The Cost-Effectiveness of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer in Norway

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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GT198 (PSMC3IP) germline variants in early-onset breast cancer patients from hereditary breast and ovarian cancer families

Genes & Cancer ◽

10.18632/genesandcancer.132 ◽

2017 ◽

Vol 8 (1-2) ◽

pp. 472-483 ◽

Cited By ~ 4

Author(s):

Stephanie Schubert ◽

Tim Ripperger ◽

Melanie Rood ◽

Anthony Petkidis ◽

Winfried Hofmann ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Early Onset ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Breast And Ovarian Cancer ◽

Germline Variants

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Expanding the Criteria forBRCAMutation Testing in Breast Cancer Survivors

Journal of Clinical Oncology ◽

10.1200/jco.2010.28.0719 ◽

2010 ◽

Vol 28 (27) ◽

pp. 4214-4220 ◽

Cited By ~ 93

Author(s):

Janice S. Kwon ◽

Angelica M. Gutierrez-Barrera ◽

Diana Young ◽

Charlotte C. Sun ◽

Molly S. Daniels ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Life Expectancy ◽

Brca Mutation ◽

Cost Effective ◽

Mutation Testing ◽

Breast Cancers ◽

Brca Testing ◽

Breast And Ovarian Cancer ◽

Quality Adjusted Life

PurposeEvery year approximately 25% of women diagnosed with breast cancer are younger than 50 years of age, and almost 10% of them have a BRCA mutation. Not all potential carriers are identified by existing criteria for BRCA testing. We estimated the costs and benefits of different BRCA testing criteria for women with breast cancer younger than 50 years.MethodsWe developed a Markov Monte Carlo simulation to compare six criteria for BRCA mutation testing: (1) no testing (reference); (2) medullary breast cancer in patients younger than 50 years; (3) any breast cancer in patients younger than 40 years; (4) triple negative (TN) breast cancer in patients younger than 40 years; (5) TN breast cancer in patients younger than 50 years; (6) any breast cancer in patients younger than 50 years. Net health benefits were life expectancy and quality-adjusted life expectancy, and primary outcome was the incremental cost-effectiveness ratio (ICER). The model estimated the number of new breast and ovarian cancer cases.ResultsBRCA mutation testing for all women with breast cancer who were younger than 50 years could prevent the highest number of breast and ovarian cancer cases, but with unfavorable ICERs. Testing women with TN breast cancers who were younger than 50 years was cost-effective with an ICER of $8,027 per year of life gained ($9,084 per quality-adjusted life-year), and could reduce subsequent breast and ovarian cancer risks by 23% and 41%, respectively, compared with the reference strategy.ConclusionTesting women with TN breast cancers who were younger than 50 years for BRCA mutations is a cost-effective strategy and should be adopted into current guidelines for genetic testing.

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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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A discrete event simulation to evaluate the cost effectiveness of germline BRCA1 and BRCA2 testing in UK women with ovarian cancer

10.1101/060418 ◽

2016 ◽

Cited By ~ 1

Author(s):

Anthony Eccleston ◽

Anthony Bentley ◽

Matthew Dyer ◽

Ann Strydom ◽

Wim Vereecken ◽

...

Keyword(s):

