A Clinical Trial to Increase the Identification, Genetic Counseling Referral and Genetic Testing of Women at risk for Hereditary Breast and/or Ovarian Cancer

1575 Background: Genetic testing for at risk non-cancer patients continues to increase (Guo F, et al Cancer 2020). We identified a high risk of familial breast and ovarian cancer in rural eastern North Carolina, and created a systematic approach for genetic screening, counseling and testing. Methods: A family history questionnaire was designed to assess for the risk for hereditary breast and ovarian cancer (HBOC) using NCCN guidelines, and used at key intake points within the unaffected population to determine eligibility for genetic testing. First it was offered at the time of all mammograms. Second, we offered it in the primary gynecology care setting to capture younger patients not participating in screening mammography. Patients meeting HBOC criteria were sent a letter and two phone calls to schedule genetic counseling. Analysis via descriptive statistics. Results: 3000 rural women screened using our systematic approach to genetic risk assessment. 22.4% (673/3000) of female patients met NCCN criteria for HBOC panel testing. All offered consultation and counseling. With a backlog to see patients due to higher than expected accrual, 217 patients have completed pre-test genetic counseling, 201 completed local 19-gene panel test, and 201 had post-test counseling. Germline mutations (=>1) that predict for genetic susceptibility to cancer(s) occur in 7.8% of our screened and tested population. Currently 1 in 400 patients screened in our unaffected population carry a BRCA mutation, and 1 in 200 carry some pathogenic mutation that increases risk for HBOC. Conclusions: This rural model of screening and prevention of at risk patients for HBOC is successful at detecting pathogenic mutations in unaffected patients before they are diagnosed with cancer. Interestingly, the rate of positivity in the unaffected population (meeting criteria) is as high as the known breast cancer population rate of germline mutations (5-10%), validating the use of testing guidelines with our model. Discovering this susceptibility before a cancer diagnosis resulted in appropriate high risk management with prevention and risk reduction strategies. We plan to expand this model to the male screening population in 2021, and streamline genetic assessment and testing for the larger population at risk by engaging more rural primary care clinics over time to increase testing compliance. We also plan to consider broader gene panels as newer mutations become linked to HBOC. Clinical trial information: UMCIRB 19-001052.

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Breadth of Genetic Testing Selected by Patients at Risk of Hereditary Breast and Ovarian Cancer

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000001122 ◽

2018 ◽

Vol 28 (1) ◽

pp. 26-33 ◽

Cited By ~ 6

Author(s):

J. Brian Szender ◽

Jasmine Kaur ◽

Katherine Clayback ◽

Mollie L. Hutton ◽

June Mikkelson ◽

...

Keyword(s):

Ovarian Cancer ◽

At Risk ◽

Genetic Counseling ◽

Genetic Testing ◽

Confidence Interval ◽

Categorical Variables ◽

Breast And Ovarian Cancer ◽

Clinical Genetic ◽

Patients At Risk ◽

The Impact

ObjectiveThe aim of this study was to evaluate the ability of patients at risk of hereditary breast and ovarian cancer (HBOC) syndrome to select the extent of genetic testing personally preferred and the impact of demographic factors on the breadth of testing pursued.MethodsA single-institution cohort was enumerated consisting of patients referred for clinical genetic counseling secondary to risk of HBOC syndrome. This was a retrospective study of consecutive patients seen for genetic counseling; all patients completed an epidemiologic questionnaire and provided personal and family medical histories. Patients meeting guidelines for testing were offered testing at 3 levels: single gene/condition (Single), small panels with highly penetrant genes (Plus), and large panels with high and moderately penetrant genes (Next). Associations between personal or family-related factors and breadth of testing selected were investigated. Continuous and categorical variables were compared using Student t and χ2 tests, as appropriate. Joint classification tables were used to test for effect modification, and a log-binomial model was used to compute rate ratios (RR) with a threshold of P < 0.05 considered significant.ResultsWe identified 253 patients who underwent genetic counseling for HBOC syndrome. Most patients were personally affected by cancer (63.6%), reported at least some college (79.2%), met the National Comprehensive Cancer Network guidelines for BRCA testing (94.5%), and opted to undergo genetic testing (94.1%). Most (84.9%) patients opted for panel testing. An increased likelihood of choosing Next-level testing was found to be associated with patients having any college experience (RR, 1.53; 95% confidence interval, 1.02–2.30), as well as being unaffected by cancer (RR, 1.30; 95% confidence interval, 1.03–1.64).ConclusionsClinical genetic counseling is a highly specialized service, which should be provided to patients at risk of hereditary cancer syndromes. Although some epidemiologic factors can predict a patient's preference for testing breadth, patients were sufficiently able to self-identify the level of testing they were comfortable with after receiving genetic counseling. Most practitioners do not have the time or expertise to provide the degree of counseling needed to enable and empower patients to choose the level of testing they are comfortable with. When available, referral to genetic counselors remains an important component of comprehensive care for women with a personal or family history of cancer suggestive of hereditary risk.

