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Understanding breast cancer risk in Chinese populations

Obesity has long been associated with an increased risk of breast cancer in post-menopausal women. But the relationship between obesity and breast cancer is less clear in pre-menopausal women. Moreover, a lot of uncertainty remains around the associations between body weight and breast cancer in countries such as China, where the average BMI is lower than in western countries, along with differences in the prevalence of other risk factors between western and eastern cultures. There is a need to better understand how morphological and lifestyle differences between populations may influence cancer incidence, in order to better understand and identify who is at an increased risk.

An upcoming study from the Clinical Trial Service & Epidemiological Studies Unit (CTSU) at the Nuffield Department of Population Health, led by Dr Christiana Kartsonaki and Dr Ling Yang, is investigating breast cancer incidence in Chinese populations in relation to adiposity measures such as BMI, waist circumference and body fat percentage.

The team used data from the China Kadoorie Biobank, a cohort study that has collected information from over half a million individuals from China since 2004. During an average of 10 years of follow-up of this cohort, there were 2,053 cases of breast cancer, which allows the team to assess what demographic or lifestyle factors might be influencing risk in Chinese women.

Early results suggest that, like western populations, increased levels of adipose tissue leading to higher BMIs are associated with higher risks of breast cancer in Chinese women, particularly among post-menopausal women. These results highlight the importance of understanding relative cancer risk factors between different ethnicities. Whilst some factors such as obesity are often common causes of cancer across all populations, there are many key biological and lifestyle factors that differ between western and eastern populations. Understanding how these may impact cancer risk in different ways will allow researchers to inform policy, so that clinicians may better identify who may have a higher risk of developing cancer.

About the CTSU

The Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) aims to generate and disseminate reliable evidence from observational epidemiology and from randomised trials that leads to practicable methods of avoiding premature death and disability.

This project is being led by Dr Christiana Kartsonaki and Dr Ling Yang in conjunction with Prof. Zhengming Chen.

New hydrogel technology has promise in breast cancer modelling

In science, a model is used as a representation of something in the real world, so that ideas and concepts may be tested out. Models have a variety uses, but in cancer biology they are often popular as they can help to mimic the complex environment seen in human   disease. Models are used to explore the effects of new drugs, understand genetic or cellular pathways on tumour development or predict the potential response of a patients cancer.

It’s in a researcher’s best interest to create a model that is as faithful to the real world as possible, so that the outcomes are accurate and can translate successfully into humans. However, the go-to models to recapitulate human cells in a lab use, a protein matrix extracted from mouse tumours, which is used to resemble the extracellular environment found human tumours. But the extent to which mouse matrix can be used is limited by its fixed extracellular matrix components, which are often not representative of the human tissue, and the inability to add or remove the individual extracellular components to explore the influence these on tumour growth.

Dr Gillian Farnie, Nuffield Department of Orthopaedics, Rheumatology and Musculorskeletal Sciences, has focused her work on developing new models that allow human breast cancer cells to be grown and researched, whilst overcoming these limitations.

A recent publication in Matrix Biology, funded by the NC3Rs, outlines a new peptide hydrogel developed by the Farnie group in collaboration with Prof Merry (University of Nottingham).  This new peptide hydrogel offers the added benefit of being customisable, by incorporating or removing specific extracellular matrix components that researchers want to test, to better understand their influence on cancer cells. It therefore allows full control over the biochemical and physical properties of the model, providing researchers with the opportunity to more accurately adapt the model to the real-life environment of human breast tumour.

The new technology’s applications are incredibly widespread and promising. For example, certain extracellular matrix proteins, when found in high quantities in a tumour, can often be associated with a poorer prognosis for a patient. Researchers may want to understand if this is a simple correlation, or if the proteins are assisting the cancer in some way, such as promoting treatment resistance. The ability to remove these proteins from a cancer model and test the response, whilst remaining faithful and accurate to human cells, is incredibly useful and can allow us to discover therapeutic targets.

Dr Gillian Farnie is currently working with the breast cancer research community to apply this new technology in multiple breast tumour research projects. The hydrogel’s applications are not limited to just matrix biology, but also in investigating areas such as the biological significance of blood vessel supply to tumours or even other cancer types outside the breast.

This new hydrogel provides an opportunity to better understand the individual influences of the extracellular matrix, mechanical properties and cell-cell interactions on breast cancer and other disease. It is an open and reproducible model that Dr Farnie is currently publishing a detailed methodology in JOVE, so that more cancer researchers can have access to the new technology.

About this research

Dr Gillian Farnie is based in the Botnar Research Centre, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences.  Her research focuses on the development of patient derived pre-clinical breast cancer models that are used to examine mechanisms of inherent and induced therapy resistance, interrogating both intra-tumour heterogeneity (cancer stem cells) and the tumour microenvironment (ECM, Stroma, Immune cells).

Using big data in breast cancer research

Breast cancer is the most common type of cancer found in the UK population, with 1 in 8 women diagnosed during their lifetime. As a prevalent cancer, it’s important to understand more about the potential causes and relative risks that individuals from different demographics might have.

The Cancer Epidemiology Unit (CEU) at the Nuffield Department of Population Health specialises in large-scale studies into the lifestyle and genetic risk factors of cancers such as breast cancer. In doing so, these studies can provide evidence to inform public health policies and answer outstanding questions about how cancers may arise.

