Genetic testing for epithelial ovarian cancer

PURPOSE To provide recommendations on genetic and tumor testing for women diagnosed with epithelial ovarian cancer based on available evidence and expert consensus. METHODS A literature search and prospectively defined study selection criteria sought systematic reviews, meta-analyses, randomized controlled trials (RCTs), and comparative observational studies published from 2007 through 2019. Guideline recommendations were based on the review of the evidence. RESULTS The systematic review identified 19 eligible studies. The evidence consisted of systematic reviews of observational data, consensus guidelines, and RCTs. RECOMMENDATIONS All women diagnosed with epithelial ovarian cancer should have germline genetic testing for BRCA1/2 and other ovarian cancer susceptibility genes. In women who do not carry a germline pathogenic or likely pathogenic BRCA1/2 variant, somatic tumor testing for BRCA1/2 pathogenic or likely pathogenic variants should be performed. Women with identified germline or somatic pathogenic or likely pathogenic variants in BRCA1/2 genes should be offered treatments that are US Food and Drug Administration (FDA) approved in the upfront and the recurrent setting. Women diagnosed with clear cell, endometrioid, or mucinous ovarian cancer should be offered somatic tumor testing for mismatch repair deficiency (dMMR). Women with identified dMMR should be offered FDA-approved treatment based on these results. Genetic evaluations should be conducted in conjunction with health care providers familiar with the diagnosis and management of hereditary cancer. First- or second-degree blood relatives of a patient with ovarian cancer with a known germline pathogenic cancer susceptibility gene variant should be offered individualized genetic risk evaluation, counseling, and genetic testing. Clinical decision making should not be made based on a variant of uncertain significance. Women with epithelial ovarian cancer should have testing at the time of diagnosis.

Download Full-text

Epithelial Ovarian Cancer Metastatic to the Central Nervous System and a Family History Concerning for Hereditary Breast and Ovarian Cancer—A Potential Relationship

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000489 ◽

2015 ◽

Vol 25 (7) ◽

pp. 1232-1238 ◽

Cited By ~ 7

Author(s):

Amelia M. Jernigan ◽

Haider Mahdi ◽

Peter G. Rose

Keyword(s):

Ovarian Cancer ◽

Central Nervous System ◽

Nervous System ◽

Genetic Testing ◽

Family History ◽

Epithelial Ovarian Cancer ◽

Survival Outcomes ◽

Breast And Ovarian Cancer ◽

Cns Metastasis ◽

Potential Relationship

ObjectivesTo estimate the frequency of hereditary breast and ovarian cancer (HBOC) in women with central nervous system (CNS) metastasis from epithelial ovarian cancer (EOC) and to evaluate for a potential relationship between HBOC status and survival.Methods and MaterialsA total of 1240 cases of EOC treated between 1995 and 2014 were reviewed to identify CNS metastasis. Demographics, treatment, family history, genetic testing, and survival outcomes were recorded. Women were then classified as HBOC+ or HBOC− based on histories and genetic testing results. Kaplan-Meier survival curves and univariable Cox proportional hazards models were used.ResultsOf 1240 cases, 32 cases of EOC with CNS metastasis were identified (2.58%). Median age was 52.13 (95% confidence interval [CI], 40.56–78.38) years, and 87.10% had stage III to IV disease. Among those with documented personal and family history, 66.7% (20/30) were suspicious for HBOC syndrome. Among those who underwent germline testing, 71.43% (5/7) had a pathogenic BRCA mutation. The median time from diagnosis to CNS metastasis was 29.17 (95% CI, 0–187.91) months. At a median survival of 5.97 (95% CI, 0.20–116.95) months from the time of CNS metastasis and 43.76 (95% CI, 1.54-188.44) months from the time of EOC diagnosis, 29 women died of disease. Univariate Cox proportional hazard models were used to compare HBOC− to HBOC+ women and did not reveal a significant difference for survival outcomes.ConclusionsConfirmed BRCA mutations and histories concerning for HBOC syndrome are common in women with EOC metastatic to the CNS. We did not demonstrate a relationship between HBOC status and survival outcomes, but were not powered to do so.

