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Breast Cancer

Commonest cancer among UK women

1 in 8 UK women diagnosed during their lifetime

woman having a mammogram

Breast cancer is the most common cancer in women worldwide and its incidence is increasing. The Cancer Epidemiology Unit has a long-established and substantial programme of research aimed at improving our understanding of the aetiology of the disease, and informing public health policy on breast cancer prevention. The unit hosts two ongoing international collaborations in breast cancer: The Collaborative Group on Hormonal Factors in Breast Cancer, which has published landmark reports on breast cancer risk in relation to a wide range of lifestyle and familial risk factors, including oral contraceptive use (2019, 2012, 2004, 2002, 2001, 1997, 1996), and the Endogenous Hormones and Breast Cancer Collaborative Group, which has yielded important findings on the role of sex hormones and IGF on breast cancer risk (Tin Tin et al, 2021; Key et al, 2010; Key et al, 2003). Our work on breast cancer risk in relation to use of hormone replacement therapy (HRT) within The Million Women Study has provided reliable evidence regarding the increased risks associated with specific patterns of HRT use which have changed clinical practice (Beral et al 2011 and 2003, Reeves et al 2006). The Million Women Study is also a rich source of information on the role of other modifiable risk factors in the development of breast cancer such as alcohol consumption (Allen et al, 2009; Floud et al, 2023), adiposity (Reeves et al, 2007) and childbearing (Collaborative Group on Hormonal Factors in Breast Cancer, 2002).

To date, bloods from around 16,000 Million Women Study participants with breast cancer, and a similar number of women without breast cancer, have been collected and processed in order to examine the role of genetic risk factors in the development of the disease. Analyses of information on a limited number of breast cancer susceptibility loci in around 10,000 of these breast cancer cases and a similar number of controls provided the first substantive published results on gene-environment interactions for breast cancer, showing that risks associated with most known susceptibility loci do not vary by other established environmental risk factors (Travis et al, 2010). The study was also among the first to report on the predictive value of a polygenic risk score for breast cancer showing that such a score was more predictive for hormone sensitive disease (Reeves et al, 2010). We have recently obtained genotyping array and exome-sequencing data on those participants who provided a blood sample and these data are being used to generate new information about the relationship between how and why a woman’s genetic make-up influences her risk of developing breast cancer.

Breast cancer is known to be a heterogeneous disease and there is increasing interest in examining risk factors for relevant subtypes of breast cancer. The Million Women Study has already reported on risk factors for breast cancer subtypes defined by their invasiveness (Reeves et al, 2012), hormone receptor status (Collaborative Group on Hormonal Factors in Breast Cancer, 2012) and histological type (Reeves et al, 2006; Reeves et al, 2009) and we have just completed work to explore risk factors, separately, for the main molecular subtypes of breast cancer that have been associated with clinical outcome. Linkage of the cohort to NHS databases, including the Cancer Outcomes and Services Dataset and Hospital Episodes Statistics, has substantially broadened the scope of questions that can be addressed within the study and future work will consider adverse outcomes following diagnosis and treatment for breast cancer, as well as factors affecting survival.

In analyses aimed at investigating factors which influence the likelihood of having a breast cancer detected at routine screening, we have shown that recent users of menopausal hormone therapy are less likely to have their breast cancer detected at screening, and more likely to have it diagnosed in the interval between screens (Banks et al, 2004). We have also shown that women with low BMI, a first-degree family history of breast cancer and women with previous surgery for benign breast disease, may also experience some reduction in mammographic screening sensitivity (Barnes et al, 2024).

In collaboration with the NHS Breast Screening Programme, the unit designed the Breast Screening Age Extension Trial (AgeX Trial), which is the largest ever randomised trial to date. The unit acts as co-ordinating centre for the trial which randomised four million women to assess the net effects of offering additional breast cancer screening before age 50 and after age 70. The results of the trial should provide much needed information about the risks and benefits of extending routine breast screening to a wider age-group.

Our team

Selected publications