Facilitated referral pathway for genetic testing at the time of ovarian cancer diagnosis: uptake of genetic counseling and testing and impact on patient-reported stress, anxiety and depression.

BACKGROUND: Timely genetic testing at ovarian cancer diagnosis is essential as results impact front line treatment decisions. Our objective was to determine rates of genetic counseling and testing with an expedited genetics referral pathway wherein women with newly-diagnosed ovarian cancer are contacted by a genetics navigator to facilitate genetic counseling. METHODS: Patients were referred for genetic counseling by their gynecologic oncologist, contacted by a genetics navigator and offered appointments for genetic counseling. Patients completed quality of life (QoL) surveys immediately pre- and post-genetic assessment and 6 months later. The primary outcome was feasibility of this pathway defined by presentation for genetic counseling. RESULTS: From 2015 to 2018, 100 patients were enrolled. Seventy-eight had genetic counseling and 73 testing. Median time from diagnosis to genetic counseling was 34 days (range 10-189). Among patients who underwent testing, 12 (16%) had pathogenic germline mutations (BRCA1-7, BRCA2-4, MSH2-1). Sixty-five patients completed QoL assessments demonstrating stress and anxiety at time of testing, however, scores improved at 6 months. Despite the pathway leveling financial and logistical barriers, patients receiving care at a public hospital were less likely to present for genetic counseling compared to private hospital patients (56% versus 84%, P = 0.021). CONCLUSIONS: Facilitated referral to genetic counselors at time of ovarian cancer diagnosis is effective, resulting in high uptake of genetic counseling and testing, and does not demonstrate a long term psychologic toll. Concern about causing additional emotional distress should not deter clinicians from early genetics referral as genetic testing can yield important prognostic and therapeutic information.

Missed opportunities: Genetic counseling and testing among an ethnically diverse cohort of women with endometrial cancer.

OBJECTIVES: Lynch syndrome (LS) accounts for the majority of inherited endometrial cancers (EC), and the identification of probands presents a unique opportunity to treat and prevent multiple cancers. The diagnosis of EC can provide the indication for women with specific risk factors to undergo genetic testing (GT). We sought to evaluate genetic counseling referrals (GCR) and subsequent GT rates in an ethnically diverse group of high-risk women. METHODS: All women diagnosed with EC between 2011 and 2016 were identified. Risk factors for LS including age, family and personal histories of Lynch-related cancers and loss of tumor mismatch repair (MMR) protein expression were identified from laboratory and medical records. Standard two-sided statistical tests were used. RESULTS: Of 583 women diagnosed with EC, 184 (31.6%) were found to have at least one high-risk characteristic for LS. Among these high-risk women, 58% were given GCR and resulting in only 35% undergoing GT. Ten of the 65 high-risk women who had GT (15.4%) were diagnosed with Lynch syndrome, and all ten met high-risk criteria. Two women of Asian race had tumors exhibiting retained MMR protein expression despite germline testing demonstrating Lynch syndrome. CONCLUSIONS: Many high-risk women do not receive GCR despite a high rate of germline mutations among these women. Improving GCR among high-risk women will lead to more subsequent GT to identify more Lynch syndrome families and prevent additional cancers. Among our ethnically diverse cohort, two women diagnosed with LS had retained MMR protein expression. GCR should be offered to women who possess high-risk characteristics despite normal MMR protein expression.

Multigene panels in Ashkenazi Jewish patients yield high rates of actionable mutations in multiple non-BRCA cancer-associated genes.

OBJECTIVE: To evaluate the results of multigene panel testing among Ashkenazi Jewish compared with non-Ashkenazi Jewish patients. METHODS: We reviewed the medical records for all patients who underwent multigene panel testing and targeted BRCA1/2 testing at a single institution between 6/2013-1/2015. Clinical actionability for identified pathogenic mutations was characterized based on the National Comprehensive Cancer Network (NCCN) guidelines and consensus statements and expert opinion for genes not addressed by these guidelines. RESULTS: Four hundred and fifty-four patients underwent multigene panel screening, including 138 Ashkenazi Jewish patients. The median patient age was fifty-two years. Three hundred and fifty-four patients (78%) had a personal history of cancer. Two hundred and fifty-one patients had breast cancer, 49, ovarian cancer, 26, uterine cancer and 20, colorectal cancer. We identified 62 mutations in 56 patients and 291 variants of uncertain significance in 196 patients. Among the 56 patients with mutations, 51 (91%) had actionable mutations. Twenty mutations were identified by multigene panels among Ashkenazi Jewish patients, 18 of which were in genes other than BRCA1/2. A review of targeted BRCA1/2 testing performed over the same study period included 103 patients and identified six mutations in BRCA1/2, all of which occurred in Ashkenazi Jewish patients. Among all Ashkenazi Jewish patients undergoing genetic testing, 25/183 (14%) had a mutation, 24/25 of which were actionable (96%) and 17/25 patients (68%) had mutations in non BRCA1/2 genes. CONCLUSIONS: With the rapid acceptance of multigene panels there is a pressing need to understand how this testing will affect patient management. While traditionally many Ashkenazi Jewish patients have undergone targeted BRCA1/2 testing, our data suggest consideration of multigene panels in this population as the majority of the results are clinically actionable and often in genes other than BRCA1/2.

Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening.

OBJECTIVE: The availability of next-generation sequencing and identification of multiple cancer-related genes has caused a shift away from single gene testing towards multi-gene panel testing for hereditary cancer syndromes. However, the utility of panels in individuals who previously underwent non-informative genetic screening has yet to be evaluated. We aim to evaluate the use of rescreening and results of multi-gene panels in this rescreened population. METHODS: We reviewed the medical records for patients who had previously undergone genetic testing and then underwent multi-gene panel testing at a single institution between 9/2013 and 11/2014. RESULTS: One hundred and twenty-seven patients with prior genetic testing underwent multi-gene panels. One hundred and four patients (82%) had a history of cancer and 118 (93%) had at least one family member with cancer. On primary testing, no pathogenic mutations were detected and 10 patients (8%) were found to have variants of uncertain significance (VUS). On repeat multi-gene panel testing, nine patients (7%) were found to have a pathogenic mutation and 53 patients (42%) were VUS not identified on prior testing. CONCLUSIONS: Seven percent of patients with non-informative primary testing were found to have a pathogenic mutation with multi-gene panels, suggesting that there is a potential benefit to be gained from rescreening. However, 42% of patients were found to have new VUS with panels, a result that can cause patients anxiety without clear clinical implications.