'Risk Determination and Prevention of Breast Cancer',  published today in the journal Breast Cancer Research, identifies the critical gaps that must be addressed if we are to reverse the increase in breast cancer expected over the next 10 years - and reach a tipping point where more breast cancers will be prevented in the general population, not only in women at high risk. High breast density is highlighted as a significant risk factor for breast cancer that could play a key role in redefining the risk of breast cancer faced by each individual woman.
The number of people diagnosed with breast cancer in the UK is on the rise and this trend is projected to continue until at least 2030. The increase is partly due to an ageing population, insufficient levels of physical activity, increases in obesity and alcohol consumption, women having fewer children and having them later in life, all of which are risk factors for the disease.
The four key risk and prevention gaps identified in 'Risk Determination and Prevention of Breast Cancer' are:
- Risk estimation: accurate ways to estimate risk in the general population and in women at high risk. Adding information about breast density and newly identified genes is likely to improve existing models.
- Preventive therapy: ways to predict which women will benefit from current preventive therapies and new approaches for those who do not benefit from current preventive treatments.
- Lifestyle: identification of the most effective and acceptable routes for supporting women to achieve healthy ways of life, in relation to weight control, alcohol and physical activity to reduce their breast cancer risk.
- Biology of risk: a clear understanding of the biological mechanisms behind additional factors that influence breast cancer risk, including an early first pregnancy and restricting energy intake, to help find treatments which mimic their risk-reducing effects.
Current risk estimation models are based on breast cancer incidence in the family and hormonal factors such as age of first pregnancy and use of hormone replacement therapy (HRT), as lead author Professor Anthony Howell, Director of Research at Genesis Breast Cancer Prevention, based at the University Hospital of South Manchester, explains:
“With current breast cancer risk models we know we can predict fairly accurately that 10% of women in the population are at high or moderate risk of the disease. We also know that using currently available drugs up to half of breast cancers can be prevented in these women.
"However, there is a major gap in how we identify women at high risk who could benefit from preventive therapy. Additionally, there is a gap in determining how much the risk assessment would be improved by adding additional information about other risk factors, such as breast density, and the results of gene tests."
Breast density as a risk factor
Over 700,000 women in the UK of breast screening age are estimated to be at higher than average risk of developing breast cancer due to having a high breast density, which can also mask the signs of a tumour on a mammogram. Other countries - the United States and Canada - have already taken significant steps to inform women about the implications of having high breast density.
Baroness Delyth Morgan, Chief Executive at Breast Cancer Campaign, says:
"The best weapon in overcoming breast cancer is the ability to stop the disease occurring in the first place. To do this, we need better ways to identify who is most at risk. The emerging evidence on risk factors such as breast density, which we now know is putting hundreds of thousands of women at risk of developing breast cancer, must be taken into consideration and more must be done."
Breast density refers to the amount of collagen and glandular tissue compared with fat in the breast. This can be estimated on mammograms - high density occurring when there is more collagen and glandular tissue than fat in the breast.
High breast density is a significant risk factor for breast cancer: women with the highest density are up to five times more likely to develop breast cancer than women with low density , and twice as likely to develop the disease compared to women with average breast density.
The exact cause of the association is yet to be discovered, but past research funded by Breast Cancer Campaign has found a link between a high calorie diet and high breast density later in life , as well as finding that women with high breast density are 25.5 times more likely for their tumour to be located in the area of highest density than in the area of lowest density - and that these areas of higher density could be seen on mammograms up to 5 years before diagnosis .
Many more women currently not thought to be at high risk of breast cancer could qualify for risk-reducing options if information about their breast density was used to help determine their risk of developing the disease. A survey carried out by ICM on behalf of Breast Cancer Campaign in response to the findings of ‘Risk Determination and Prevention of Breast Cancer’, revealed that 84% of women aged 45+ would want advice on how to reduce their risk if they were found to have high breast density .
Preventive therapy and breast density
Currently, the only proven way to reduce breast density is by using chemoprevention drugs, and this reduction in density leads to an associated reduction in risk. Breast Cancer Campaign’s survey found that 34% of women would be willing to consider taking risk-reducing drugs should they qualify. Scientists also believe information about breast density could be used to predict if a woman will benefit from chemoprevention.
However, 'Risk Determination and Prevention of Breast Cancer' highlights the need to identify women at high risk who could be offered risk-reducing treatments, and the women who would most benefit from the drugs. Chemoprevention drugs are currently effective in up to half of women, and it is essential to find ways to predict whether a woman would benefit from taking them or not, as well as developing more effective risk-reducing treatments.
To accelerate progress in this area of research, Breast Cancer Campaign has just commissioned research worth around £1 million to explore how monitoring a woman’s breast density can help determine if she will benefit from risk-reducing treatment, in addition to research testing a new type of chemoprevention drug.
The future – what needs to be done?
A UK clinical trial is taking place to test the feasibility of assessing breast density at routine screening appointments, incorporating this information into risk models and adapting screening intervals based on risk .
