Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study.

IMPORTANCE: BRCA genetic testing has substantial public health impact, yet little is known of the real-world experiences of the more than 100 000 Americans undergoing testing annually. OBJECTIVE: To identify factors associated with use of BRCA testing, assess whether delivery of genetic counseling and testing services adheres to professional guidelines, and measure the impact on patient-reported outcomes. DESIGN, SETTING, AND PARTICIPANTS: The American BRCA Outcomes and Utilization of Testing (ABOUT) Study analyzed data from a consecutive national series of 11 159 women whose clinicians ordered BRCA testing between December 2011 and December 2012. Aetna mailed recruitment information across the United States to commercial health plan members whose clinicians had ordered BRCA testing. A total of 3874 women (34.7%) completed questionnaires. Deidentified clinician-reported data from all respondents and a random sample of 2613 nonrespondents were also analyzed. MAIN OUTCOMES AND MEASURES: The proportion of eligible participants who met testing criteria and respondents' report of receiving genetic counseling by a genetics clinician and its association with BRCA knowledge, understanding, and satisfaction were assessed. RESULTS: Among 3628 women respondents whose clinicians ordered comprehensive BRCA testing, most were white non-Hispanic (2502 [69.0%]), college educated (2953 [81.4%]), married (2751 [75.8%]), and had higher incomes (2011 [55.4%]). Approximately 16.4% (596) did not meet testing criteria. Mutations were identified in 161 (5.3%) of these women who received comprehensive testing. Only 1334 (36.8%) reported receiving genetic counseling from a genetics clinician prior to testing; the lowest rates (130 [12.3%]) were among patients of obstetrician/gynecologists. The most commonly reported reason for not receiving this clinical service was lack of clinician recommendation. Those who received it demonstrated greater knowledge about BRCA (mean score difference adjusted for demographics and clinician specialty, ß = 0.99 [95% CI, 0.83-1.14]; P < .001) and expressed greater understanding (ß = 0.47 [95% CI, 0.41-0.54]; P < .001) and satisfaction (ß = 2.21 [95% CI, 1.60-2.81]; P < .001). CONCLUSIONS AND RELEVANCE: Despite improved patient knowledge, understanding, and satisfaction among patients who receive genetic counseling provided by a genetics clinician, as well as multiple guidelines emphasizing the importance of genetic counseling, most US women undergoing BRCA genetic testing do not receive this clinical service. Lack of physician recommendation is the most commonly reported reason. These findings demonstrate important gaps in clinical genetics services. Recently mandated coverage of genetic counseling services as a preventive service without patient cost sharing should contribute to improving clinical genetics services and associated outcomes in the future.

Risk and risk assessment for breast cancer: molecular and clinical aspects.

Chemoprevention, prophylactic surgery and intensified screening programs are options which can be offered the patients with an increased lifetime risk (p(life)) for breast cancer (BC). Estimation of p(life) includes BRCA mutation analysis and risk estimation based on individual risk factors and family history. MENDEL and BRCAPRO are models which can estimate mutation carrier status probability (p(mut)), p(life) and p(mut) can be estimated using Cyrillic3 software which incorporates BRCAPRO and MENDEL. To integrate age, hormonal factors and benign breast biopsies in risk assessment the Tyrer-Cuzick model can be used. These models support the decision pro or contra genetic analysis and improve the number of positive gene testing results. Estimations of p(life) and p(mut), based on a mathematical model, should deal with algorithms and penetrance/frequency data adequate to the population counselled. Being the main modulatory factors, reproductive/hormonal data should be incorporated like the Tyrer-Cuzick model does.

Natural history of Ashkenazi intelligence.

