Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian cancer patients

Abstract

SUMMARYBackground:Advances in DNA sequencing have made gene testing fast and affordable, but adaptation of clinical services to capitalise on this for patient benefit has been slow. Ovarian cancer exemplifies limitations of current systems and potential benefits of increased gene testing. Approximately 15% of ovarian cancer patients have a germline mutation in BRCA1 or BRCA2 (collectively termed ‘BRCA’) and this has substantial implications for their personal management and that of their relatives. However, in most countries implementation of BRCA testing in ovarian cancer has been inconsistent and largely unsuccessful.Methods:We developed a mainstream pathway in which BRCA testing was undertaken by cancer team members after 30 minutes online training. Patients with a mutation were sent a genetic appointment with their results. Cascade testing to relatives was performed via standard clinical genetic procedures.Findings:207 women with ovarian cancer were offered gene testing through the mainstream pathway and all accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease including 97% (32/33) women with a mutation. All mutation-positive women and ~3.5 relatives per family have been seen in genetics. Patient and clinician feedback was very positive. >95% found the pathway to be simple and effective. The pathway offers considerable reduction in time (~5-fold) and resource requirements (~13-fold) compared to the traditional genetic pathway. We estimate it would deliver £2.6M NHS cost savings per year, and would allow implementation of national testing recommendations with existing infrastructure.Interpretation:Mainstream genetic testing is effective, efficient and patient-centred and offers a mechanism for large-scale implementation of BRCA gene testing in cancer patients. The principles could be applied in many other countries and to many other areas of genomic medicine.

Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population

“…Our study population comprises 26.4% of the UK population 20. Assuming proportionate UK annual OC and BC incidence in our population (OC incidence=0.264*7400; TNBC incidence=0.264*55200)27 28 and two additional carriers identified from cascade testing29 for each index case, we incorporated the additional impact of testing all epithelial OC and TNBC in the models to detect ‘total’ BRCA  carriers in the population. Addition of testing epithelial OC/TNBC at cancer diagnosis to current detection rates will take >250 years (2286) to identify the ‘total’ BRCA  carriers in the general population.…”

Mainstreamed genetic testing for women with ovarian cancer: first-year experience

“…Systematic genetic testing for all women with high-grade non-mucinous EOC is increasing, either via oncology (MGT) or clinical genetics services. However, there is a lack of consensus as to how BRCA testing should be provided to patients with ovarian cancer,9 and this will lead to inequities in accessing testing in this group.…”

Uptake of testing for germline BRCA mutations in patients with non-mucinous epithelial ovarian cancers in Western Australia: a comparison of different genetic counseling methods

“…Mainstreaming is the provision of BRCA -specific germline testing in a routine oncology clinic by non-genetics specialists following upskilling to consent, order, interpret, and deliver results 11. Patients who tested positive for pathogenic germline mutations received their test results from the clinician who performed the mainstreaming consultation but were also referred to the Familial Cancer Clinic for further post-test counseling by a genetic counselor, and to discuss cascade testing of next-of-kin.…”