Ovarian Cancer ◽

Cost Effectiveness ◽

Brca Mutation ◽

Discrete Event ◽

Cost Effective ◽

Mortality Rates ◽

Brca Testing ◽

Breast And Ovarian Cancer ◽

Event Simulation ◽

Risk Reducing

AbstractObjectivesThe objective of this study was to evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 (collectively termed ‘BRCA’) testing in women with epithelial ovarian cancer, and testing for the relevant mutation in first and second degree relatives of BRCA mutation-positive individuals, compared with no testing. Female BRCA mutation-positive relatives of ovarian cancer patients could undergo risk-reducing mastectomy and/or bilateral salpingo-oophorectomy.MethodsA discrete event simulation model was developed that included the risks of breast and ovarian cancer, the costs, utilities and effects of risk-reducing surgery on cancer rates, and the costs, utilities and mortality rates associated with cancer.ResultsBRCA testing all women with epithelial ovarian cancer each year is cost-effective at a UK willingness-to-pay threshold of £20,000/QALY compared with no testing, with an ICER of £4,339/QALY. The result was primarily driven by fewer cases of breast (142) and ovarian (141) cancer and associated reductions in mortality (77 fewer deaths) in relatives over the subsequent 50 years. Sensitivity analyses showed that the results were robust to variations in the input parameters. Probabilistic sensitivity analysis showed that the probability of germline BRCA mutation testing being cost-effective at a threshold of £20,000/QALY was 99.9%.ConclusionsImplementing germline BRCA testing in all ovarian cancer patients would be cost-effective in the UK. The consequent reduction of future cases of breast and ovarian cancer in relatives of mutation-positive individuals would ease the burden of cancer treatments in subsequent years and result in significantly better outcomes and reduced mortality rates for these individuals.

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Analysis of clinical characteristics in breast cancer patients with the Japanese founder mutation of BRCA1 L63X.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.28_suppl.22 ◽

2015 ◽

Vol 33 (28_suppl) ◽

pp. 22-22

Author(s):

Reiko Yoshida ◽

Mayuko Inuzuka ◽

Tomoko Watanabe ◽

Junko Yotsumoto ◽

Takashi Kuwayama ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Patients ◽

Clinical Characteristics ◽

Founder Mutation ◽

Breast Cancers ◽

Pathological Features ◽

Breast Cancer Patients ◽

Breast And Ovarian Cancer ◽

Brca1 Mutations

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.

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Bilateral Salpingo-Oophorectomy Versus GnRH Analogue in the Adjuvant Treatment of Premenopausal Breast Cancer Patients: Cost-Effectiveness Evaluation of Breast Cancer Outcome, Ovarian Cancer Prevention and Treatment

Clinical Drug Investigation ◽

10.1007/s40261-017-0571-7 ◽

2017 ◽

Vol 37 (11) ◽

pp. 1093-1102 ◽

Cited By ~ 2

Author(s):

Gabriella Ferrandina ◽

Giulia Amadio ◽

Andrea Marcellusi ◽

Elena Azzolini ◽

Anna Puggina ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cost Effectiveness ◽

Effectiveness Evaluation ◽

Gnrh Analogue ◽

Breast Cancer Patients ◽

Premenopausal Breast Cancer ◽

Breast Cancer Outcome ◽

Prevention And Treatment ◽

Cancer Outcome

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Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population

Tumor Biology ◽

10.1177/1010428317694303 ◽

2017 ◽

Vol 39 (2) ◽

pp. 101042831769430 ◽

Cited By ~ 3

Author(s):

Mina Darooei ◽

Subhadra Poornima ◽

Bibi Umae Salma ◽

Gayatri R Iyer ◽

Akhilesh N Pujar ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Cancer Patients ◽

Pedigree Analysis ◽

Care Hospital ◽

Breast Cancer Patients ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Targeted Mutation

Global burden of breast cancer is expected to increase to >2 million new cases every year by 2030 and 10% of these are likely to have hereditary breast and ovarian cancer syndrome. Identifying these individuals by pedigree and BRCA1/2 mutation analyses will enable us to offer targeted mutation testing and appropriate counseling. This study from a tertiary care hospital showed that of the 127 breast cancer patients on treatment during 2014–2015, 24 of them fulfilled the criteria of hereditary breast and ovarian cancer syndrome after detailed verbal autopsy and pedigree analysis, and BRCA1 and 2 next-generation sequencing done after pre-test counseling revealed mutations in 13 cases (54%), these included 9 BRCA1 mutations (69%) and 4 BRCA2 mutation (31%). Subsequent post-test counseling recommended targeted mutation analysis for 64 high-risk members in these 13 families with pathogenic mutations, which will help in surveillance for early detection, appropriate management, and prevention of the disease by decreasing the burden to both family and nation. Results from this preliminary study highlight the importance of genetic counseling, pedigree analysis, and genetic testing. It can be recommended that all oncology units should have a genetic counseling service for providing appropriate support to oncologists, patients, and families to prevent unnecessary testing; however, breast cancer screening program is incomplete without evaluating for hereditary breast and ovarian cancer syndrome.