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Identification and management of familial breast cancer in Austria

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2017-0025 ◽

2017 ◽

Vol 32 (2) ◽

Cited By ~ 1

Author(s):

Christian F. Singer ◽

Yen Y. Tan ◽

Christine Rappaport

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Familial Breast Cancer ◽

Prophylactic Surgery ◽

Management Options ◽

Counseling And Testing ◽

Legal Implications

AbstractAimThe aim of this study is to review the legal implications, the technology, the indications and the management of women with a familial background of breast and/or ovarian cancer.MethodsWe have reviewed the literature and national Austrian guidelines to describe the uptake of genetic counseling and the management options offered in Austria.ResultsGenetic testing for theConclusionWhile readily available country-wide counseling has led to an increase in counseling and testing, Austrian legislation mandates “non-directional counseling” resulting in a comparatively low uptake of prophylactic surgery.

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The effect of referral for genetic counseling on genetic testing and surgical prevention in women at high risk for ovarian cancer: Results from a randomized controlled trial

Cancer ◽

10.1002/cncr.30190 ◽

2016 ◽

Vol 122 (22) ◽

pp. 3509-3518 ◽

Cited By ~ 4

Author(s):

Charles W. Drescher ◽

J. David Beatty ◽

Robert Resta ◽

M. Robyn Andersen ◽

Kate Watabayashi ◽

...

Keyword(s):

Ovarian Cancer ◽

Randomized Controlled Trial ◽

Genetic Counseling ◽

Genetic Testing ◽

High Risk ◽

Controlled Trial ◽

Randomized Controlled ◽

Surgical Prevention

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Access to Genetic Testing Impacts Oncologists´ Decisions on Ovarian Cancer Personalized Treatment: Lessons Learned From a National Program in Greece

Journal of Global Oncology ◽

10.1200/jgo.18.55800 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 74s-74s

Author(s):

I. Boukovinas ◽

G. Lypas ◽

M. Liontos ◽

C. Andreadis ◽

C. Papandreou ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Cancer Patients ◽

Family Members ◽

Brca2 Gene ◽

Free Access ◽

National Program ◽

Mutation Carriers ◽

Counseling And Testing

Background: State health insurance authorities in Greece do not reimburse genetic testing for cancer predisposition. The Hellenic Society of Medical Oncology has launched and carries out a national program covering genetic testing for BRCA1/2 mutations detection, with the financial support of pharmaceutical industry. Aim: This analysis evaluates how, during this program, access to genetic testing transformed the oncologists' therapeutic approach toward their ovarian cancer patients and how the results impacted treatment decisions concerning PARP inhibitors. Adoption of testing by healthy relatives and timing of testing in the disease continuum were also evaluated. Methods: Adult patients with high-grade epithelial ovarian carcinoma, irrespectively of family history or age at diagnosis were eligible for this program. Genetic counseling was recommended before testing, and both were offered at no financial cost. First degree family members of pathogenic mutation carriers were also offered free counseling and testing. Results: From March 2015 through January 2018, 708 patients were enrolled and tested. One hundred and forty seven (20.7%) mutation carriers were identified, 102 (14.4%) in BRCA1 and 45 (6.3%) in BRCA2 gene. Testing was more often pursued at initial diagnosis (61%) than at recurrence (39%), as recorded for 409 patients with available relevant information. During the 1st year of the program, average monthly tests performed were 25.1, while during the 3rd year this number increased to 34.3 tests per month. Among patients who tested positive for deleterious BRCA1/2 mutations, relapse was reported in 58 patients, 94.8% of which (n= 55) received treatment with the PARP inhibitor olaparib as per its indication. Family members of 21 patients (14.3%), out of the 147 who tested positive, received genetic counseling and testing for the mutation identified in the context of the program. Conclusion: Free access to genetic testing for BRCA1/2 for ovarian cancer patients and genetic consultation facilitates testing uptake, affects common clinical practice & has major impact on patients and their families. Still, diffusion of genetic information and broader testing of family members require further efforts by the oncological community.

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EPV160/#618 Global assessment of guidelines for BRCA1/2 genetic testing: call to action in health equity for women and families at risk for hereditary ovarian cancer

10.1136/ijgc-2021-igcs.230 ◽

2021 ◽

Author(s):

BN Hughes ◽

JA Rauh-Hain ◽

TJ Herzog ◽

S Cummings ◽

OL O’Hanlon ◽

...

Keyword(s):

Ovarian Cancer ◽

At Risk ◽

Genetic Testing ◽

Health Equity ◽

Global Assessment ◽

Hereditary Ovarian Cancer ◽

Call To Action

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Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium

JCO Precision Oncology ◽

10.1200/po.18.00060 ◽

2018 ◽

pp. 1-14 ◽

Cited By ~ 4

Author(s):

Maria I. Carlo ◽

Veda N. Giri ◽

Channing J. Paller ◽

Wassim Abida ◽

Joshi J. Alumkal ◽

...

Keyword(s):

Prostate Cancer ◽

Clinical Trial ◽

Clinical Trials ◽

Genetic Counseling ◽

Genetic Testing ◽

Working Group ◽

Advanced Disease ◽

Treatment Selection ◽

Cancer Clinical Trials ◽

Cascade Testing

Purpose Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials. Methods The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research. Results Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies. Conclusion As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease.

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BRCA testing in women with high-grade serous ovarian cancer: gynecologic oncologist-initiated testing compared with genetics referral

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2020-001261 ◽

2020 ◽

Vol 30 (11) ◽

pp. 1757-1761

Author(s):

Sabrina Piedimonte ◽

Joanne Power ◽

William D Foulkes ◽

Evan Weber ◽

Laura Palma ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Median Time ◽

High Grade ◽

Peritoneal Carcinoma ◽

Gynecologic Oncologist ◽

Pathogenic Variants ◽

Cancer Susceptibility Genes ◽

Genetics Referral

ObjectiveUp to 15% of patients with high-grade serous ovarian, tubal, or peritoneal carcinoma harbor a mutation in BRCA genes. Early notion of mutation status may facilitate counseling, predict prognosis, and increase access to Parp-inhibitors. The aim of this study was to examine the rate of germline genetic testing in a retrospective cohort of women with high-grade serous ovarian, tubal, or peritoneal carcinoma to determine if a new pilot project of gynecologic oncologist-initiated genetic testing improved the rate of testing, after 1 year of implementation.MethodsGynecologic oncology-initiated genetic testing was implemented at a single university hospital center with input and collaboration from gynecological oncologists, nurses, and genetic counselors. All patients diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma after August 2017 were offered gynecologic oncologist- initiated genetic testing for a panel of 13 hereditary breast and ovarian cancer susceptibility genes. Data from this group was then compared with a historic cohort of patients who received traditional genetic counseling between January 2014 and August 2017 (control group). Patients that had genetic testing through a clinical trial were excluded. The primary outcome was the uptake of genetic testing in both groups. Secondary outcomes included difference in time from diagnosis to genetic result between both cohorts. Data was analyzed using SPSS 25.0 and medians (ranges) were reported.ResultsA total of 152 women with high-grade serous ovarian, tubal, or peritoneal carcinoma were included in this study. Between January 2014 to July 2017 there were 108 patients with high-grade serous ovarian, tubal, or peritoneal carcinoma, among which 50.9% (n=54) underwent genetic testing following referral to genetics. The prevalence of BRCA pathogenic variants was 25.9% (14/54): 9.2% (5/54) in BRCA1 and 16.7% (9/54) in BRCA2. The median time from diagnosis to genetics referral was 53 days (range; 3–751), and median time from diagnosis to test result disclosure was 186 days (range; 15–938). After 1 year of implementation of the gynecologic oncologist-initiated genetic testing model, among 44 women diagnosed with high-grade serous ovarian, tubal, or peritoneal carcinoma, 86.2% underwent genetic testing. The median time from diagnosis to result disclosure decreased to 58 days, representing a reduction of 128 days, or 4.27 months (P<0.001). Reasons for non-testing included refusal, death, and follow-up at another hospital. The prevalence of germline BRCA1/2 pathogenic variants was 21% (8/38).ConclusionGynecologic oncologist-initiated genetic testing at the time of high-grade serous ovarian, tubal, or peritoneal carcinoma diagnosis leads to increased uptake and decreased delays in testing compared with referral for traditional genetic counseling.

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