Molecular Test for Breast Cancer

In 2018, Chief Investigator, Dr Dinny Graham identified a novel gene signature called PROSPER-2.  Her research indicated that testing for this signature could identify breast cancer patients who were at greater risk of recurrence after the removal of their tumour and therefore guide treatment choices.

Dr Graham said a subsequent clinical trial with PROSPER-2, involving the multidisciplinary teams (MDTs) of clinicians at the Westmead Breast Cancer Institute, had boosted enthusiasm about new generation personalised genomic tests.

“Whereas they were previously more cautious about using molecular tests, the MDT teams found that, for the most part, the test results confirmed their own judgement and provided reassurance for patients,” she said.

For three quarters of patients, after their cancer has been removed by surgery, the standard treatment is with endocrine therapies. These are highly effective in most cases and have the most tolerable side-effects. However, a subset of these patients are at an elevated risk of relapse and are additionally treated with chemotherapy drugs.

“The ability to predict which patients are at elevated risk is critical if we are to avoid over or under-treatment, and it is this scenario where precision medicine tools are valuable,” said Dr Graham.

“Molecular tests are not essential in all cases because the treatment recommendation is unequivocal – there’s either enough concern that the patient is recommended for additional treatment such as chemotherapy, or there is clearly a very low risk of the cancer recurring. But we found that in a quarter of the patients such a test was considered helpful to the MDT, and in up to 15% of the cases it changed the treatment recommendation.

“Commercially-available molecular tests can guide clinical decisions but they are very expensive and not affordable for many patients. As a part of the clinical trial, we confirmed that our test performs as well as the commercial tests and is much more affordable.”

Building on the promising early results, development of the PROSPER-2 test is continuing with the support of the charity Tour de Cure. Recent work has been aimed at confirming initial findings that the accuracy of the new test is comparable with the commercial tests, and translating it to allow routine delivery in pathology labs.

“We went back to a larger cohort of breast cancer patients, for whom we have quite long follow-up data, and where we could compare our genetic signature result with patient outcome,” said Dr Graham. “The results so far suggest we have good correlation.”

Dr Graham, who is the Deputy Director of the Centre for Cancer Research at The Westmead Institute for Medical Research,  said work was underway to further refine the test so that, rather than requiring specialised equipment, it could be processed in standard pathology settings and “we don’t have to go through multiple steps to get to an end point.”

“Our goal is to make the test easier to apply in our hospital pathology lab, so the specimen doesn’t have to go to an offsite facility or require a pathology department to buy an expensive piece of equipment they don’t have. This will improve turn around times and lead to better equity in test provision”.

While development of the test has some way to go before it is in routine clinical use, Dr Graham said Sydney Health Partners had been crucial in getting the project this far.

“It really kick-started the project and gave us more visibility. It attracted matched funding from our colleagues in the hospital – but just as importantly, also their enthusiasm.”