Genetic testing for BRCA1 and BRCA2 is crucial for assessing an individual’s risk of hereditary breast and ovarian cancer and other related cancers.
However, until now, genetic tests have not always been clear and can be interpreted differently by different labs, meaning people with the same DNA changes might receive different treatments, which could lead to very different outcomes.
New Zealand Familial Breast Cancer Study co-ordinator and University of Otago (Christchurch) research senior author Associate Prof Logan Walker is part of a larger international group of researchers who have developed a new standardised protocol for use in BRCA1 and BRCA2 genetic testing.
He said both men and women could carry the BRCA genes and get breast cancer, and "hundreds" were diagnosed with the genes in New Zealand each year.
However, up to 85% of those who were tested for the BRCA1 and BRCA2 genes, had results that were not always clear, and it sometimes led to unnecessary medical treatment and anxiety.
"They fall in the ‘too hard basket’ because we don’t know whether they are associated with increased risk of breast cancer and other cancers, or not.
"The patient will know that they carry this genetic change, but they won’t know whether it is associated with increased risk of disease.
"So they take away that knowledge, not knowing what it means for them or their family.
"For them, it’s a bit like sitting on a ticking time bomb. They don’t know if it is going to turn into breast or ovarian cancer — a lot of anxiety."
He said some in that situation choose to have mastectomies or ovaries removed, to reduce the possibility of getting cancer.
"Everyone will have their own perception of risk."
Prof Walker is among an international research team of 43 scientists and clinicians, led by QIMR Berghofer, in Australia, who have developed a new standardised protocol for use in BRCA1 and BRCA2 genetic testing.
He said the new protocol helped to give those with the genetic mutation a clearer picture of what the future held for them.
"The new protocol is an instruction manual for when BRCA1 and BRCA2 genetic tests are done at diagnostic labs and research labs, so that genetic counsellors, clinical geneticists and health professionals are able to look at the genetic change and then work through a series of instructions, guidelines and recommendations, so that they can work out if it is something that is clinically benign, or is it something that is pathogenic.
"There’s still a ‘too hard basket’ — there’s still some results which even with these guidelines we still don’t fully understand.
"But the new protocol will more accurately assess cancer risk for people with uncertain genetic variants."
Lead author and QIMR Berghofer researcher Prof Amanda Spurdle said the FDA and ClinGen-approved protocol combined clinical and research expertise from around the world with advanced statistical methods.
"This integration offers precise guidelines for resolving uncertain or conflicting results to help determine the clinical significance of BRCA1 or BRCA2 variants."
Fellow QIMR Berghofer researcher Mr Michael Parsons said the ability to better interpret genetic test results would help doctors give advice on the frequency of early screening such as breast scans, preventive measures such as risk-reducing surgery or medication and the best therapeutic treatments for people with cancer.
"Improving diagnostic results will also help clinicians decide whether to test close relatives, to prevent or catch the disease earlier in family members."
The international research team will continue contributions to a central global resource of information about genes and variants to improve patient care.
