Current guidelines for BRCA testing of breast cancer patients are insufficient to detect all mutation carriers (original) (raw)
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Familial cancer, 2017
Increasing evidence supports the benefit of identifying BRCA1 and BRCA2 germline mutations in early breast cancer. Selection of patients for genetic testing is based on defined criteria taking individual and family history related factors into account. It is important to make a distinction between efficacy and effectiveness of BRCA testing criteria. Efficacy can be defined as the performance under ideal circumstances, whereas effectiveness refers to its real life performance. To allow for an unbiased and detailed evaluation of efficacy and effectiveness of the Swedish BRCA testing criteria, we retrospectively analyzed a prospectively collected cohort of 273 breast cancer patients from the well-characterized, population-based, single-site All Breast Cancer in Malmö (ABiM) study. The patients were diagnosed with breast cancer during the years 2007 through 2009. Out of 20 mutation carriers identified, 13 fulfilled Swedish criteria at time of diagnosis. Thus, the efficacy of these crite...
Utilization of BRCA1/BRCA2 Mutation Testing in Newly Diagnosed Breast Cancer Patients
Cancer Epidemiology Biomarkers & Prevention, 2005
Background: Among newly diagnosed breast cancer patients who are at risk for carrying a BRCA1 or BRCA2 mutation, knowledge of mutation status can influence local breast cancer treatment decisions. Thus, genetic testing at the time of diagnosis is increasingly considered an option for such patients. In this study, we evaluated factors associated with the decision to undergo BRCA1/BRCA2 gene testing at the time of initial breast cancer diagnosis. Methods: Participants were newly diagnosed breast cancer patients who had not yet received definitive local breast cancer treatment and who had a family history consistent with hereditary breast cancer. Participants were offered genetic counseling and BRCA1/BRCA2 testing with results in 2 to 3 weeks. Results: Of 231 patients who referred to the study, 20 (9%) declined the baseline interview, 34 (15%) completed a baseline interview but declined genetic testing, and 177 (76%) underwent BRCA1/BRCA2 testing. Physician recommendation for BRCA1/BRCA2 testing and indecision about definitive local treatment were both associated with undergoing testing. Among patients who were tested, 38 (21%) proceeded with definitive local treatment before receiving test results. Delay in the availability of test results and low levels of anxiety were associated with the decision to proceed with definitive local treatment before receiving test results. Conclusions: These results suggest that if rapid testing is available and genetic referrals are made for appropriate patients, a high proportion are likely to opt for such testing. In particular, patients who have not yet reached a decision about definitive local treatment may benefit from a genetic referral.
Journal of Medical Genetics, 2006
Background and objective: In clinical settings with fixed resources allocated to predictive genetic testing for high-risk cancer predisposition genes, optimal strategies for mutation screening programmes are critically important. These depend on the mutation spectrum found in the population under consideration and the frequency of mutations detected as a function of the personal and family history of cancer, which are both affected by the presence of founder mutations and demographic characteristics of the underlying population. The results of multistep genetic testing for mutations in BRCA1 or BRCA2 in a large series of families with breast cancer in the French-Canadian population of Quebec, Canada are reported. Methods: A total of 256 high-risk families were ascertained from regional familial cancer clinics throughout the province of Quebec. Initially, families were tested for a panel of specific mutations known to occur in this population. Families in which no mutation was identified were then comprehensively tested. Three algorithms to predict the presence of mutations were evaluated, including the prevalence tables provided by Myriad Genetics Laboratories, the Manchester Scoring System and a logistic regression approach based on the data from this study. Results: 8 of the 15 distinct mutations found in 62 BRCA1/BRCA2-positive families had never been previously reported in this population, whereas 82% carried 1 of the 4 mutations currently observed in >2 families. In the subset of 191 families in which at least 1 affected individual was tested, 29% carried a mutation. Of these 27 BRCA1-positive and 29 BRCA2-positive families, 48 (86%) were found to harbour a mutation detected by the initial test. Among the remaining 143 inconclusive families, all 8 families found to have a mutation after complete sequencing had Manchester Scores >18. The logistic regression and Manchester Scores provided equal predictive power, and both were significantly better than the Myriad Genetics Laboratories prevalence tables (p,0.001). A threshold of Manchester Score >18 provided an overall sensitivity of 86% and a specificity of 82%, with a positive predictive value of 66% in this population. Conclusion: In this population, a testing strategy with an initial test using a panel of reported recurrent mutations, followed by full sequencing in families with Manchester Scores >18, represents an efficient test in terms of overall cost and sensitivity.
Journal of the National Comprehensive Cancer Network : JNCCN, 2017
Background: Mutations in the BRCA1 and BRCA2 genes predispose individuals to a significantly elevated risk for breast and ovarian cancers. Identification of these individuals allows for proper screening, management, and testing of at-risk relatives. NCCN has established clinical criteria for recommending BRCA1/2 testing. Patients and Methods: A retrospective chart review of 1,123 patients with breast cancer was performed to evaluate the positive predictive values (PPVs) of 14 individual criteria for predicting BRCA1/2 mutations. Results: Two criteria had PPVs significantly below 10%. Only 2 of 115 patients who were recommended for testing based solely on the criterion of "diagnosed with breast cancer at ≤45 years of age" had pathogenic mutations at a PPV of 1.6% (95% CI, 0.2%-6.0%). Additionally, 0 of 37 individuals who underwent testing based on the criterion, "diagnosed with breast cancer at any age with ≥2 close blood relatives with breast cancer at any age" t...
