A comparative analysis of risk factor associations with interval and screen-detected breast cancers: A large UK prospective study.

The associations of certain factors, such as age and menopausal hormone therapy, with breast cancer risk are known to differ for interval and screen-detected cancers. However, the extent to which associations of other established breast cancer risk factors differ by mode of detection is unclear. We investigated associations of a wide range of risk factors using data from a large UK cohort with linkage to the National Health Service Breast Screening Programme, cancer registration, and other health records. We used Cox regression to estimate adjusted relative risks (RRs) and 95% confidence intervals (CIs) for associations between risk factors and breast cancer risk. A total of 9421 screen-detected and 5166 interval cancers were diagnosed in 517,555 women who were followed for an average of 9.72 years. We observed the following differences in risk factor associations by mode of detection: greater body mass index (BMI) was associated with a smaller increased risk of interval (RR per 5 unit increase 1.07, 95% CI 1.03-1.11) than screen-detected cancer (RR 1.27, 1.23-1.30); having a first-degree family history was associated with a greater increased risk of interval (RR 1.81, 1.68-1.95) than screen-detected cancer (RR 1.52, 1.43-1.61); and having had previous breast surgery was associated with a greater increased risk of interval (RR 1.85, 1.72-1.99) than screen-detected cancer (RR 1.34, 1.26-1.42). As these differences in associations were relatively unchanged after adjustment for tumour grade, and are in line with the effects of these factors on mammographic density, they are likely to reflect the effects of these risk factors on screening sensitivity.

The burden of risk factors for non-communicable disease in rural Bihar, India: a comparative study with national health surveys.

BACKGROUND: The incidence of non-communicable diseases (NCDs) is increasing in rural India. The National Family Health Survey-5 (NFHS-5) provides estimates of the burden of NCDs and their risk factors in women aged 15-49 and men aged 15-54 years. The aim of this study is to estimate the prevalence of hypertension and body-mass index (BMI) in adults aged 35-70 years in rural India and to compare these estimates, where age ranges overlap, to routinely available data. METHODS: The Non-Communicable Disease in Rural India (NCDRI) Study was a cross-sectional household survey of 1005 women and 1025 men aged 35-70 conducted in Bihar in July 2019. Information was collected on personal characteristics, self-reported medical history and physical measurements (blood pressure, height and weight). Prevalence estimates for hypertension (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, or diagnosed and treated for hypertension), and for underweight (body-mass index < 18.5 kg/m2), normal weight (18.5-25.0 kg/m2) and overweight (≥ 25.0 kg/m2) were calculated. Where age ranges overlapped, estimates from the NCDRI Study were compared to the NFHS-5 Survey. RESULTS: In the NCDRI Study, the estimated prevalence of hypertension was 27.3% (N = 274) in women and 27.6% (N = 283) in men aged 35-70, which was three-times higher in women and over two-times higher in men than in the NFHS-5 Survey. One-quarter (23.5%; N = 236) of women and one-fifth (20.2%; N = 207) of men in the NCDRI Study were overweight, which was approximately 1.5 times higher than in the NFHS-5 Survey. However, where age groups overlapped, similar age-standardized estimates were obtained for hypertension and weight in both the NCDRI Study and the NFHS-5 Survey. CONCLUSION: The prevalence of NCDs in rural India is higher than previously reported due to the older demographic in our survey. Future routine national health surveys must widen the age range of participants to reflect the changing disease profile of rural India, and inform the planning of health services.

Understanding breast cancer as a global health concern.

Breast cancer is now the most commonly diagnosed cancer in the world. The most recent global cancer burden figures estimate that there were 2.26 million incident breast cancer cases in 2020 and the disease is the leading cause of cancer mortality in women worldwide. The incidence is strongly correlated with human development, with a large rise in cases anticipated in regions of the world that are currently undergoing economic transformation. Survival, however, is far less favourable in less developed regions. There are a multitude of factors behind disparities in the global survival rates, including delays in diagnosis and lack of access to effective treatment. The World Health Organization's new Global Breast Cancer Initiative was launched this year to address this urgent global health challenge. It aims to improve survival across the world through three pillars: health promotion, timely diagnosis, and comprehensive treatment and supportive care. In this article, we discuss the key challenges of breast cancer care and control in a global context.

Detailed breast cancer pathology data for large-scale studies - access and completeness in NSW, Australia.

