What the Generations Study is teaching us about breast cancer risk

Breast cancer doesn’t have one single cause. Our genes, hormones, lifestyle and environment can all play a part. Our Generations study is working to understand how these factors work together. Launched in 2004, the study is following more than 110,000 women over 40 years. Some will develop breast cancer, others won’t. Through regular questionnaires, DNA analysis and collection of blood samples, our researchers are building a detailed picture of what influences breast cancer risk. 

Now, 4 recent studies are showing just how powerful that information can be.

Many different things affect your risk of getting breast cancer. Some of these things can’t be changed, but others can.

Using data from the Generations Study, researchers mapped how lifestyle factors linked to breast cancer risk, like smoking and alcohol consumption, change throughout women's lives.

Professor Marc Gunter and PhD Student Isobel Jackson found clear patterns. Alcohol consumption, smoking and physical activity tended to peak in late adolescence. BMI generally increased with age and peaked in the 60s. And some changes happened more rapidly during certain stages of life, particularly mid-adulthood.

This new study also found that patterns differed between generations. Younger women in the study generally had higher BMIs across their lives and earlier peaks in smoking and alcohol consumption compared to older women.

Understanding when these lifestyle behaviours are most likely to change could help public health experts develop more targeted, age-specific approaches to reducing breast cancer risk.

Breast cancer isn’t one disease. Different tumours have different features, which can affect how they behave and how they’re treated.

The paper, published in the Journal of the National Cancer Institute, used data from 24 studies, including the Generations Study. The researchers investigated if certain breast cancer risk factors are more strongly linked with particular tumour features.

 They looked at factors including reproductive history, hormone replacement therapy (HRT), BMI, alcohol consumption, smoking and family history of breast cancer. And compared them with features like whether the tumour was oestrogen receptor (ER) or progesterone receptor (PR) positive, and what grade it was. They uncovered several clear links. Women who hadn’t given birth or went through the menopause later, were more likely to develop ER-positive breast cancer. And current combined HRT use was linked with lower-grade tumours.

BMI was also linked to tumour features in different ways before and after the menopause. In premenopausal women, higher BMI was linked with lower rates of ER- positive tumours and higher-grade tumours. After the menopause, higher BMI was linked with PR-positive and higher-grade tumours.

This study helps researchers not only better understand what affects breast cancer risk, but why different forms of the disease may develop.

Some breast cancers are diagnosed between routine screening appointments. These are called interval breast cancers.

Researchers analysed data from 1,940 women in the Generations Study who developed breast cancer, comparing women whose cancer was detected through screening with those diagnosed between screening rounds.

Earlier research had shown that a lower BMI, hormone therapy (HRT) and family history were linked with a higher risk of interval breast cancer. But these factors are also linked with dense breasts, which increases breast cancer risk and makes them harder to see on mammograms. This study found that having dense breasts and several other risk factors independently affected how likely someone was to get an interval breast cancer.

And that after taking breast density into account, a later menopause, current HRT use, a history of benign breast disease and being underweight at age 20 were associated with a higher likelihood of having an interval cancer.

These findings could help identify who may benefit from more personalised screening in the future, but more research is needed.

At the moment, women under 50 in England are largely referred for specialist breast cancer risk assessment based on their family history. But family history only tells part of the story.

Using data from 1,258 women under 50 in the Generations Study, they found that the current NICE criteria could miss up to 95% of women under 50 who go on to develop breast cancer within ten years.

And with a more comprehensive risk assessment tool called BOADICEA, the researchers identified 8 times as many at-risk women in this age group.

Bu there is a trade-off. Using the full BOADICEA model across all women under 50 would mean many more people being referred for further assessment, with major implications for NHS capacity.

So, the next step is to test how risk assessments like this could be implemented safely, equitably, and cost-effectively in routine care.

Together, these studies show the strength of long-term research like the Breast Cancer Now Generations Study, which is helping us better understand who is most at risk of developing breast cancer and why.

Breast Cancer Now thanks M&S for their generous support of the Breast Cancer Now Generations Study. We would also like to acknowledge the past support of Avon Cosmetics, the Garfield Weston Foundation and Walk the Walk as very generous founding funders.