Uterine lavage for the detection of ovarian cancer using an expanded gene panel

Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non- BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non- BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.

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MG-114 Clinical actionability of multi-gene panel tests for hereditary breast and ovarian cancer (HBOC)

Journal of Medical Genetics ◽

10.1136/jmedgenet-2015-103578.14 ◽

2015 ◽

Vol 52 (Suppl 2) ◽

pp. A6.1-A6

Author(s):

Leif W Ellisen ◽

Stephen E Lincoln ◽

Allison W Kurian ◽

Andrea J Desmond ◽

Shan Yang ◽

...

Keyword(s):

Ovarian Cancer ◽

Gene Panel ◽

Breast And Ovarian Cancer

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Gene panel testing of 5589 BRCA1/2 -negative index patients with breast cancer in a routine diagnostic setting: results of the German Consortium for Hereditary Breast and Ovarian Cancer

Cancer Medicine ◽

10.1002/cam4.1376 ◽

2018 ◽

Vol 7 (4) ◽

pp. 1349-1358 ◽

Cited By ~ 39

Author(s):

Jan Hauke ◽

Judit Horvath ◽

Eva Groß ◽

Andrea Gehrig ◽

Ellen Honisch ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Gene Panel ◽

Negative Index ◽

Breast And Ovarian Cancer ◽

Panel Testing ◽

Gene Panel Testing ◽

Diagnostic Setting

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Oncology Clinic-Based Hereditary Cancer Genetic Testing in a Population-Based Health Care System

Cancers ◽

10.3390/cancers12020338 ◽

2020 ◽

Vol 12 (2) ◽

pp. 338 ◽

Cited By ~ 1

Author(s):

Matthew Richardson ◽

Hae Jung Min ◽

Quan Hong ◽

Katie Compton ◽

Sze Wing Mung ◽

...

Keyword(s):

Ovarian Cancer ◽

Health Care ◽

Genetic Testing ◽

Population Based ◽

Gene Panel ◽

Wait Times ◽

Genetic Counsellor ◽

Care Providers ◽

Cancer Genetic ◽

Breast And Ovarian Cancer

New streamlined models for genetic counseling and genetic testing have recently been developed in response to increasing demand for cancer genetic services. To improve access and decrease wait times, we implemented an oncology clinic-based genetic testing model for breast and ovarian cancer patients in a publicly funded population-based health care setting in British Columbia, Canada. This observational study evaluated the oncology clinic-based model as compared to a traditional one-on-one approach with a genetic counsellor using a multi-gene panel testing approach. The primary objectives were to evaluate wait times and patient reported outcome measures between the oncology clinic-based and traditional genetic counselling models. Secondary objectives were to describe oncologist and genetic counsellor acceptability and experience. Wait times from referral to return of genetic testing results were assessed for 400 patients with breast and/or ovarian cancer undergoing genetic testing for hereditary breast and ovarian cancer from June 2015 to August 2017. Patient wait times from referral to return of results were significantly shorter with the oncology clinic-based model as compared to the traditional model (403 vs. 191 days; p < 0.001). A subset of 148 patients (traditional n = 99; oncology clinic-based n = 49) completed study surveys to assess uncertainty, distress, and patient experience. Responses were similar between both models. Healthcare providers survey responses indicated they believed the oncology clinic-based model was acceptable and a positive experience. Oncology clinic-based genetic testing using a multi-gene panel approach and post-test counselling with a genetic counsellor significantly reduced wait times and is acceptable for patients and health care providers.

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Clinical impact of multi-gene panel testing for hereditary breast and ovarian cancer risk assessment.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.1513 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. 1513-1513

Author(s):

Leif W. Ellisen ◽

Allison W. Kurian ◽

Andrea J Desmond ◽

Meredith Mills ◽

Stephen E Lincoln ◽

...

Keyword(s):

Ovarian Cancer ◽

Risk Assessment ◽

Cancer Risk ◽

Clinical Impact ◽

Gene Panel ◽

Cancer Risk Assessment ◽

Ovarian Cancer Risk ◽

Breast And Ovarian Cancer ◽

Panel Testing ◽

Gene Panel Testing

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Impact of hereditary multigene panel testing for cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.3_suppl.261 ◽

2016 ◽

Vol 34 (3_suppl) ◽

pp. 261-261

Author(s):

Nimmi S. Kapoor ◽

Jennifer Swisher ◽

Rachel E. McFarland ◽

Mychael Patrick ◽

Lisa D. Curcio

Keyword(s):

