Risk Assessment, Genetic Counseling, and Genetic Testing for<i>BRCA-</i>Related Cancer in Women

Nelson, Heidi D; Pappas, Miranda; Cantor, Amy; Haney, Elizabeth M; Holmes, Rebecca

doi:10.1001/jama.2019.8430

Cited by 114 publications

(62 citation statements)

References 169 publications

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“…We are against indiscriminate large-scale commercial panel testing without well-established clinical benefit/utility in the population-testing context. The low incidence of moderate penetrance genes, poor precision, and wide confidence intervals around prevalence and penetrance estimates require more data on the clinical significance of pathogenic variants in multigene panels, and these are reasons against currently implementing large multigene panel testing in the general population [51,52]. The USPSTF currently recommends against population testing in the general population [51].…”

Section: Discussionmentioning

confidence: 99%

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Manchanda

Sun

Patel

et al. 2020

Cancers

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Clinical criteria/Family history-based BRCA testing misses a large proportion of BRCA carriers who can benefit from screening/prevention. We estimate the cost-effectiveness of population-based BRCA testing in general population women across different countries/health systems. A Markov model comparing the lifetime costs and effects of BRCA1/BRCA2 testing all general population women ≥30 years compared with clinical criteria/FH-based testing. Separate analyses are undertaken for the UK/USA/Netherlands (high-income countries/HIC), China/Brazil (upper–middle income countries/UMIC) and India (low–middle income countries/LMIC) using both health system/payer and societal perspectives. BRCA carriers undergo appropriate screening/prevention interventions to reduce breast cancer (BC) and ovarian cancer (OC) risk. Outcomes include OC, BC, and additional heart disease deaths and incremental cost-effectiveness ratio (ICER)/quality-adjusted life year (QALY). Probabilistic/one-way sensitivity analyses evaluate model uncertainty. For the base case, from a societal perspective, we found that population-based BRCA testing is cost-saving in HIC (UK-ICER = $−5639/QALY; USA-ICER = $−4018/QALY; Netherlands-ICER = $−11,433/QALY), and it appears cost-effective in UMIC (China-ICER = $18,066/QALY; Brazil-ICER = $13,579/QALY), but it is not cost-effective in LMIC (India-ICER = $23,031/QALY). From a payer perspective, population-based BRCA testing is highly cost-effective in HIC (UK-ICER = $21,191/QALY, USA-ICER = $16,552/QALY, Netherlands-ICER = $25,215/QALY), and it is cost-effective in UMIC (China-ICER = $23,485/QALY, Brazil−ICER = $20,995/QALY), but it is not cost-effective in LMIC (India-ICER = $32,217/QALY). BRCA testing costs below $172/test (ICER = $19,685/QALY), which makes it cost-effective (from a societal perspective) for LMIC/India. Population-based BRCA testing can prevent an additional 2319 to 2666 BC and 327 to 449 OC cases per million women than the current clinical strategy. Findings suggest that population-based BRCA testing for countries evaluated is extremely cost-effective across HIC/UMIC health systems, is cost-saving for HIC health systems from a societal perspective, and can prevent tens of thousands more BC/OC cases.

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Section: Discussionmentioning

confidence: 99%

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Manchanda

Sun

Patel

et al. 2020

Cancers

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“… Note: The list consists of data used in criteria for further genetic risk evaluations in the National Comprehensive Cancer Network Version 3.2019, Breast and/or Ovarian Cancer Genetic Assessment. 6 The italicized text indicates data that were extracted from the Enterprise Data Warehouse rather than from a manual chart review but that were included to confirm the patient’s identity during the chart review. BiRad: Breast Imaging Reporting and Data System; BMI, body mass index; N: no; Y: yes.…”

Section: Methodsmentioning

confidence: 99%

“…The use of risk assessment tools in the primary care setting has been shown to have moderate to high accuracy in guiding which patients should be referred to a cancer genetics professional, but the use of these tools requires additional time and effort to gather personal and family history information. 6 …”