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BRCA1/2 mutation prevalence in triple-negative breast cancer patients without family history of breast and ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.15_suppl.1090 ◽

2016 ◽

Vol 34 (15_suppl) ◽

pp. 1090-1090 ◽

Cited By ~ 1

Author(s):

Kerstin Rhiem ◽

Christoph Engel ◽

Jutta Engel ◽

Dieter Niederacher ◽

Christian Sutter ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Breast Cancer Patients ◽

Breast And Ovarian Cancer ◽

History Of

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Genetic Testing and Results in a Population-Based Cohort of Breast Cancer Patients and Ovarian Cancer Patients

Journal of Clinical Oncology ◽

10.1200/jco.18.01854 ◽

2019 ◽

Vol 37 (15) ◽

pp. 1305-1315 ◽

Cited By ~ 66

Author(s):

Allison W. Kurian ◽

Kevin C. Ward ◽

Nadia Howlader ◽

Dennis Deapen ◽

Ann S. Hamilton ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

Cancer Patients ◽

Population Based ◽

Cancer Type ◽

Breast Cancer Patients ◽

Breast And Ovarian Cancer ◽

Pathogenic Variants ◽

Genetic Test Results

PURPOSE Genetic testing for cancer risk has expanded rapidly. We examined clinical genetic testing and results among population-based patients with breast and ovarian cancer. METHODS The study included all women 20 years of age or older diagnosed with breast or ovarian cancer in California and Georgia between 2013 and 2014 and reported to the SEER registries covering the entire state populations. SEER data were linked to results from four laboratories that performed nearly all germline cancer genetic testing. Testing use and results were analyzed at the gene level. RESULTS There were 77,085 patients with breast cancer and 6,001 with ovarian cancer. Nearly one quarter of those with breast cancer (24.1%) and one third of those with ovarian cancer (30.9%) had genetic test results. Among patients with ovarian cancer, testing was lower in blacks (21.6%; 95% CI, 18.1% to 25.4%; v whites, 33.8%; 95% CI, 32.3% to 35.3%) and uninsured patients (20.8%; 95% CI, 15.5% to 26.9%; v insured patients, 35.3%; 95% CI, 33.8% to 36.9%). Prevalent pathogenic variants in patients with breast cancer were BRCA1 (3.2%), BRCA2 (3.1%), CHEK 2 (1.6%), PALB2 (1.0%), ATM (0.7%), and NBN (0.4%); in patients with ovarian cancer, prevalent pathogenic variants were BRCA1 (8.7%), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), and ATM (0.6%). Racial/ethnic differences in pathogenic variants included BRCA1 (ovarian cancer: whites, 7.2%; 95% CI, 5.9% to 8.8%; v Hispanics, 16.1%; 95% CI, 11.8% to 21.2%) and CHEK2 (breast cancer: whites, 2.3%; 95% CI, 1.8% to 2.8%; v blacks, 0.1%; 95% CI, 0% to 0.8%). When tested for all genes that current guidelines designate as associated with their cancer type, 7.8% of patients with breast cancer and 14.5% of patients with ovarian cancer had pathogenic variants. CONCLUSION Clinically-tested patients with breast and ovarian cancer in two large, diverse states had 8% to 15% prevalence of actionable pathogenic variants. Substantial testing gaps and disparities among patients with ovarian cancer are targets for improvement.

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