Download Full-text

Effects of initiating in-office germline testing in safety net clinic patients with epithelial ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.1588 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 1588-1588

Author(s):

Scott Jordan ◽

Samantha Spring ◽

Matthew Schlumbrecht ◽

Marilyn Huang

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Maintenance Therapy ◽

Epithelial Ovarian Cancer ◽

Intervention Group ◽

Safety Net ◽

Clinic Visit ◽

Control Group ◽

Test Results ◽

Germline Testing

1588 Background: Germline genetic mutations occur in approximately 25% of women with epithelial ovarian cancers. Recent advances in frontline maintenance therapy for patients with hereditary breast and ovarian cancer syndrome make timely germline testing critical. Adherence to genetic testing remains low (approximately 30% nationally), including at our safety net hospital where germline testing by a genetic counselor was performed in only 38% of patients. After initiating in-office genetic testing, our aim was to compare current patients with historical controls to determine whether this intervention shortened the time to testing and results. Methods: IRB approval was obtained. Patients seen for a diagnosis of epithelial ovarian cancer between 4/1/2018 and 12/31/2019 were identified. Patients with only one visit or those who received testing elsewhere were excluded. Patient and visit data were abstracted for each visit during the study period. Comparison was made between patients treated before (control cohort) and after in-office testing was initiated (intervention cohort) on 5/21/2019. Categorical variables were compared using Chi Squared and Fisher’s Exact test. Mann Whitney U test was used to compare time from first clinic visit to the date of genetic testing and to the reporting of test results in the chart. All tests were two-sided and significance was set at p = 0.05. Results: 74 patients were identified and 504 clinic visits were analyzed. 57 (77%) patients were White Hispanic, 15 (20.3%) were Black, and 2 (2.7%) were White non-Hispanic. 56 (75.7%) underwent germline testing. Overall median time to testing from the first clinic visit was 21.2 weeks, and median time to reporting of results was 37 weeks. Though there was no significant difference in testing rate between the cohorts, the time to the date of genetic testing in the intervention group was approximately one-third as long as in the control group (9.6 vs 32.1 weeks, p < 0.001). Among the 52 patients with reported genetic results, results were recorded in a clinic note at 4.1 weeks from first visit in the intervention group, compared with 28.8 weeks in the control group (p < 0.001). In the intervention group, during clinic visits without genetics performed to date, testing was performed at that visit 25% of the time. Conclusions: By initiating in-office testing, time to testing and receipt of results were meaningfully shortened. Removing delays to test results will greatly improve the ability of our patients to receive potentially life-saving maintenance therapy following front line treatment.

Download Full-text

Cost Comparison of Genetic Testing Strategies in Women With Epithelial Ovarian Cancer

Journal of Oncology Practice ◽

10.1200/jop.2016.011866 ◽

2017 ◽

Vol 13 (2) ◽

pp. e120-e129 ◽

Cited By ~ 5

Author(s):

Jonathan R. Foote ◽

Micael Lopez-Acevedo ◽

Adam H. Buchanan ◽

Angeles Alvarez Secord ◽

Paula S. Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Family History ◽

Epithelial Ovarian Cancer ◽

Decision Model ◽

Deleterious Mutation ◽

Cost Comparison ◽

Sensitivity Analyses ◽

Deleterious Mutations ◽

Testing Strategies

Purpose: The advent of multigene panels has increased genetic testing options for women with epithelial ovarian cancer (EOC). We designed a decision model to compare costs and probabilities of identifying a deleterious mutation or variant of uncertain significance (VUS) using different genetic testing strategies. Methods: A decision model was developed to compare costs and outcomes of two testing strategies for women with EOC: multigene testing (MGT) versus single-gene testing for BRCA1/2. Outcomes were mean cost and number of deleterious mutations and VUSs identified. Model inputs were obtained from published genetic testing data in EOC. One-way sensitivity analyses and Monte Carlo probabilistic sensitivity analyses were performed. Results: No family history model: MGT cost $1,160 more on average than BRCA1/2 testing and identified an additional 3.8 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $30,812 and identified 5.4 additional VUSs. Family history model: MGT cost $654 more on average and identified an additional 7.0 deleterious mutations for every 100 women tested. For each additional deleterious mutation identified, MGT cost $9,909 and identified 2.6 additional VUSs. Conclusion: MGT was associated with a higher additional cost per deleterious mutation identified and a higher ratio of VUS burden to actionable information in women with no family history as compared with women with a family history. Family history should be considered when determining an initial genetic testing platform in women with EOC.