Breast cancer research and treatment, 2017
BRCA mutations contribute to about 20% of all hereditary breast cancers. With full-genome sequencing as the emerging standard for genetic testing, other breast cancer susceptibility genes have been identified and may collectively contribute to up to 30% of all hereditary breast cancers. We re-assessed women who had previously tested negative for a BRCA mutation when outdated techniques were used, and discuss the implications of identifying a mutation several years after initial genetic testing. We evaluated the prevalence of mutations in 12 breast cancer susceptibility genes (including BRCA1 and BRCA2) in 190 breast cancer patients with a strong family history of breast cancer. These women had previously tested negative for mutations in the large coding exons of BRCA1 and BRCA2 using the protein truncation test (PTT) between the years of 1996 and 2013. We identified pathogenic mutations in 17 of 190 (9%) women. Six mutations were detected in BRCA1 (n = 2) and BRCA2 (n = 4). Eleven m...
The role of BRCA mutation testing in determining breast cancer therapy
2010
| Landmark discoveries in the field of breast cancer research include the identification of germline BRCA mutations as a cause of hereditary disease, and the use of gene-expression profiling to identify distinct subtypes of breast cancer. These findings, coupled with the availability of rapid germline testing, make it possible to identify a BRCA mutation carrier contemporaneous with a diagnosis of breast cancer. For the first time, testing for a germline mutation that predisposes to cancer has the potential to influence the immediate surgical, radiotherapeutic, and drug treatment choices of an individual with a new diagnosis of breast cancer. In this Review, we examine the implications of moving germline BRCA mutation testing from highly specialized family cancer clinics to mainstream settings.
ESMO Open
BackgroundIdentification of BRCA mutation carriers among patients with breast cancer (BC) involves costs and gains. Testing has been performed according to international guidelines, focusing on family history (FH) of breast and/or ovarian cancer. An alternative is testing all patients with BC employing sequencing of the BRCA genes and Multiplex Ligation Probe Amplification (MLPA).Patients and methodsA model-based cost-effectiveness analysis, employing data from Oslo University Hospital, Ullevål (OUH-U) and a decision tree, was done. The societal and the healthcare perspectives were focused and a lifetime perspective employed. The comparators were the traditional FH approach used as standard of care at OUH-U in 2013 and the intervention (testing all patients with BC) performed in 2014 and 2015 at the same hospital. During the latter period, 535 patients with BC were offered BRCA testing with sequencing and MLPA. National 2014 data on mortality rates and costs were implemented, a 3% d...
Future Oncology, 2022
Aim: We assessed real-world patient demographics and BRCA1/2 mutation testing rates among adult women with HER2-negative advanced breast cancer (ABC). Methods: Oncologists across the USA and in France, Germany, Italy, Spain and the UK provided medical chart data in 2015 and 2017. Results: Overall, 28% of patients received BRCA1/2 mutation testing. Untested patients were more likely to be aged ≥45 years, have hormone receptor-positive/HER2-negative ABC and have no known family history of breast/ovarian cancer. BRCA1/2 mutation testing rates were significantly lower in the European countries, women aged ≥45 years, women without a known family history of breast/ovarian cancer, and women with hormone receptor-positive/HER2-negative ABC versus advanced triple-negative breast cancer. Conclusion: BRCA1/2 mutation testing rates were low, and disparities were observed in patient characteristics among BRCA1/2 mutation-tested versus untested patients.
The Importance of a Family History of Breast Cancer in Predicting the Presence of a BRCA Mutation
The American Journal of Human Genetics, 1999
et al (1997) The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of earlyonset breast cancer patients among Ashkenazi women. Am J Hum Genet 60:505-514 Baker RJ, Nelder JA (1978) The GLIM system, release 3: generalized linear interactive modelling. Numerical Algorithms Group, Oxford Couch FJ, DeShano ML, Blackwood MA, Calzone K, Stopfer J, Campeau L, Ganguly A, et al (1997) BRCA1 mutation in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 336:1409-1415 Hartge P, Struewing JP, Wacholder S, Brody LC, Tucker, MA (1999) The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. Am J Hum Genet 64: 963-970 Hopper JL, Southey MC, Dite GS, Jolley DJ, Giles GG, McCredie MRE, Easton DF,and the Australian Breast Cancer Family Study (1999) Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Cancer Epidemiol Biomarker Prevent 8:741-747 McCullagh P, Nelder JA (1983) Generalized linear models. Easton DF, et al (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 91:943-949 Shattuck-Eidens D, Oliphant A, McClure M, McBride C, Gupte J, Rubano T, Pruss D, et al (1997) BRCA1 sequence analysis in women at high risk for susceptibility mutations: risk factor analysis and implications for genetic testing. JAMA 278:1242-1250 Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, et al (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336: