Manchester researchers identify system that can detect more breast cancer patients eligible for testing for cancer risk genes

Researchers have shown that their system, developed at Manchester University NHS Foundation Trust (MFT), can identify more breast cancer patients who are eligible for testing for inherited faulty genes that can cause breast cancer. This could help to improve detection rates of people at an increased risk of developing breast cancer.

The study, which was funded by the National Institute for Health and Care Research (NIHR) Manchester Biomedical Research Centre (BRC), of more than 1,000 DNA samples from women at MFT showed a simple system, called the Manchester Score, can detect more women with breast cancer who have a faulty gene that causes the disease.

Using this system also means fewer women with breast cancer would require genetic testing, as it was shown to be more sensitive and specific than current testing criteria.

Breast cancer, the most common type of cancer in the UK, can be strongly influenced by genes and can run in families. Humans carry certain genes that are normally protective against cancer. These genes correct any DNA damage that naturally happens when cells divide.

Inheriting faulty versions or variants of these genes significantly raises the risk of developing cancer, because the altered genes cannot repair the damaged cells, which can build up and form a tumour.

In this study, researchers tested all participants for the three most important genes – BRCA1, BRCA2 and PALB2 – which raise breast cancer risk if they become altered.

Current NHS genetic testing criteria was updated in April 2022 to make it more widely available for women with breast cancer. The criteria includes all women diagnosed under 40 years old except those with grade 1 breast cancer, where cancer cells are not growing rapidly.

Researchers compared these guidelines to different thresholds of the Manchester Scoring system – a points score used to assess the likelihood of a breast cancer genetic fault being present in a family. To calculate a score, clinicians review family history, type of cancer, age at diagnosis and tumour characteristics.

A Manchester Score of 15-19 points equates to a 10 per cent likelihood of a genetic fault, while a score of 20-24 points shows a 20 per cent likelihood. A score of more than 40 points is equivalent to at least a 75 per cent likelihood. The 15 points threshold for genetic testing is used in current NHS criteria.

The study was led by Professor Gareth Evans, Consultant in Medical Genetics and Cancer Epidemiology at MFT, who developed the Manchester Score. Published in Genetics in Medicine, it was a collaboration between researchers from MFT, The Institute of Cancer Research, London, NIHR Royal Marsden BRC and Brighton and Sussex Clinical Trials Unit.

Patient DNA samples were drawn from three sources – women diagnosed with breast cancer at MFT who met NHS testing criteria, and those who took part in the BRCA-DIRECT and Predicting Risk Of Cancer At Screening (PROCAS) studies in North West England.

Among the 1,061 DNA samples, 36 women were shown to have a genetic fault which raises breast cancer risk. Researchers found current NHS testing criteria identified 21 of these women.

A better detection rate was found using a lower Manchester Score threshold of 12 points, which identified 24 women. However, researchers found that by loosening the threshold to a Manchester Score of three points or higher, this detected all 36 women with genetic faults even if their likelihood of having a fault was very low.

No genetic faults were found in 158 women with non-aggressive grade 1 cancers.

Professor Gareth Evans, who is also NIHR Manchester BRC Cancer Prevention and Early Detection Theme Lead and Professor in Medical Genetics and Cancer Epidemiology at The University of Manchester, said: “Our study has shown the Manchester Scoring system, while simplistic, can detect more women who have genetic faults which can cause breast cancer than current testing criteria, while testing less women.

“If we can improve risk prediction and early detection of breast cancer, then we can give people the best chance of surviving the disease, and for their relatives reducing their risk of developing it or even avoiding it altogether.”