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New approach could better predict breast cancer risk due to family history

Metastatic breast cancer cells in pleural fluid

Metastatic breast cancer cells in pleural fluid. Image from flickr user euthman. CC-BY 2.0

Scientists funded by Breast Cancer Now and Cancer Research UK have demonstrated a more accurate method to assess a woman’s familial risk of breast cancer, which could one day be added to existing models to help better predict an individual’s overall risk of breast cancer.

In a new analysis of 103,738 women from the Breast Cancer Now Generations Study, published in Breast Cancer Research and Treatment, researchers have shown that the Family History Score (FHS) – applied to breast cancer incidence for the first time – can better determine a woman’s breast cancer risk due to her family history than existing methods, such as assessing the number of relatives diagnosed with breast cancer, the type of relative diagnosed and their age(s) at diagnosis.

The new approach takes into account both the actual number of breast cancer cases in a woman’s first degree relatives and the expected number given the family’s size and age-structure. If validated in further datasets and brought into clinics, this new method could see women being told more accurately of their risk of developing breast cancer, leading them to make more informed decisions about managing and reducing their risk.

Family history is an important breast cancer risk factor, and one that can cause considerable anxiety to women. About 10% of breast cancers are related to family history, and women with a family history are more likely to develop breast cancer and at a younger age.

GPs are able to refer those deemed to have an increased risk of breast cancer to a genetics clinic or family history clinic for specialist care, where advice and support is offered to help both reduce the risk of breast cancer developing and make sure the disease is spotted early if it does occur.

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Predicting risk more precisely

In new research, scientists at The Institute of Cancer Research, London demonstrated that assessing family history not only by cases in the family but also in the context of their family size and age structure can offer a more accurate prediction of risk. For example, someone with many older women in her family would be expected to have more breast cancers in her family than a woman with a smaller, younger family, which needs to be taken into account.

The new method also provides a more precise risk figure by giving a score on a continuum, rather than in two or three categories of risk, and could potentially be incorporated into wider risk prediction models for breast cancer to predict risk more precisely.

The approach was tested using the Breast Cancer Now Generations Study – one of the world’s largest prospective cohort studies into the causes of breast cancer, which is following more than 113,000 UK women for a period of 40 years – which collected extensive detail from its participants about their family structure.

'Important to make better predictions of risk'

Crucially, the researchers – led by Professor Anthony Swerdlow and Hannah Brewer at the ICR – found that women with the highest Family History Scores were 3.5 times more likely to develop breast cancer than those with no first degree family history of the disease.

With existing methods showing that those at the highest risk are up to 2.5 times more likely to develop breast cancer than those with no family history of breast cancer, the FHS method is able to identify a group at an even higher risk than other methods of categorising relatives with the disease. 

Furthermore, the researchers then combined FHS with a number of other family variables, including the type and number of relatives with breast cancer, and compared the fit of these models with the true distribution of the Generations Study data. These results suggest that FHS combined with the age of the youngest relative at their breast cancer diagnosis could be an even more precise method.

Study leader Anthony Swerdlow, Professor of Epidemiology at The Institute of Cancer Research, London, said: “Our study has demonstrated a way to estimate women’s familial risk of developing breast cancer that is more precise than conventionally used family history measures. This Family History Score takes into account the size and structure of a woman’s family, and compares the number of breast cancer cases that occurred in her family with the number expected in the general population.

“Improving the way we measure familial risk of breast cancer is important to help make better predictions about individual women’s risk, in order to offer women better advice on the implications of their family history for themselves and their relatives.”

 'A really important finding'

Baroness Delyth Morgan, Chief Executive at Breast Cancer Now, which helped fund the study, said: “That this new approach could more precisely bring to light an individuals’ familial risk of breast cancer is a really important finding.

“Having an increased risk of breast cancer due to a family history can understandably cause considerable anxiety, and the ability to assess this increase with even greater accuracy will now be fundamental in helping women make informed choices to manage their risk.

“If validated in further studies, we hope this crucial method could be added to existing risk models to empower women to take the best risk-reducing action for them.

“While most breast cancers are not linked to a family history, in around one in ten cases a family history will have been a contributing factor and it remains an important risk factor for the disease. If anyone is concerned that they may have an increased risk of breast cancer due to their family history, we’d highly encourage you to speak to your GP.”

Helping women make informed decisions

Professor Arnie Purushotham, Cancer Research UK’s senior clinical adviser, said: “This important study reveals a more precise way to predict a woman’s chances of developing breast cancer if she has a family history of the disease. Although rare, having a high risk of breast cancer because of family history can have huge implications for women, so being able to accurately understand this risk is absolutely essential. This new approach could help women, with their doctors, make informed decisions on whether to take preventative action against breast cancer.”

With more women being diagnosed with breast cancer than ever before, the Breast Cancer Now Generations Study – which is based at The Institute of Cancer Research, London – continues to investigate the genetic, lifestyle and environmental factors that may change a woman’s risk of developing breast cancer.

The Study has already led to a number of significant discoveries into the interlinked causes of breast cancer, including clarifying that women taking combined HRT are 2.7 times more likely to develop breast cancer than non-users.



Anthony Swerdlow breast cancer Breast Cancer Now generations study
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