In addition, Breast Cancer Campaign-funded scientist Dr Susan Astley is using images taken with ‘digital breast tomosynthesis’, a new type of ‘3D mammography’, to develop better ways of measuring areas of high density during screening*. Taking current progress into account, Breast Cancer Campaign hopes that a pilot looking at incorporating information about breast density into the NHS Breast Screening Programme could begin in 3 – 5 years.
The Breast Cancer Campaign survey, which aimed to gauge the public’s attitude towards breast density information and breast cancer risk and prevention, revealed that 83% of women aged 45 or over agree that more should be done to inform women about how breast density impacts on their risk, 81% in the same age group would want to be informed if they were found to have high breast density following a screening appointment, and 84% said they would want advice on how to reduce their risk if they were found to have high breast density.
Until more evidence is collected about how information about breast density could be used to calculate risk, the best way for women to manage their breast cancer risk is through following recommended lifestyle advice, and being aware of the signs and symptoms of breast cancer so they can report any unusual changes to their GP. 'Risk Determination and Prevention of Breast Cancer' highlights evidence that shows lifestyle adjustments can reduce a woman’s breast cancer risk by around 30%.
These lifestyle adjustments include:
- Achieve and maintain a healthy weight: Breast Cancer Campaign’s survey revealed 81% of females aged 18+ would be willing to do this to lower their risk.
- Exercise: women should aim to be physically active at moderate intensities (equivalent to brisk walking) for around 30 minutes, 5 times per week: the Breast Cancer Campaign survey revealed 69% of women aged 18+ would be willing to do this to lower their risk.
- Reduce alcohol intake: consuming 21 units per week (a unit being a small glass of wine or half a pint of beer) increases breast cancer risk by 40% compared to drinking no alcohol, therefore women should limit alcohol intake to no more than 5 units per week to lower their risk of breast cancer: Breast Cancer Campaign’s survey 66% of females aged 18+ said they would be willing to do this to lower their risk.
Even without high risk identification, all women stand to benefit from supportive ways to manage body weight, become more physically active and limiting alcohol intake.
Baroness Delyth Morgan, Chief Executive at Breast Cancer Campaign, says:
“Our 2013 Gap Analysis highlighted what steps must be taken to overcome breast cancer by 2050. It is becoming clear, as more and more research emerges, that we can make that goal a reality, but everyone must play their part for this to happen. We therefore call on Public Health England to work with the breast cancer community to develop a breast cancer risk and prevention action plan, to ensure we cut breast cancer incidence across the country.
"Many women are unaware of the key risk factors for breast cancer, many of which are out of their control, and it is so important that women know what they can do to manage their risk. Until progress is made on a scientific and clinical level that enables women to be informed about breast density, it remains even more vital that women are aware of the signs and symptoms of breast cancer to look out for and follow the recommended lifestyle advice to lower their risk.
"We have just invested around £1m in research specifically aiming to tackle gaps in the prevention of breast cancer, and we need to raise at least £8.5million over the next decade to accelerate research in this area. This would give us a much greater understanding of the risk of breast cancer each woman faces and help us reach our goal that by 2025, up to 20% of breast cancers will be prevented."
Professor Howell says:
"This is a crucial time for us to examine the gaps in research concerning breast cancer risk and prevention, as more and more women are diagnosed with the disease. Our team of experts feel that a two-pronged attack – implementing what we know works, such as preventive therapy and lifestyle advice, as well as researching how we can develop new approaches to prevent the disease – could lead to significant progress over the next 10 years, with many more cases of breast cancer prevented.
"Risk Determination and Prevention of Breast Cancer, facilitated by Breast Cancer Campaign and published as an open access review in the journal Breast Cancer Research on Monday 29 September, follows on from Breast Cancer Campaign’s 2013 Gap Analysis, which highlighted the key gaps in eight areas of breast cancer research that must be addressed in order to overcome breast cancer by 2050."
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 Howell A, Anderson AS, Clarke RB, Duffy SW, Evans DG, Garcia-Closas M, Gescher AJ, Key TJ, Saxton JM, Harvie MN. Risk determination and prevention of breast cancer. Breast Cancer Research 2014, 16:446.
 McCormack VA, dos Santos SI. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2006, 15:1159–1169.
 Mishra, GD et al. Energy intake and dietary patterns in childhood and throughout adulthood and mammographic density: results from a British prospective cohort. Cancer Causes & Control 2011, 22(2): 227–235.
 Pinto Pereira, SM et al. Localized fibroglandular tissue as a predictor of future tumour location within the breast. Cancer Epidemiol Biomarkers Prev 2011. 20; 1718.
 ICM interviewed a random sample of 2,048 adults aged 18+ in Great Britain online between 5th and 7th September 2014. Surveys were conducted across the country and the results have been weighted to the profile of all adults. ICM is a member of the British Polling Council and abides by its rules.
 Evans DG. et al. Assessing Individual Breast Cancer Risk within the U.K. National Health Service Breast Screening Program: A New Paradigm for Cancer Prevention. Cancer Prev Res 2012, 5; 943.