Download Full-text

Addendum: Shin, W.; et al. The Knowledge and Attitude of Patients Diagnosed with Epithelial Ovarian Cancer towards Genetic Testing. Int. J. Environ. Res. Public Health 2021, 18, 2312

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18084043 ◽

2021 ◽

Vol 18 (8) ◽

pp. 4043

Author(s):

Wonkyo Shin ◽

Gowoon Jeong ◽

Yedong Son ◽

Sang-Soo Seo ◽

Sokbom Kang ◽

...

Keyword(s):

Public Health ◽

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer ◽

Environmental Research ◽

Knowledge And Attitude

The authors would like to add the following information to the “Funding” section of their paper published in the International Journal of Environmental Research and Public Health [...]

Download Full-text

A universal genetic testing initiative for patients with high-grade, non-mucinous epithelial ovarian cancer and the implications for cancer treatment

Gynecologic Oncology ◽

10.1016/j.ygyno.2017.05.037 ◽

2017 ◽

Vol 146 (2) ◽

pp. 399-404 ◽

Cited By ~ 24

Author(s):

Erica M. Bednar ◽

Holly D. Oakley ◽

Charlotte C. Sun ◽

Catherine C. Burke ◽

Mark F. Munsell ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Treatment ◽

Epithelial Ovarian Cancer ◽

High Grade

Download Full-text

Prevalence and opinions regarding BRCA genetic testing and counseling in a racially and ethnically diverse population of women with epithelial ovarian cancer

Gynecologic Oncology ◽

10.1016/j.ygyno.2020.05.454 ◽

2020 ◽

Vol 159 ◽

pp. 262-263

Author(s):

R. Borczuk ◽

M.A. Gardin ◽

O.R. Khouri ◽

S.M. Dolan ◽

S.K. Gorobetz ◽

...

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer ◽

Ethnically Diverse ◽

Diverse Population ◽

Brca Genetic Testing ◽

Testing And Counseling

Download Full-text

Mainstreaming Genetic Testing for Epithelial Ovarian Cancer by Oncology Providers: A Survey of Current Practice

JCO Precision Oncology ◽

10.1200/po.21.00409 ◽

2022 ◽

Author(s):

Megan A. Czekalski ◽

Rachelle C. Huziak ◽

Andrea L. Durst ◽

Sarah Taylor ◽

Phuong L. Mai

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Epithelial Ovarian Cancer ◽

Insurance Coverage ◽

Panel Testing ◽

Timely Access ◽

Poor Treatment ◽

Testing Practices ◽

Oncology Providers ◽

Cancer Network

PURPOSE With limitations in early detection and poor treatment response, ovarian cancer is associated with significant morbidity and mortality. Up to 25% of epithelial ovarian cancer (EOC) is related to a hereditary predisposition. Current National Comprehensive Cancer Network guidelines recommend that all individuals diagnosed with EOC be offered germline genetic testing. Although this would ideally be performed by genetics professionals, a shortage of genetic counselors can affect timely access to these services. This study sought to investigate the current genetic testing practices of oncology providers to determine the feasibility of oncologist-led genetic testing for patients with EOC. METHODS A survey was distributed to members of the Society of Gynecologic Oncologists with questions regarding timing, frequency, and type of cancer genetic testing, referrals to genetics professionals, confidence with aspects of genetic testing, and any barriers to these processes. RESULTS We received 170 evaluable responses. Eighty-five percent of providers always ordered genetic testing for patients with EOC. Most providers ordered germline multigene panel testing (95.8%), generally at diagnosis (64.5%). Provider confidence with the genetic testing process was generally high and significantly differed by providers' testing practices, namely, respondents who reported always ordering genetic testing tended to be more confident in ordering testing ( P = .008), interpreting results ( P = .005), and counseling a patient ( P = .002). Patient disinterest and concerns for insurance coverage were commonly cited as barriers to testing and referrals. CONCLUSION The findings from this study suggest that oncologist-led genetic testing for patients with EOC, with referrals to genetics professionals when appropriate, has the potential to be a viable alternative service delivery model to increase access to genetic testing for patients diagnosed with EOC.

Download Full-text