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Genetics behind breast cancer for personalised care

Georgia

Photo credit: QIMR Berghofer MRI

Professor Georgia Chenevix-Trench

QIMR Berghofer Medical Research Institute | 2017 | $6,601,226

Breast cancer is the second most common cause of cancer death in Australian women.1

Despite improvements in prevention, detection and treatment, breast cancer is still the most common cancer in women.1 A more personalised approach for breast cancer risk prediction and treatment is set to be the next model of patient care.

Professor Georgia Chenevix-Trench and the team at QIMR Berghofer Medical Research Institute are unlocking some of the complex genetics behind breast cancer in order to provide more risk prediction and potentially novel treatments, with a possibility for prevention.

They are looking to understand how particular variants in the genetic code work and what the implications are for the women who carry them.

‘At the moment every woman who carries one of these mutations (in BRCA1 and 2 genes) are given the same risks,’ Professor Chenevix-Trench said.

‘If we can tell people much more precisely, for example, their risk of getting breast cancer in the next ten years is very low then they might defer having their breasts removed.’

Professor Chenevix-Trench leads an international team (CIMBA) looking to try and understand why not all women who carry a mutation in the BRCA1 and 2 genes get breast cancer and why some people are more susceptible.

‘We found that there are many common genetic variants, which each have a very small effect on risk but collectively can have quite a big effect. You can combine those small variants into what is called a polygenic risk score,’ she said.

‘The immediate challenge is to get the polygenic risk score into practice.’

In the longer term, Professor Chenevix-Trench is taking a more genome wide approach—not just BRCA 1 and 2—to try and understand how these genetic variants associated with breast cancer susceptibility operate and which of the nearby genes they affect.

‘The reason we think this is really important is that accumulating evidence from the drug companies shows that the success of getting a drug to market is doubled if the targets you are trying to pursue have got a genetic basis to it,’ Professor Chenevix-Trench said.

‘A drug doubling its success is massive in economic terms. That’s why with the 170 or so breast cancer variants we have found we think that any one of them could end up leading to a novel drug for both prevention and treatment, once we understand which gene(s) they affect.

‘The work that we’ve done will give us phenomenal insights into how breast cancer develops and I’m sure in the long term it will lead not only to better drugs for treatment but possibly for prevention.’

It is also important to understand that these genes are acting in combination with lifestyle factors, reproductive factors and breast density.

‘Better models of risk prediction should include all of those risk factors, including assessing the genetic risks,’ she said.

Professor Chenevix-Trench secured a Program Grant that provides support for teams of high calibre researchers to pursue broad based, multi-disciplinary and collaborative research activities. Teams will be expected to contribute to new knowledge at a leading international level in important areas of health and medical research.

‘The beauty of a Program Grant is the flexibility; we can use it to get some pilot data so that we are in a serious position to get some external funding. It is really value adding on what we get from NHMRC in the first place,’ she said.

‘I think this is a really exciting time in breast cancer research and genetics. There are several major international collaborations and many of them are led by Australian researchers. This is thanks to the success of organisations such as kConFab.’


1Cancer Council Australia, Breast Cancer, http://www.cancer.org.au/about-cancer/types-of-cancer/breast-cancer/ (Accessed 11 October 2017)