly according to histological type (p=0.03), with a relative risk for lobular carcinoma in situ of 2.82 (1.72-4.63) and 1.56 (1.38-1.75) for ductal carcinoma in situ. The effects of hormone therapy on invasive ductal, lobular, and tubular cancer were generally greater for oestrogen-progestagen therapy than for oestrogen-only therapy, and were attenuated with increasing body-mass index (BMI). INTERPRETATION The risks associated with use of hormone therapy for menopause differ by histological type of breast cancer, and are substantially attenuated with increasing BMI.

Night Shift Work and Breast Cancer Incidence: Three Prospective Studies and Meta-analysis of Published Studies

Background: It has been proposed that night shift work could increase breast cancer incidence. A 2007 World Health Organization review concluded, mainly from animal evidence, that shift work involving circadian disruption is probably carcinogenic to humans. We therefore aimed to generate prospective epidemiological evidence on night shift work and breast cancer incidence. Methods: Overall, 522 246 Million Women Study, 22 559 EPIC-Oxford, and 251 045 UK Biobank participants answered questions on shift work and were followed for incident cancer. Cox regression yielded multivariable-adjusted breast cancer incidence rate ratios (RRs) and 95% confidence intervals (CIs) for night shift work vs no night shift work, and likelihood ratio tests for interaction were used to assess heterogeneity. Our meta-analyses combined these and relative risks from the seven previously published prospective studies (1.4 million women in total), using inverse-variance weighted averages of the study-specific log RRs. Results: In the Million Women Study, EPIC-Oxford, and UK Biobank, respectively, 673, 28, and 67 women who reported night shift work developed breast cancer, and the RRs for any vs no night shift work were 1.00 (95% CI = 0.92 to 1.08), 1.07 (95% CI = 0.71 to 1.62), and 0.78 (95% CI = 0.61 to 1.00). In the Million Women Study, the RR for 20 or more years of night shift work was 1.00 (95% CI = 0.81 to 1.23), with no statistically significant heterogeneity by sleep patterns or breast cancer risk factors. Our meta-analysis of all 10 prospective studies included 4660 breast cancers in women reporting night shift work; compared with other women, the combined relative risks were 0.99 (95% CI = 0.95 to 1.03) for any night shift work, 1.01 (95% CI = 0.93 to 1.10) for 20 or more years of night shift work, and 1.00 (95% CI = 0.87 to 1.14) for 30 or more years. Conclusions: The totality of the prospective evidence shows that night shift work, including long-term shift work, has little or no effect on breast cancer incidence.

Ethnic differences in breast cancer incidence in England are due to differences in known risk factors for the disease: prospective study

Background:In the United Kingdom, breast cancer incidence is lower in South Asian and Black women than in White women, but the extent to which this is due to known risk factors is unknown. In a large prospective study, we describe breast cancer incidence by ethnicity, before and after adjustment for known risk factors for the disease.Methods:Women were recruited into the Million Women Study in 1996–2001, when information on reproductive and lifestyle factors known to influence the risk of breast cancer was obtained. Ethnicity was determined from study questionnaires and hospital admission data. Cox regression models were used to calculate adjusted relative risks (RR) for incident breast cancer in South Asians and Blacks compared with Whites.Results:Analyses included 5877 South Asian, 4919 Black, and 1 038 144 White women in England. The prevalence of 8 out of the 9 risk factors for breast cancer examined, differed substantially by ethnicity (P<0.001 for each), such that South Asian and Black women were at a lower risk of the disease than White women. During 12.2 years of follow-up incident breast cancer occurred in 217 South Asians, 180 Blacks, and 45 191 Whites. As expected, breast cancer incidence was lower in South Asians (RR=0.82, 95% CI 0.72–0.94) and Blacks (RR=0.85, 0.73–0.98) than in Whites when the analyses were adjusted only for age and region of residence. However, after additional adjustment for the known risk factors for the disease, breast cancer incidence was similar to that of Whites, both in South Asians (0.95, 0.83–1.09) and in Blacks (0.91, 0.78–1.05).Conclusion:South Asian and Black women in England have lower incidence rates of breast cancer than White women, but this is largely, if not wholly, because of differences in known risk factors for the disease.

