This study reports on the referrals to cancer genetics services made by Breast MDT meetings within our three cancer centres for women diagnosed with TNBC. We have demonstrated 81% (25/31) of women who fulfilled the TNBC age criteria for genetics referral at their time of diagnosis, were appropriately referred to a genetics service for discussion of genetic testing. Of this group, 68% (21/31) were women referred within our regions. These findings compare favourably with the 58.5% (10/17) appropriately referred patients described in a study on a major metropolitan cancer centre . The most prevalent PV identified in our cohort were BRCA1 PVs, which made up 50% (5/10) of the total PVs identified, followed by BRCA2 PV representing 40% (4/10) of the total PVs and a single non-BRCA1/2 PV which was an ATM:c.7271 T > G PV, representing 10% (1/10) of PVs identified. Due to small sample size, we did not see a significant difference in BRCA1/2 PV identification.
Of our total cohort who had genetic testing, 19% (10/53) of women had a PV identified, with 9% (5/53) found to carry a BRCA1 PV. Our non-BRCA1/2 detection rate amongst the women who had panel testing was 3.3% (1/30). These findings are in line with other studies [4, 15,16,17].
It is important to note that genes included in the panel testing performed in this study were not always the same, as it was reliant on what was available and appropriate at the time of testing, rather than a static selection. Regarding non BRCA1/2 PVs, it has been suggested that BARD1, BRIP1, PALB2, and RAD51C PVs may be more prevalent in women diagnosed with TNBC [15, 16]. In the timeframe of this study, only PALB2 was routinely involved in screening; however, this would not necessarily have been tested for in each person who had panel testing in this study.
Updating genetic testing for individuals with no PV identified or ‘re-contacting ‘is becoming common in clinical practice, as developments in technology and known cancer predisposition genes yield higher detection rates than previous testing available. This information may impact upon medical management for an individual at the time of their diagnosis. Various studies looking at updating genetic testing for people who previously had BRCA1/2 testing with no PV identified (not limited to TNBC), showed a PV detection rate between 4 and 11.4% [18,19,20,21]. If genetic testing was updated for the 20 women who had BRCA1/2 testing only, it would be expected that approximately one to two women would have a PV identified. Currently updated genetic testing is performed ad-hoc in our genetics services and many others, usually prompted by a referral for the individual or their relatives.
Guidelines for genetics referral and testing are changing rapidly with the increasing knowledge in cancer genetics. Since the change in guidelines for women diagnosed with TNBC, we identified 5% (11/237) of the total cohort who would now meet criteria for genetic testing, but did not at their time of diagnosis. It is possible that some of these individuals have seen an out of area or private genetics service since the guidelines changed; we do not have access to records to verify this. There are many studies looking at re-contacting patients within a genetics context, investigating how best do this when there is updated information that may benefit the patient [22,23,24,25,26]. There is no consensus or procedures in place at present to guide service delivery in re-contacting patients [22,23,24,25,26].
It is not clear whose responsibility it is to inform patients of updated genetic information. Is it the role of genetics services, specialist clinicians, general practitioners or the patients themselves [22,23,24,25]? As per the Human Genetics Society of Australasia Clinical Genetics Service Framework , our services encourage patients to re-contact the service for updated information over time. Anecdotally, we find patients rarely re-contact our genetics services for updated information. Studies have shown that the majority of patients do want to be re-contacted when relevant information is available [22, 28], suggesting other methods to facilitate this would be beneficial for our patients.
Response rates to mailed letters were examined by Sawer et al. . The authors sent a letter to patients who had had testing with no PV identified, suggesting they re-contact the service to have their testing updated. Seven months after sending the letter only 4.27% of people had seen the genetics service as a result of the letter. The authors experimented with four different versions of the letter, focusing on different benefits of further testing (ie. for the person themselves versus benefit to relatives), and found no differences in response rate. They deduced, that while the letter had a very low response rate, it did fulfil the service’s duty of care to notify patients of updated information .
Telephoning patients has also been evaluated. In a study examining contacting parents of children with intellectual disabilities to inform updated testing was available, the vast majority of parents (87%) thought re-contacting was appropriate . A higher response rate was achieved, with 36% arranging a follow up appointment as result of the phone call . While this was a very successful method, this is very labor intensive for a busy genetics service. It is unlikely that this would be possible for most genetics services without specific additional operational funding and resources.
Another method for updating genetic testing is via research projects. In the genetic testing consent process, patients provide consent for updating testing to be performed on their stored DNA. This is reliant on funded research projects to organise the re-testing and interpretation of results. The genetics service would then contact the patient, arrange clinical confirmation of the result and the necessary clinical follow up. Rather than spreading resources across all patients, this allows for focus on those individuals with a PV identified. However, is reliant on specific research projects occurring.
The European Society of Human Genetics has addressed these concerns, stating re-contacting should occur in the best interest of the patient . Responsibility should be shared between the multidisciplinary team and the patient themselves. Resources should be provided to ensure this is sustainable within the health service, including data retention, data review and sharing of information . This is especially important for regional centres where patients are located in a wide geographical area. The provision of resources, both in terms of genetic counsellors and administrative support has not kept up with the large increase in overall demand, let alone allowing for additional tasks such as outlined to occur. A professional consensus is needed to guide re-contacting patients .
For patients still engaged with clinical services, MDT meetings provide an opportunity for review of updated genetic information. Genetic counsellor attendance at MDT meetings has been shown to improve referrals for cancer genetics . In the time frame of our study, genetic counsellors were available for consult for the Breast MDT groups, however attendance was sporadic across some of our sites, due to availability within working hours or as a result of resource constraints. Advances in knowledge and technology has made genetic testing more available and extensive for patients, without a commensurate expansion of genetic counsellor roles to manage the ever greater workload . Increase in resources for genetics services to allow genetic counsellors to regularly attend MDT meetings would help ensure updated genetic information is available for patient care. Increased resources would also assist in providing dedicated time for regular quality assurance projects to identify patients who may benefit from an updated genetics review without impacting waiting times for clinical care.
Our study highlights that quality assurance projects are valuable to identify patients who may benefit from an updated genetic assessment, especially those who did not meet criteria for referral at their time of diagnosis. We found retrospective data searches easily identified these patients. Collaboration and integration of genetics services and cancer services ensured a broader spectrum of patients were included. Further consideration will be needed to examine how we can integrate routine quality assurance projects across specialties in our cancer centres to improve and update genetic information for patients within our cancer centres.
Strengths and limitations
The use of the Trakgene genetic database was a strength in this study, as it provided information on referrals across the whole state. Obtaining records from the electronic medical records was also a strength. Across both databases data entry and retention were limitations of this study. There were some inconsistencies in the data entry across both databases, which may have resulted in some women being omitted from our data searches. Where possible information was verified by manual searches, but in some cases information was unable to be verified and that individual removed from the data set.
The retrospective nature of this study was a limitation, as the testing arranged for women in this study was not all the same, but reliant on what testing was available and routine practice in the genetics services at the time. This is particularly salient with the panel testing described in this study. The small data set was also a limitation, this study could be replicated state or nation-wide to provide greater depth to the knowledge about referral rates for women with TNBC and the outcomes of their genetic testing.