Over the past two decades, 110,000 women of all ages, from right across the UK, have completed half a million questionnaires and provided thousands upon thousands of blood samples. Between them, their efforts have helped create an unmatched bank of data, enabling groundbreaking research into the causes of a disease that affects 55,000 women in the UK every year.
Now in its 20th year, the Breast Cancer Now Generations Study is one of the world’s largest and longest-running studies into the causes of breast cancer.
Led by the Institute of Cancer Research, London, and funded by Breast Cancer Now, it has contributed to the discovery of hundreds of genetic changes linked to breast cancer and shed light on the major lifestyle and hormonal factors associated with the disease. It’s hoped it will allow doctors to predict which women are at high risk, paving the way for preventative and early detection strategies that will save millions of lives.
“We know that there is never one single cause of breast cancer,” says Professor Amy Berrington who, along with Professor Montserrat Garcia-Closas, is leading the study. “A combination of genes, lifestyle choices and events throughout our lives all contribute to the chances of developing the disease.
“This study has uncovered risk factors that, when combined, can help to identify women who have a high chance of developing breast cancer in the future.
“And it could help them access more targeted advice about reducing their risk through preventative surgeries, more frequent screening and risk-reducing drugs.”
“The study is set to run for another 20 years to continue expanding knowledge about the disease and developing better risk assessment tools, so that we can prevent more breast cancer cases and ensure women receive more personalised and effective care.”
Here the study leads explain some of the major risk factors uncovered by their research that influence your chances of developing breast cancer.
Genetic changes
“In recent years there has been enormous progress in worldwide research to find the genetic changes that increase the risk of breast cancer,” says Professor Berrington.
“The samples contributed to the Generations Study have been an important part of this international effort.
“Over 300 genetic changes called single nucleotide polymorphisms (SNPs) have now been discovered that affect the risk of breast cancer. Each SNP on its own has a small effect, but when combined the impact is considerable.
“These discoveries have been used to help develop a genetic risk score that can help to identify high-risk women, even if they do not have relatives with cancer.”
Family history
“One in 10 cases of breast cancer occurs in a woman whose mother, sister or daughter has already had the disease,” says Professor Garcia-Closas.
“However, when predicting someone’s risk, researchers didn’t just consider the number of cases in a woman’s family. The size of family matters too. Women with many sisters might be expected, on average, to have a sister with breast cancer more often than women with only one sister.”
Similarly, the younger the relatives are, the less likely, on average, that they will have had breast cancer. “The study’s researchers developed a more accurate method to assess family history risks, considering both the number of breast cancer cases in a woman’s first-degree relatives, and the number and age of her female relatives. This new method offers women a more accurate prediction of their risk of breast cancer, allowing them to make more informed decisions.”
An early first period
“The age at which a girl has her first period impacts her chances of developing breast cancer later in life,” says Professor Berrington. “This might be because women who menstruate earlier are exposed to female sex hormones for a longer period of time.
“Women born in the 1940s had their first period about a year younger than those born at the beginning of that century. Although there was little change between most generations born after the Second World War, the average age for a first period decreased again for women born in the late 1980s and early 1990s.
“Other factors that influence the age at which a woman first menstruates include being overweight as a child and being physically inactive.
“The study also found that mothers who smoked or had pre-eclampsia during pregnancy were more likely to have daughters who started their period early.”
Smoking in your teens Smoking is known to increase the risk of 14 different types of cancer, most notably lung cancer. But until recently, it has been uncertain whether the same could apply, to a lesser extent, to breast cancer.
“Researchers analysed information provided by the Breast Cancer Now Generations Study participants and found that those who had smoked at some point in their life had a 14 per cent greater chance of developing breast cancer than women who had never smoked,” says Professor Garcia-Closas.
“This risk was even greater – by 24 per cent – for women who had started smoking before 17.
“These risks may particularly apply to women already at an increased risk of breast cancer due to their family history of the disease.
“Results showed that female smokers with a family history of breast cancer were around 35 per cent more likely to develop the disease than a woman with a family history who had never smoked.”
Being inactive
Taking part in more physical activity can lower the risk of breast cancer both before and after menopause. “Physical activity means any type of movement that uses energy,” says Professor Berrington.
“Exercise is one type, but others include gardening, swimming and housework. Data collected from over half a million younger women from 19 different studies around the world, including the Generations Study, showed that higher levels of leisure time physical activity were associated with a modest decrease in risk of breast cancer in young women.
“This was seen across the whole range of activity levels studied. This means that any type of exercise, whether you are very active or not, is likely to be good for you.”
Being childless
Pregnancy and childbirth reduce the risk of breast cancer in the long term. “The study found that 10 years after having a baby, women are less likely to get breast cancer compared to those who never had a baby,” says Professor Garcia-Closas. “However, although it is rare to have cancer soon after having a baby, the risk for having an aggressive cancer type (triple-negative) is slightly increased.
“Overall, in the long term, pregnancy reduces the risk of the disease for most women – but having children can affect a woman’s risk in different ways.”
High levels of fertility hormones
High levels of anti-Müllerian hormone (AMH) before the menopause – a hormone that indicates the size of a woman’s ovarian reserve – is associated with an increased risk of breast cancer.
“Scientists from the NYU School of Medicine analysed blood samples from participants of 10 cohort studies – including the Breast Cancer Now Generations Study – to examine the association of AMH levels with breast cancer risk,” explains Professor Berrington.
“Those with higher AMH levels for their age tend to reach menopause later in life, which is itself known to be a risk factor for breast cancer – but the study found that AMH levels predict breast cancer risk even for breast cancer that occurs before menopause.
Earlier menopause
The age a woman reaches menopause has long been established as a risk factor for breast cancer. On average, breast cancer risk increases after menopause. This is true both for natural menopause and artificial menopause, which occurs after surgery, for example.
“Our researchers and collaborators found several genes and other genetic changes that can influence the chances of having an early menopause,” says Professor Garcia-Closas. “It is known that there is a link between the menopausal age of mothers and daughters, but lifestyle factors also have an impact.
“Menopause occurs at a younger age in smokers, but drinking alcohol, being heavier and gaining weight as an adult are factors associated with later menopause, so these are lifestyle risk factors that women need to be informed about.”
To find out more about the Generations Study you can visit icr.ac.uk/generations. Discover the work of Breast Cancer Now at breastcancernow.org
