Major study of genetics of breast cancer provides new clues to susceptibility to the disease

Professor  Melissa Southey

An international collaborative study, including researchers from Monash University are at the forefront of the discovery of seventy-two new genetic variants that predict the risk of developing breast cancer.

The findings, released last week in two papers, are the result of work by the OncoArray Consortium, a huge endeavor involving 550 researchers from about 300 different institutions in six continents. In total, they analysed genetic data from 275,000 women, of whom 146,000 had been diagnosed with breast cancer.

65 of the newly discovered variants are common variants that predict breast cancer risk and a further seven specifically predict risk of oestrogen receptor-negative breast cancer – these are tumours that do not respond to hormonal therapies, such as the drug tamoxifen.

Associate Professor Roger Milne, Head of the Cancer Epidemiology and Intelligence Division at Cancer Council Victoria and one of the lead investigators on the study, said: “These findings add substantially to our understanding of the inherited causes of breast cancer. This study also allowed us to confirm many genetic variants that we had previously suspected were implicated in breast cancer risk. These findings help explain why women with a family history have a higher risk of breast cancer.”

“The findings will also inform improved risk prediction, both for the general population and for BRCA1 mutation carriers, the latter being more likely to develop oestrogen receptor-negative disease,” says Associate Professor Milne, who also holds an honorary appointment at the University of Melbourne. “A better understanding of the biological basis of oestrogen receptor negative breast cancer could lead to more effective preventive interventions and treatments.”

Combining epidemiological data with other data from breast tissue the researchers were able to make plausible predictions about the target genes involved with risk.

“Data from these large international genomic studies, combined with information on other known risk factors, will allow better breast cancer risk assessment and help identify an important group of women in the population who are at high risk of breast cancer. They are also likely to provide a basis for a change in the way we practice breast screening for early detection of breast cancer” said Professor Melissa Southey Chair of Precision Medicine at Monash University.

“In many countries, screening by mammography is offered from age 50; those at increased risk from having a family history can be offered screening earlier, or more often, and those at particularly high risk can be offered screening by MRI, which is more sensitive. This study opens the door for new genetic risk scores to be included in identifying women at increased or high risk,” said Professor Southey.

Cancer Council Victoria’s Professor Graham Giles said: “Given the size of these studies, we expected that we would find a lot of new breast cancer risk variants, but the study tells us a lot more about which genes are involved, revealing many previously unsuspected genes and genetic mechanisms underlying breast cancer. This should provide guidance for a lot of future research.”