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Survivors ◽

Gene Mutation ◽

Gene Panel ◽

Personal History ◽

Panel Testing ◽

Pathogenic Mutations ◽

Gene Panel Testing ◽

History Of

261 Background: Recently, genetic testing for hereditary cancer syndromes has seen numerous advances in testing spectrum, capability, and efficiency. This may have important implications for cancer survivors and their families. The purpose of this study is to evaluate the impact of reflex genetic testing with newer multi-gene panels on patients with prior negative BRCA1/2 tests. Methods: Data was collected retrospectively from patients who underwent multi-gene panel testing at one of three sites from a single institution between 8/2013-6/2015. Those with a personal history of breast or ovarian cancer and a prior negative BRCA1/2 test were included. Results: Of 914 patients who underwent multi-gene panel tests, 187 met study inclusion criteria. Ten patients (5.3%) were found to carry 11 pathogenic mutations, including 6 patients with mutations in CHEK2, 2 patients with mutations in PTEN, and 1 patient each with mutations in the following genes: BARD1, NF1, and RAD51C. One patient had two pathogenic mutations identified—CHEK2 and BARD1. Of 10 patients with mutations, 9 had a personal history of breast cancer diagnosed at a median age of 43 (range 35-52) and 1 had ovarian cancer diagnosed at age 65. A majority of mutation carriers underwent panel testing years after their cancer diagnosis (median 6 years, range 0.5-32 years) and none with delayed testing had undergone prophylactic contralateral mastectomy prior to the discovery of their gene mutation. All patients with mutations had a family history of at least one cancer, with most having a variety of cancer diagnoses in multiple relatives. Positive panel testing results altered clinical management in most patients, including addition of breast MRI, colonoscopy, or thyroid ultrasound depending on the gene mutation. After discovery of a PTEN mutation 19 years after her initial cancer treatment, one woman underwent bilateral prophylactic mastectomy and was found to have occult ductal carcinoma in situ. Conclusions: Cancer survivorship must incorporate advances in technology that may be beneficial even years after treatment has ended. Multi-gene panel testing can be applied in survivorship settings as a useful tool to guide screening recommendations.

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Circulating tumor DNA analysis using targeted sequencing of 508 clinically actionable genes in patients with high grade serous ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.5582 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 5582-5582

Author(s):

Anniina Färkkilä ◽

Liina Salminen ◽

Kaisa Huhtinen ◽

Sakari Hietanen ◽

Seija Elisa Grenman ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Tissue ◽

Genetic Alterations ◽

Gene Panel ◽

Targeted Sequencing ◽

Primary Therapy ◽

High Grade ◽

Serous Ovarian Cancer ◽

Cancer Genes ◽

Treatment Toxicity

5582 Background: The prediction of tumor chemoresponse and treatment toxicity is crucial for optimal patient care in high grade serous ovarian cancer (HGSC). We employed a targeted sequencing panel of 508 clinically annotated cancer genes to screen for actionable genetic variants in tumor tissue and ctDNA of patients with advanced HGSC. Methods: Tumor tissue, and serial plasma samples at diagnosis and during primary therapy were obtained from five patients with FIGO Stage IIIc HGSC. All patients were surgically debulked and received standard carboplatin and paclitaxel chemotherapy. DNA isolated from tumor tissue and plasma was analyzed for genetic alterations by targeted deep-sequencing of 508 previously annotated cancer genes. Somatic variants were systematically reported for alterations related to drug sensitivity and treatment toxicity, and analyzed with respect to clinical parameters and primary therapy outcomes. Results: In tumor tissues, and the corresponding pre-treatment ctDNA, oncogenic mutations were detected at a median of 13.0 and 1.6 allelic frequencies, respectively. The mutation frequency was higher, and also more unique mutations were detected in ctDNA of patients presenting with high tumor spread. Interestingly, a de-novo ctDNA MAPK1 mutation was detected in a sample taken during chemotherapy with partial response, while, no new mutations emerged in a patient with complete response. Analysis of the pretreatment plasma ctDNA revealed profiles of low and high drug sensitivities consistent with the clinical course of the patients. In two patients, increased risk profiles for treatment toxicities were identified via e.g. GSTP1. Consistently, these two patients were forced to discontinue standard therapy. Conclusions: Panel-based targeted sequencing of ctDNA identified potentially actionable mutations, and reflected tumor heterogeneity of HGSC. Further, the ctDNA gene panel annotations showed concordance with the chemoresponse- and treatment toxicity profiles, suggesting that ctDNA gene panel maybe a feasible approach to individualize treatment of HGSC patients.

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