The Prevent Ovarian Cancer Program (POCP): Identification of women at risk for ovarian cancer using complementary recruitment approaches.

BACKGROUND: Up to 20% of high-grade serous ovarian carcinomas (HGSOC) are hereditary; however, historical uptake of genetic testing is low. We used a unique combination of approaches to identify women in Ontario, Canada, with a first-degree relative (FDR) who died from HGSOC without prior genetic testing, and offer them multi-gene panel testing. METHODS: From May 2015-Sept 2019, genetic counseling and testing was provided to eligible participants. Two recruitment strategies were employed, including self-identification in response to an outreach campaign and direct targeting of FDRs of deceased HGSOC patients treated at our institution. The rate of pathogenic variants (PV) in established/potential ovarian cancer risk genes and the benefits/challenges of each approach were assessed. RESULTS: A total of 564 women enrolled in response to our outreach campaign (n = 473) or direct recruitment (n = 91). Mean age at consent was 52 years and 96% did not meet provincial testing criteria. Genetic results were provided to 528 individuals from 458 families. The rate of PVs in ovarian cancer risk genes was highest when FDRs were diagnosed with HGSOC <60 years (9.4% vs. 3.9% ≥ 60y, p = 0.0160). Participants in the outreach vs. direct recruitment cohort had a similar rate of PVs; however, uptake of genetic testing (97% vs. 89%; p = 0.0036) and study completion (95% vs. 87%; p = 0.0062) rates were higher in the former. Eleven participants with pathogenic variants have completed risk-reducing gynecologic surgery, with one stage I HGSOC and two breast cancers identified. CONCLUSION: Overall PV rates in this large cohort were lower than expected; however, we provide evidence that genetic testing criteria in Ontario should include individuals with a deceased FDR diagnosed with HGSOC <60 years of age.

Setting a baseline: A 7-year review of referral rates and outcomes for serous ovarian cancer prior to implementation of oncologist mediated genetic testing.

OBJECTIVE: Despite guidelines recommending that all women with invasive serous ovarian cancer (SOC) are offered genetic testing, published referral and testing rates have been poor. Many centers have implemented novel genetic counseling service delivery models to increase testing rates. In light of increased awareness and implementation of small process changes at our center, this study aims to establish baseline referral rates and testing outcomes prior to diverging from the traditional model of care. METHODS: A list of women diagnosed with SOC at Princess Margaret Cancer Center (PM) between 2010 and 2016 was obtained from the PM Cancer Registry and cross-referenced against the genetics database to determine referral rates and outcomes of genetic testing. RESULTS: Of 724 women with SOC, 68% were referred for genetic counseling, with an overall testing rate of 61%. Higher referral rates were seen among women with younger ages at diagnosis and high-grade tumors. Of women tested, 22% were found to have a pathogenic variant in BRCA1/2 and 9% in another cancer gene. Notably, 24% of women with a pathogenic variant reported no family history of breast or ovarian cancer. CONCLUSION: Genetic counseling referral and testing rates for women with SOC are higher than previously reported, yet barriers to referral remain. To maximize genetic testing rates and address increasing patient volumes, clinics may be faced with integrating novel genetic counseling delivery models. Findings from this study may serve as a more accurate baseline to which large scale service delivery changes can be compared.

BRCA Mutation Status Is Not Associated With Increased Hematologic Toxicity Among Patients Undergoing Platinum-Based Chemotherapy for Ovarian Cancer.

OBJECTIVE: Women with an inherited BRCA1 or BRCA2 mutation may have an impaired ability to repair chemotherapy-induced damage as a result of a state of haploinsufficiency and may experience greater treatment-related toxicity. The objective of this study was to compare the hematologic adverse effect profiles associated with platinum-based chemotherapy in ovarian cancer patients with and without germline BRCA mutations. METHODS: We conducted a retrospective analysis of patients treated for high-grade serous ovarian cancer at Princess Margaret Cancer Center, Toronto, Ontario between January 2000 and December 2015. We included only women with known BRCA mutation status and who received first-line platinum-based chemotherapy. We compared 3 primary measures of myelosuppression (ie, hemoglobin levels, platelet counts, and neutrophil counts) before each cycle of chemotherapy in patients with and without a BRCA mutation. RESULTS: We included 130 BRCA mutation carriers and 302 noncarriers who met the eligibility criteria. There were no significant differences in baseline hemoglobin levels, neutrophil counts, or platelet counts between the groups (P ≥ 0.31). We found no significant difference in 3 measures of hematologic toxicity (ie, neutropenia, anemia, or thrombocytopenia) based on BRCA mutation status across all chemotherapy cycles (P ≥ 0.06). Although BRCA mutation carriers were more likely to experience an absolute neutrophil count below 1.0 × 10/L than noncarriers (P = 0.02), this did not translate to an increased frequency of dose reduction or dose delay. DISCUSSION: Among women with ovarian cancer, hematologic toxicity does not appear to be more frequent in BRCA mutation carriers than in noncarriers. This is reassuring for clinicians treating ovarian cancer patients with respect to dosing regimens. These findings do not support the hypothesis that a haploinsufficiency phenotype exists with respect to the repair of chemotherapy-induced double-strand DNA breaks in this high-risk population.

Next-Generation Service Delivery: A Scoping Review of Patient Outcomes Associated with Alternative Models of Genetic Counseling and Genetic Testing for Hereditary Cancer.

The combination of increased referral for genetic testing and the current shortage of genetic counselors has necessitated the development and implementation of alternative models of genetic counseling and testing for hereditary cancer assessment. The purpose of this scoping review is to provide an overview of the patient outcomes that are associated with alternative models of genetic testing and genetic counseling for hereditary cancer, including germline-only and tumor testing models. Seven databases were searched, selecting studies that were: (1) full-text articles published ≥2007 or conference abstracts published ≥2015, and (2) assessing patient outcomes of an alternative model of genetic counseling or testing. A total of 79 publications were included for review and synthesis. Data-charting was completed using a data-charting form that was developed by the study team for this review. Seven alternative models were identified, including four models that involved a genetic counselor: telephone, telegenic, group, and embedded genetic counseling models; and three models that did not: mainstreaming, direct, and tumor-first genetic testing models. Overall, these models may be an acceptable alternative to traditional models on knowledge, patient satisfaction, psychosocial measures, and the uptake of genetic testing; however, particular populations may be better served by traditional in-person genetic counseling. As precision medicine initiatives continue to advance, institutions should consider the implementation of new models of genetic service delivery, utilizing a model that will best serve the needs of their unique patient populations.