The cause of breast cancer has long been researched and over the last two decades, findings from the Unit’s large prospective studies and international collaborations have helped clarify the role of many risk factors for the disease, including use of menopausal hormones and oral contraceptives, as well as factors relating to childbearing. Within the last year, an updated review of the worldwide evidence carried out in CEU showed that menopausal hormone usage increases the long term risk of breast cancer by almost twice as much as was previously thought, findings which influenced public health guidance. Other recent work found evidence to suggest that high fruit and fibre intake and physical activity may be associated with lower risks of breast cancer.

The CEU work with big data, such as its Million Women Study which contains data from 1.3 million UK women, collected since it began  in 1996. The study includes 1 in 4 of all UK women born between 1935 and 1950 and remains the largest data set of its kind. The study, which aims to resurvey women every 3-5 years, continues to collect information on new potential risk factors such as working night-shifts (which in this case was shown to have no influence on breast cancer incidence).

Enhancing the quality and quantity of the Million Women Study dataset is high on the CEU’s agenda. One area of research where the study hopes to be able to contribute substantially over the next few years is in risk stratification for breast cancer. Prediction models which can be used to assess an individual’s breast cancer risk are key for planning risk-based screening approaches that are tailored to an individual, so refining their accuracy is important to ensure that interventions can be targeted appropriately. However, while existing risk prediction models look promising they need further improvement in their ability to identify those women who are most likely to get breast cancer before they can be applied at a population level. In particular, models should ideally incorporate the whole spectrum of breast cancer risk factors including genetic variation and radiological imaging data.

This will be the next stage for the Million Women Study, as Prof Gill Reeves, Head of the CEU, hopes to integrate new datasets into the study. This includes digital screening images from mammograms, and other clinical information, which could be used in combination with existing information held on participants, to allow the CEU to develop more accurate risk prediction models from the Million Women’s Study.

Prof Gill Reeves, Head of the CEU, says:

“Enriching the quality of datasets such as the Million Women Study will allow us to continue to provide reliable evidence regarding the effects of behavioural and biological factors on breast cancer risk, and help identify women who are at particularly high risk of the disease. In doing so, we can better inform public health advice, and clinical practice.”

To read more about the CEU’s work on breast cancer go to the  CEU website.

About the CEU

The CEU runs the Million Women’s Study (MWS) and EPIC-Oxford (two large cohort studies). Recent grant funding from CRUK has allowed for further enhancement of the MWS so that new clinical data and other potential risk factors for cancer may be integrated.

Prof Gill Reeves, Head of the CEU, is a Professor of Statistical Epidemiology. Her main research interests are the roles of hormonal and other risk factors in the development of female cancers.  She is particularly interested in risk factors and patterns of survival for molecular subtypes of breast cancer.

 

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Study sheds light on risks of breast cancer after pre-invasive disease

Women who are diagnosed with ductal carcinoma in situ (DCIS) during breast screening go on to experience higher risks of developing breast cancer and of death from breast cancer, compared with the general population, according to new research published by The BMJ today. The risks were more than double those of the general population, even for women diagnosed with low or intermediate grade DCIS, and lasted until at least 20 years after diagnosis.

DCIS is a disease where malignant breast cells are found but have not spread beyond the milk ducts.

Diagnoses of DCIS have increased substantially in recent years, especially among women attending breast screening programmes. DCIS isn’t immediately life-threatening and does usually have a good prognosis, but it can increase the risk of developing an invasive breast cancer later on. The extent of this extra risk is uncertain.

So, researchers at the Nuffield Department of Population Health and Public Health England set out to evaluate the long term risks of invasive breast cancer and of death from breast cancer after DCIS diagnosed through breast screening.

Their findings are based on data from 35,024 women in England diagnosed as having DCIS by the NHS Breast Screening Programme from its start in 1988 until March 2014. They compared rates of invasive breast cancer and of death from breast cancer with the corresponding national rates for women of the same age in the same calendar year.

The researchers found that by December 2014, 2,076 women had developed invasive breast cancer, an incidence rate of 8.82 per 1,000 per year and more than double the number expected from national rates. In the same group of women, 310 died from breast cancer, a death rate of 1.26 per 1,000 per year and 70% more than expected from national rates.

For both invasive breast cancer and death from breast cancer, the increases continued for at least two decades.

The results also suggest that women who had more intensive treatment, such as a mastectomy, had a lower long term risk of invasive breast cancer than those who had breast conserving surgery, even when radiotherapy was given.

Professor Sarah Darby from the Nuffield Department of Population Health, who led the research, said ‘This is the first time we have been able to show that women with DCIS have more than double the risk of developing invasive breast cancer and dying from the disease, even up to 20 years after being diagnosed.

‘While this is concerning, understanding more about this risk puts us in a better position to make informed decisions about how to treat and monitor women with DCIS to give them the best possible care and save lives.’

The researchers point out that, at the moment, surveillance of women after a diagnosis of DCIS focuses just on the first few years. In the UK, for example, most women are recalled for yearly surveillance mammograms for five years, after which further follow-up is every three years via the national screening programme up to age 70 years.

Further studies are needed to build on these findings, in particular to try to work out which type of DCIS is most closely linked to the development of invasive breast cancer. This may have implications for follow-up and the frequency of surveillance imaging.

Funding was provided by Cancer Research UK, the National Institute for Health Research Oxford Biomedical Research Centre, and the UK Medical Research Council.

Breast cancer awareness month