This paper elaborates the hypothesis that the unique demography and sociology of Ashkenazim in medieval Europe selected for intelligence. Ashkenazi literacy, economic specialization, and closure to inward gene flow led to a social environment in which there was high fitness payoff to intelligence, specifically verbal and mathematical intelligence but not spatial ability. As with any regime of strong directional selection on a quantitative trait, genetic variants that were otherwise fitness reducing rose in frequency. In particular we propose that the well-known clusters of Ashkenazi genetic diseases, the sphingolipid cluster and the DNA repair cluster in particular, increase intelligence in heterozygotes. Other Ashkenazi disorders are known to increase intelligence. Although these disorders have been attributed to a bottleneck in Ashkenazi history and consequent genetic drift, there is no evidence of any bottleneck. Gene frequencies at a large number of autosomal loci show that if there was a bottleneck then subsequent gene flow from Europeans must have been very large, obliterating the effects of any bottleneck. The clustering of the disorders in only a few pathways and the presence at elevated frequency of more than one deleterious allele at many of them could not have been produced by drift. Instead these are signatures of strong and recent natural selection.

Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: a naturally-occurring experiment.

PURPOSE: To describe the impact of Myriad Genetics, Inc.'s direct-to-consumer advertising (DTC-ad) campaign on cancer genetic services within two Managed Care Organizations, Kaiser Permanente Colorado (KPCO), Denver, Colorado, where the ad campaign occurred, and Henry Ford Health System (HFHS), Detroit, Michigan, where there were no advertisements. METHODS: The main outcome measures were the changes in number and pretest mutation probability of referrals approved for cancer genetic services at KPCO and HFHS during the campaign versus the year prior, and mutation probability of those undergoing testing. RESULTS: At KPCO, referrals increased 244% during the DTC-ad compared to the same time period a year earlier (P value<0.001). The proportion of referrals at high pretest probability of a mutation (10% or greater) dropped from 69% the previous year to 48% during the campaign (P value<0.001). There was no significant change in pretest mutation probability among women who underwent testing between the two time periods. HFHS reported no significant change between the two time periods for numbers or mutation probability of referrals, or for mutation probability of women tested. CONCLUSION: The DTC-ad caused significant increase in demand for cancer genetic services. In the face of potential future DTC-ad for inherited cancer risk, providers and payers need to consider the delivery of genetic services and genetic education for persons of all risk levels.

Breast and ovarian cancer genetics and prevention.

Inherited breast and ovarian cancers account for 10% of all breast and ovarian cancers. Relative to sporadic breast and ovarian cancers, these cancers tend to occur at an earlier age and grow more aggressively. Women with BRCA1 and BRCA2 mutations (BRCA1/2 mutation) have a 65% to 85% cumulative lifetime risk of developing invasive breast cancer and a 15% to 65% cumulative lifetime risk of developing invasive ovarian cancer. Identification of patients with the mutation is therefore crucial, because preventive measures such as prophylactic bilateral mastectomy, prophylactic bilateral salpingpo-oophorectomy and chemoprevention with Tamoxifen can prevent breast and ovarian cancer. Likewise, genetic counseling prior to testing is important, considering the major impact of the test results on an individual's life.

Testing for the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes: a decision analysis.

OBJECTIVE: The authors developed a Markov decision model to evaluate the health implications of testing for mutations in the BRCA1 and BRCA2 breast-ovarian cancer susceptibility genes. Prophylactic measures considered included various combinations of immediate and delayed bilateral mastectomy and oophorectomy or taking no action. METHODS: The model incorporated the likelihood of developing breast and/or ovarian cancer, survival, and quality of life. Parameter values were taken from public databases, the published literature, and a survey of cancer experts. Outcomes considered were additional life expectancy and quality-adjusted life years (QALYs). Results are reported for 30-year-old cancer-free women at various levels of hereditary risk. RESULTS AND CONCLUSIONS: The vast majority of women will not benefit from testing because their pre-test risks are low and surgical prophylaxis is undesirable. However, women who have family histories of early breast and/or ovarian cancer may gain up to 2 QALYs by allowing genetic testing to inform their decisions.