Birth weight and adult cancer incidence: large prospective study and meta-analysis

BACKGROUND Most evidence about associations between birth weight and adult cancer risk comes from studies linking birth records to cancer registration data, where information on known risk factors for cancer is generally lacking. Here, we report on associations between birth weight and cause-specific cancer risk in a large cohort of UK women, and investigate how observed associations are affected by other factors. METHODS A total of 453 023 women, born in the 1930s and 1940s, reported their birth weight, maternal smoking, parental heights, age at menarche, adult height, adult smoking, and many other personal characteristics. They were followed for incident cancer. Using Cox regression, relative risks by birth weight were estimated for cancers with more than 1500 incident cases, adjusting for 17 potential confounding factors, individually and simultaneously. RESULTS Birth weight reported in adulthood was strongly correlated with that recorded at birth (correlation coefficient = 0.78, P < 0.0001). Reported birth weight was associated with most of the potential confounding factors examined, the strongest association being with adult height. After 9.2 years follow-up per woman, 39 060 incident cancers were registered (4414 colorectal, 3175 lung, 1795 malignant melanoma, 14 542 breast, 2623 endometrial, 2009 ovarian, 1565 non-Hodgkin lymphoma, and 8937 other cancers). Associations with birth weight were null or weak and reduced after adjustment by adult height (P[trend] > 0.01 for every cancer, after adjustment). In contrast, adult height was strongly related to the risk of every cancer except lung cancer, after adjusting for birth weight and other factors (P[trend] < 0.0001 for most cancers). For lung cancer, adjusting for smoking reduced the association with birth weight. Meta-analyses were dominated by our findings. CONCLUSION Birth weight and adult height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women.Birth weight and height are correlated and likely to be markers of some aspect of growth that affects cancer risk in adulthood. However, birth weight adds little, if any, additional information to adult height as a predictor of cancer incidence in women.

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

IntroductionEpidemiological 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.Methods1.3 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.ResultsA 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%, κ = 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%, κ = 0.8).ConclusionThere 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.

Heterogeneity of colorectal cancer risk by tumour characteristics: Large prospective study of UK women

Associations between behavioural and other personal factors and colorectal cancer risk have been reported to vary by tumour characteristics, but evidence is inconsistent. In a large UK‐based prospective study we examined associations of 14 postulated risk factors with colorectal cancer risk overall, and across three anatomical sites and four morphological subtypes. Among 1.3 million women, 18,518 incident colorectal cancers were identified during 13.8 (SD 3.4) years follow‐up via record linkage to national cancer registry data. Cox regression yielded adjusted relative risks. Statistical significance was assessed using correction for multiple testing. Overall, colorectal cancer risk was significantly associated with height, body mass index (BMI), smoking, alcohol intake, physical activity, parity and menopausal hormone therapy use. For smoking there was substantial heterogeneity across morphological types; relative risks around two or greater were seen in current smokers both for signet ring cell and for neuroendocrine tumours. Obese women were also at higher risk for signet ring cell tumours. For adenocarcinomas, the large majority of colorectal cancers in the cohort, all risk factor associations were weak. There was little or no heterogeneity in risk between tumours of the right colon, left colon and rectum for any of the 14 factors examined. These epidemiological findings complement an emerging picture from molecular studies of possible different developmental pathways for different tumour types.

Hospital costs in relation to body-mass index in 1·1 million women in England: a prospective cohort study