Section: Introductionmentioning

confidence: 99%

Electronic health records contain dispersed risk factor information that could be used to prevent breast and ovarian cancer

Payne

Zhao

et al. 2020

Journal of the American Medical Informatics Association

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Objective The genetic testing for hereditary breast cancer that is most helpful in high-risk women is underused. Our objective was to quantify the risk factors for heritable breast and ovarian cancer contained in the electronic health record (EHR), to determine how many women meet national guidelines for referral to a cancer genetics professional but have no record of a referral. Methods and Materials We reviewed EHR records of a random sample of women to determine the presence and location of risk-factor information meeting National Comprehensive Cancer Network (NCCN) guidelines for a further genetic risk evaluation for breast and/or ovarian cancer, and determine whether the women were referred for such an evaluation. Results A thorough review of the EHR records of 299 women revealed that 24 (8%) met the NCCN criteria for referral for a further genetic risk evaluation; of these, 12 (50%) had no referral to a medical genetics clinic. Conclusions Half of the women whose EHR records contain risk-factor information meeting the criteria for further genetic risk evaluation for heritable forms of breast and ovarian cancer were not referred.

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“…Studies in populations with known founder mutations may detect mutations in 1.1–4.5% of individuals not selected based on a personal or family history of cancer [ 8 ]. Genetic testing based on family history approaches has a moderate to high diagnostic accuracy in predicting the detection of an inherited mutation, depending on the selected risk prediction tool [ 9 ]. Nevertheless, 50% of BRCA mutation carriers are missed through family history criteria [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis

et al. 2021

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Brazil is the largest country in South America and the most genetically heterogeneous. The aim of the present study was to determine the prevalence of germline pathogenic variants (PVs) in Brazilian patients with breast cancer (BC) who underwent genetic counseling and genetic testing at a tertiary Oncology Center. We performed a retrospective analysis of the medical records of Brazilian patients with BC referred to genetic counseling and genetic testing between August 2017 and August 2019. A total of 224 unrelated patients were included in this study. Premenopausal women represented 68.7% of the cohort. The median age at BC diagnosis was 45 years. Multigene panel testing was performed in 219 patients, five patients performed single gene analysis or family variant testing. Forty-eight germline PVs distributed among 13 genes were detected in 20.5% of the patients (46/224). Eighty-five percent of the patients (91/224) fulfilled NCCN hereditary BC testing criteria. Among these patients, 23.5% harbored PVs (45/191). In the group of patients that did not meet NCCN criteria, PV detection rate was 3% (1/33). A total of 61% of the patients (28/46) harbored a PV in a high-penetrance BC gene: 19 (8.5%) BRCA1/2, 8 (3.5%) TP53, 1 (0.5%) PALB2. Moderate penetrance genes (ATM, CHEK2) represented 15.2% (7/46) of the positive results. PVs detection was statistically associated (p<0.05) with BC diagnosis before age 45, high-grade tumors, bilateral BC, history of multiple primary cancers, and family history of pancreatic cancer. According to the current hereditary cancer guidelines, 17.4% (39/224) of the patients had actionable variants. Nine percent of the patients (20/224) had actionable variants in non-BRCA genes, it represented 43.5% of the positive results and 51.2% of the actionable variants. Considering the observed prevalence of PVs in actionable genes beyond BRCA1/2 (9%, 20/224), multigene panel testing may offer an effective first-tier diagnostic approach in this population.

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Risk Assessment, Genetic Counseling, and Genetic Testing forBRCA-Related Cancer in Women

Cited by 114 publications

References 169 publications

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Economic Evaluation of Population-Based BRCA1/BRCA2 Mutation Testing across Multiple Countries and Health Systems

Electronic health records contain dispersed risk factor information that could be used to prevent breast and ovarian cancer

Germline molecular data in hereditary breast cancer in Brazil: Lessons from a large single-center analysis

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