“MAINSTREAMING” is an important progression in the genomics revolution, say experts, but caution is needed as non-genetic specialists increasingly move into this area of medicine.

Writing in the MJA, Associate Professor Judy Kirk, Head of the Familial Cancer Service at Sydney’s Westmead Hospital, and co-authors said that the introduction of several new Medicare items for breast cancer- and ovarian cancer-related gene testing was an important step in the transition to mainstream genetic testing.

Since November 2017, any specialist or consultant physician has been able to order genetic testing for breast and ovarian cancer for eligible patients. The items cover testing for heritable mutations in seven genes, including BRCA1 and BRCA2 genes, which are responsible for 5% of female breast cancers, 15% of invasive epithelial ovarian cancers and up to 14% of male breast cancers.

Patients with a 10% risk of having a pathogenic mutation, as identified by an algorithm such as the Manchester Score, the BOADICEA Score or the BRCAPRO Score, are eligible for Medicare-funded genetic testing. Previously, genetic testing was provided to the same cohort of patients through state-funded programs in family cancer clinics and genetics services.

In an MJA InSight podcast, Professor Kirk said that there were some potential dangers as genetic testing moved into mainstream health care, including the appropriate targeting of testing.

“We’d like to see genetic testing applied in appropriate situations, and make sure that women have access to this genetic testing, but it’s important to know that most women with breast cancer don’t need a genetic test and there are guidelines about who we test, and those are agreed nationally.”

Dr Jo Burke, Manager of the Tasmanian Clinical Genetics Service, said that the mainstreaming of genetic testing for BRCA1 and BRCA2 mutations was “absolutely a positive move”.

She said that the development of improved treatment options for women with breast and ovarian cancer was the impetus behind this change in approach to testing.

“Back in the day, finding out that you had a BRCA1 or BRCA2 mutation was mainly relevant in terms of the risk to other family members and preventing other cancers,” said Dr Burke, who is a genetics counsellor. “But in the last few years, new chemotherapy options mean that [this genetic information] is just so much more important for women who are right in the middle of their breast or ovarian cancer journey. Rapid genetic testing can inform how their disease is managed.”

Professor Ingrid Winship, Executive Director of Research for Melbourne Health and the Chair of Adult Clinical Genetics at the University of Melbourne, said that the mainstreaming of genomics into general health care was one of her goals when she took on the role at the Royal Melbourne Hospital in 2006.

“There are obviously cautionary notes around mainstreaming genomics,” Professor Winship told MJA InSight. “It has to be done with process and with caution, but genomics is way too big to be held in a restricted area of healthcare.”

Professor Winship said that the MJA article clearly articulated the caution required in both the ordering of genetic tests, and the interpretation of the results.

“This kind of testing has major implications for self and for family — psychosocial issues, ethical issues, the potential for insurance prejudice. This is particularly the case if you are considering not just the primary person who has breast cancer, but perhaps her 30-year-old daughter who is making the decision to have a predictive genetic test or not,” Professor Winship said. “We want to keep the healthy, healthy, but we don’t want to make someone sick with fear, so it’s about getting that balance.”

Professor Winship said that the interpretation of results was complex. She said that genetic variants could be clearly pathogenic (disease causing) mutations, or a normal variation that don’t have any impact upon health.

“In the middle, there are ‘variants of uncertain significance’ (VUS), and this is the most difficult result to understand because it’s not nothing. It’s not simply a normal variation, like blue eyes or green eyes, but it’s not necessarily disease-causing.”

Professor Winship said that over-interpreting such a result could mean a high-risk patient being released from screening, or a low-risk patient undergoing significant interventions, such as having her breasts and ovaries removed.

“So, we need clarity and we need certainty. This is the educative process we want to bring into mainstream clinical care – that all variants in a genome are not necessarily disease causing,” she said.

“The most important thing is that a doctor requesting any test should be confident and competent to interpret the result and to convey it to the patient in such a way as the patient understands the implications and the utility. In the main, that has been the role of clinical geneticists and genetic counsellors; through multidisciplinary approaches, there are many other medical specialists who are now quite competent in that field.”

The MJA authors highlighted a proposal to standardise the reporting of genetic variants, with five classes of variants based on the likelihood of pathogenicity. At present, Australia does not have a nationally consistent approach to reporting genetic variants.

Professor Winship said that consistency of reporting was “absolutely pivotal”. She said the Royal Melbourne Hospital had recently employed, for the first time, a variant curator to help assess genetic test results, and she called for laboratories to prominently report the interpretation of the results and their clinical utility.

Professor Kirk said that a further concern was the interpretation of a negative result.

“If we don’t find anything in those particular genes, but the family history is still pretty strong, there could still be something genetic going on, it’s just that we haven’t located it with the current genetic tests and knowledge,” she said.

Dr Burke agreed that caution was needed in the interpretation of test results and advised non-genetics clinicians to develop a close relationship with their local genetics service or family cancer centre.

“Non-genetic clinicians need to have a ‘go-to’ person – someone they can ask questions of and refer to, and get some training from, if necessary,” she said. She added that the genetics special interest group of the Clinical Oncology Society of Australia had conducted a nationwide training program for oncologists and gynaecological oncologists in 2017, which had helped many specialists to forge relationships with genetic services.

She added that the role of genetic counsellors was crucial, particularly in cases of predictive testing, where the unaffected relative of a cancer-affected patient with a BRCA1 or BRCA2 mutation elects to have genetic testing to predict future cancer risk.


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