Faulty gene increases breast cancer risk to ‘one in three’

In collaboration with the Press Association
A breast cancer cell

An international team of scientists has revealed by how much a rare inherited faulty gene increases a woman’s chances of developing breast cancer.

"It's another piece of information to help women make proper informed choices about how they may help to minimise their own risk" - Professor Peter Johnson, Cancer Research UK

The study, led by the University of Cambridge and part-funded by Cancer Research UK, found that around one in every three women who carry a damaged copy of the PALB2 gene will develop breast cancer by the time they reach the age of 70 (a 35 per cent lifetime risk).

This compares to about 55-60 per cent lifetime risk for women who carry a BRCA1 gene fault, and around 50 per cent for those who carry a faulty BRCA2 gene. 

The link between PALB2 and breast cancer was first made in 2007, by Cancer Research UK-funded scientists at The Institute of Cancer Research in London. But the precise extent of the increase in risk remained uncertain.

The new study, published in the New England Journal of Medicine, now offers a much clearer estimate of the risk for those who carry faults in the gene.

The team analysed genetic data from 154 families who did not carry BRCA1 or BRCA2 gene faults, including 362 people with a faulty PALB2 gene.

Study leader Dr Marc Tischkowitz, from the University of Cambridge, said: "Since the BRCA1 and BRCA2 mutations were discovered in the mid-90s, no other genes of similar importance have been found and the consensus in the scientific community if more exist we would have found them by now.

“PALB2 is a potential candidate to be 'BRCA3'. As mutations in this gene are uncommon, obtaining accurate risk figures is only possible through large international collaborations like this.”

Faults in the PALB2 gene are rare, with only a very small proportion of people worldwide carrying such changes. And the increase in risk was heavily influenced by family history of breast cancer, increasing in those with more relatives affected by the disease.

The researchers, based at Addenbrooke's Hospital, part of Cambridge University NHS Hospitals Trust, believe their findings could be used to develop more widespread testing for faults in PALB2 to help people make informed decisions about managing their risks of breast cancer.

"Now that we have identified this gene, we are in a position to provide genetic counselling and advice,” said Tischkowitz, who suggests that if a person is found to carry the mutation, they could be offered additional screening.

Professor Peter Johnson, Cancer Research UK's chief clinician, said: "We're learning all the time about the different factors that may influence a woman's chances of developing breast cancer.

“This particular mutation doesn't make people certain to develop cancer, but it's another piece of information to help women make proper informed choices about how they may help to minimise their own risk."

The findings may also impact on how some types of breast cancer are treated. The researchers speculate that since PALB2 works in a similar way to BRCA1 and 2, cells bearing the PALB2 errors could be targeted by a new class of drugs called ‘PARP inhibitors’, which seem to work most effectively in cancers linked to these gene faults.

The study was funded by the European Research Council, Cancer Research UK and multiple other international sources.


  • Antoniou, A, et al. (2014). Breast-Cancer Risk in Families with Mutations in PALB2 New England Journal of Medicine, 371 (6), 497-506 DOI: 10.1056/NEJMoa1400382