OBJECTIVES: We sought to determine the ease with which breast cancer pathology data could be ascertained for a large cohort of Australian women, to support epidemiological research. METHOD: We assessed a range of options for accessing breast cancer pathology data. Manual review of the pathology report provided to the New South Wales Cancer Registry (NSWCR) was considered most feasible, complete and reliable. Incident breast cancers (ICD-10 C50) in female 45 and Up Study participants, resident in NSW, were identified from linked NSWCR data for the period 2006-2012. Data not routinely available in the NSWCR, including hormone receptor status, were extracted from the pathology report provided to the registry. RESULTS: Among 143 079 eligible women, 2051 had a first registration of breast cancer following cohort recruitment. The mean age at cancer diagnosis was 64.5 years. Based on cancer registry data, the cancers were predominantly ductal (74.1%), 54.4% were localised to the breast at diagnosis and 24.2% were >50 mm in size. Based on manually extracted data from pathology records, 23.9% of cancers were histological grade 1, 79.6% were oestrogen receptor positive and 71.2% were progestogen receptor positive. These data were mostly complete (<10% missing). HER2 receptor status was less well reported, with 31.9% of cancers having indeterminate or missing data, while 11.3% were reported as positive. Data on lymph node status was missing in 16.1% of breast cancer reports, 33.7% were node positive. 8.0% of breast cancers had involved surgical margins, and this data was missing for 14.1% of cases. CONCLUSION: Pathology information, in addition to that available from routine registry data, is required both for breast cancer research and for monitoring trends in the types of breast cancer occurring over time in Australia. All the important additional data items required are recorded on the pathology report, which is provided to the NSWCR as part of cancer notification but is not routinely coded, and are generally fairly complete. However, access to these data for large-scale studies requires substantial effort. Coding the pathology data and making it routinely available would substantially improve cancer research and enable proper monitoring of breast cancer trends in Australia.

Ethnicity and breast cancer in the UK: Where are we now?

Outcomes from breast cancer for women in the UK have improved significantly over recent decades. These gains are largely attributable to a combination of earlier diagnosis and access to treatments delivered to patients by the National Health Service irrespective of cost. Ethnic minority groups make up almost fifteen percent of the UK population and there is concern however that these groups may have poorer outcomes from the disease. In this short report we seek to summarise what the current evidence tells us about the patterns of breast cancer incidence and outcomes in ethnic minority women in the UK in order to raise awareness about this topic and provide consideration for what future research is needed to address the gaps that may exist.

Ethnicity and the tumour characteristics of invasive breast cancer in over 116,500 women in England.

BACKGROUND: Ethnic minority women are commonly reported to have more aggressive breast cancer than White women, but there is little contemporary national evidence available. METHODS: We analysed data from the National Cancer Registration and Analysis Service on women diagnosed with invasive breast cancer during 2013-2018. Multivariable logistic regression yielded adjusted odds ratios (and 95% confidence intervals) of less favourable tumour characteristics (high stage, high grade, ER negative, Her2 positive) by ethnicity (black African, black Caribbean, Indian, Pakistani and white) in younger (30-46 years) and older (53-70 years) women. RESULTS: In 24,022 women aged 30-46 at diagnosis, all ethnic minority groups apart from Indian women had a significantly greater odds of certain less favourable tumour characteristics compared to white women in fully adjusted models. In 92,555 women aged 53-70, all ethnic minorities had a significantly greater adjusted odds of several of the less favourable tumour characteristics. These differences were most marked in black African and black Caribbean women. CONCLUSIONS: Ethnic minority women are at greater risk of breast cancers with less favourable characteristics, even after allowing for age and other potential confounders. These differences are greater in older than younger women, and in the Black rather than South Asian ethnic groups.

The COVID-19 pandemic and impact on breast cancer diagnoses: what happened in England in the first half of 2020.

Delays in cancer diagnosis and treatment due to the COVID-19 pandemic is a widespread source of concern, but the scale of the challenge for different tumour sites is not known. Routinely collected NHS England Cancer Waiting Time data were analysed to compare activity for breast cancer in the first 6 months of 2020 compared to the same time period in 2019. The number of referrals for suspected breast cancer was 28% lower (N = 231,765 versus N = 322,994), and the number of patients who received their first treatment for a breast cancer diagnosis was 16% lower (N = 19,965 versus N = 23,881). These data suggest that the number of breast cancers diagnosed during the first half of 2020 is not as low as initially feared, and a substantial proportion of the shortfall can be explained by the suspension of routine screening in March 2020. Further work is needed to examine in detail the impact of measures to manage the COVID-19 pandemic on breast cancer outcomes.

Lifelong vegetarianism and breast cancer risk: a large multicentre case control study in India.

BACKGROUND: The lower incidence of breast cancer in Asian populations where the intake of animal products is lower than that of Western populations has led some to suggest that a vegetarian diet might reduce breast cancer risk. METHODS: Between 2011 and 2014 we conducted a multicentre hospital based case-control study in eight cancer centres in India. Eligible cases were women aged 30-70 years, with newly diagnosed invasive breast cancer (ICD10 C50). Controls were frequency matched to the cases by age and region of residence and chosen from the accompanying attendants of the patients with cancer or those patients in the general hospital without cancer. Information about dietary, lifestyle, reproductive and socio-demographic factors were collected using an interviewer administered structured questionnaire. Multivariate logistic regression models were used to estimate the odds ratio (OR) and 95% confidence intervals for the risk of breast cancer in relation to lifelong vegetarianism, adjusting for known risk factors for the disease. RESULTS: The study included 2101 cases and 2255 controls. The mean age at recruitment was similar in cases (49.7 years (SE 9.7)) and controls (49.8 years (SE 9.1)). About a quarter of the population were lifelong vegetarians and the rates varied significantly by region. On multivariate analysis, with adjustment for known risk factors for the disease, the risk of breast cancer was not decreased in lifelong vegetarians (OR 1.09 (95% CI 0.93-1.29)). CONCLUSIONS: Lifelong exposure to a vegetarian diet appears to have little, if any effect on the risk of breast cancer.

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.

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.

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.

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

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.