Summary Background Excess weight is associated with poor health and increased health-care costs. However, a detailed understanding of the effects of excess weight on total hospital costs and costs for different health conditions is needed. Methods Women in England aged 50–64 years were recruited into the prospective Million Women Study cohort in 1996–2001 through 60 NHS breast cancer screening centres. Participants were followed up and annual hospital costs and admission rates were estimated for April 1, 2006, to March 31, 2011, in relation to body-mass index (BMI) at recruitment, overall and for categories of health conditions defined by the International Classification of Diseases 10th revision chapter of the primary diagnosis at admission. Associations of BMI with hospital costs were projected to the 2013 population of women aged 55–79 years in England. Findings 1 093 866 women who provided information on height and weight, had a BMI of at least 18·5 kg/m2, and had no previous cancer at recruitment, were followed up for an average of 4·9 years from April 1, 2006 (12·3 years from recruitment), during which time 1·84 million hospital admissions were recorded. Annual hospital costs were lowest for women with a BMI of 20·0 kg/m2 to less than 22·5 kg/m2 (£567 per woman per year, 99% CI 556–577). Every 2 kg/m2 increase in BMI above 20 kg/m2 was associated with a 7·4% (7·1–7·6) increase in annual hospital costs. Excess weight was associated with increased costs for all diagnostic categories, except respiratory conditions and fractures. £662 million (14·6%) of the estimated £4·5 billion of total annual hospital costs among all women aged 55–79 years in England was attributed to excess weight (BMI ≥25 kg/m2), of which £517 million (78%) arose from hospital admissions with procedures. £258 million (39%) of the costs attributed to excess weight were due to musculoskeletal admissions, mainly for knee replacement surgeries. Interpretation Excess body weight is associated with increased hospital costs for middle-aged and older women in England across a broad range of conditions, especially knee replacement surgery and diabetes. These results provide reliable up-to-date estimates of the health-care costs of excess weight and emphasise the need for investment to tackle this public health issue. Funding Cancer Research UK; Medical Research Council; National Institute for Health Research.

Disability and participation in breast and bowel cancer screening in England: a large prospective study

Background:There is limited information about participation in organised population-wide screening programmes by people with disabilities.Methods:Data from the National Health Service routine screening programmes in England were linked to information on disability reported by the Million Women Study cohort participants.Results:Of the 473 185 women offered routine breast or bowel cancer screening, 23% reported some disability. Women with disabilities were less likely than other women to participate in breast cancer screening (RR=0.64, 95% CI: 0.62–0.65) and in bowel cancer screening (RR=0.75, 0.73–0.76). Difficulties with self-care or vision were associated with the greatest reduction in screening participation.Conclusion:Participation in routine cancer screening programmes in England is reduced in people with disabilities and participation varies by type of disability.

Cohort Profile: the Million Women Study.

The Million Women Study started recruiting participants over 20 years ago, in 1996. The initial stimulus was to obtain robust prospective information on the risk of breast cancer associated with use of different types of menopausal hormone therapy (HT). When planning the necessary largescale prospective study, an equally important aim was to obtain reliable information on the effects of other potentially modifiable factors that affect women’s health as they age. In the early 1990s use of HT increased rapidly in the UK and elsewhere, stimulated in part by claims that use of HT could improve general well-being and increase life expectancy. By the mid-1990s, however, worldwide evidence was beginning to show that HT preparations increased breast cancer risk, though there was little information about the effect of the type of HT most commonly used in Europe, containing both oestrogens and progestagens. It was also clear that women born in the 1940s, who reached adulthood in the 1960s, had considerably different lifestyles compared with previous generations. For example, large proportions had begun smoking and using oral contraceptives as teenagers and young adults, and the long-term effects of these behaviours could not be studied reliably until the 1990s. At the same time there was growing concern about the effects of the increasing prevalence of obesity, and claims that other factors such as diet had important effects on health, all of which required largescale prospective evidence. The UK National Health Service (NHS) provides extraordinarily efficient ways of establishing and maintaining long-term follow-up for large prospective epidemiological studies. Over 99% of the UK population, and all Million Women Study participants, are registered with the NHS, and every individual has a unique NHS number. Electronic linkage, using each individual’s NHS number, to routinely collected NHS databases provides virtually complete follow-up information about deaths, emigrations, cancer registrations and hospital admissions. The NHS Breast Screening Programme invites all UK women registered with the NHS, of a specified age, for free routine breast screening every 3 years. In 1996–2001 the programme routinely invited women aged 50–64 years for mammographic screening, by sending each individual a letter offering them a specific date and time at a specific screening centre. In 66 NHS screening centres, the Million Women Study recruitment questionnaire was included with the invitation letter for screening. Pilot studies in 1994–96 had shown that inclusion of a questionnaire with the invitation did not affect uptake of breast screening. The coordinating centre for the Million Women Study is based in the Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford.

Impact of hormone replacement therapy on breast cancer

The use of hormone replacement therapy (HRT) and its effect on women’s health are contentious issues and have been for as long as HRT has been prescribed. The use of HRT for the treatment of the symptoms of menopause is widespread and well recognized. However, the exposure to exogenous hormones in postmenopausal women and the subsequent risk of cancer in general, and breast cancer in particular, have been of interest.