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BACKGROUND: Implementing genetic testing for inherited cancer predisposition into routine clinical care offers a tremendous opportunity for cancer prevention and early detection. However, genetic testing itself does not improve outcomes; rather, outcomes depend on implemented follow-up care. The IMPACT study is a hybrid type I randomized effectiveness-implementation trial to simultaneously evaluate the effectiveness of two interventions for individuals with inherited cancer predisposition focused on: 1) increasing family communication (FC) of genetic test results; and 2) improving engagement with guideline-based cancer risk management (CRM). METHODS: This prospective study will recruit a racially, geographically, and socioeconomically diverse population of individuals with a documented pathogenic/likely pathogenic (P/LP) variant in an inherited cancer gene. Eligible participants will be asked to complete an initial trial survey and randomly assigned to one of three arms: A) GeneSHARE, a website designed to increase FC of genetic test results; B) My Gene Counsel's Living Lab Report, a digital tool designed to improve understanding of genetic test results and next steps, including CRM guidelines; or C) a control arm in which participants continue receiving standard care. Follow-up surveys will be conducted at 1, 3, and 12 months following randomization. These surveys include single-item measures, scales, and indices related to: 1) FC and CRM behaviors and behavioral factors following the COM-B theoretical framework (i.e., capability, opportunity, and motivation); 2) implementation outcomes (i.e., acceptability, appropriateness, exposure, and reach); and 3) other contextual factors (i.e., sociodemographic and clinical factors, and uncertainty, distress, and positive aspects of genetic test results). The primary outcomes are an increase in FC of genetic test results (Arm A) and improved engagement with guideline-based CRM without overtreatment or undertreatment (Arm B) by the 12-month follow-up survey. DISCUSSION: Our interventions are designed to shift the paradigm by which individuals with P/LP variants in inherited cancer genes are provided with information to enhance FC of genetic test results and engagement with guideline-based CRM. The information gathered through evaluating the effectiveness and implementation of these real-world approaches is needed to modify and scale up adaptive, stepped interventions that have the potential to maximize FC and CRM. TRIAL REGISTRATION: This study is registered at Clinicaltrials.gov (NCT04763915, date registered: February 21, 2021). PROTOCOL VERSION: September 17th, 2021 Amendment Number 04.
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Comunicación , Pruebas Genéticas , Neoplasias/diagnóstico , Neoplasias/genética , Revelación de la Verdad , Adulto , Detección Precoz del Cáncer/métodos , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Neoplasias/prevención & control , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/prevención & control , Estudios Prospectivos , RiesgoRESUMEN
The original article [1] was initially published with the following list of authors: Allison Werner-Lin, Shana L. Merrill, and Amanda C. Brandt. This author list is now corrected as follows: Allison Werner-Lin, Shana L. Merrill, Amanda C. Brandt, Rachel E. Barnett, & Ellen T. Matloff.
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Families often express difficulty to their providers and request guidance regarding the task of communicating with children about potential adult-onset inherited cancer risks. This disclosure is often complicated by the parent's ongoing adjustment to their mutation status, guilt at potential transmission of the mutation to the child, concern over inciting distress in children, and the varied capacities of children in the home to understand genetic information. Providers often do not have adequate resources to support or facilitate disclosure of genetic test results to children. Optimally, communication about inherited cancer risk is an open, ongoing process within the family. We recommend that parents tailor conversations to the child's developmental, cognitive, emotional, and behavioral abilities to support comprehension. Based on well-established theories of child development, empirical research on family communication of hereditary cancer risk, and clinical counseling experience, we offer recommendations for parental disclosure of genetic risk to children, case examples with critical discussion of relevant topics, common child questions with sample scripted responses, and additional printed and online resources.
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Predisposición Genética a la Enfermedad/psicología , Neoplasias/psicología , Relaciones Padres-Hijo , Padres/psicología , Adulto , Niño , Revelación , Femenino , Pruebas Genéticas/estadística & datos numéricos , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/prevención & control , Factores de Riesgo , Revelación de la VerdadRESUMEN
Next-generation sequencing promotes identification of mutations in non-BRCA1/2 genes in hereditary cancer families. The contribution of mutations in moderate penetrance genes to hereditary cancer risk is not well established. Here, we report a family with early onset breast and fallopian tube cancer that was identified as carrying germline mutations in BARD1 and ATM genes. Loss of heterozygosity studies suggest a causative role of the BARD1 mutation in the development of primary peritoneal cancer, but fail to confirm an association between germline ATM mutations and breast cancer development in this family. Complexities in interpreting implications of mutations in moderate-risk cancer susceptibility genes are discussed.
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Proteínas de la Ataxia Telangiectasia Mutada/genética , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad/genética , Neoplasias Ováricas/genética , Proteínas Supresoras de Tumor/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Mutación , LinajeRESUMEN
Hereditary mixed polyposis is a genetically heterogeneous, autosomal dominant condition with adenomatous, hyperplastic and juvenile polyps. We conducted a comprehensive clinical evaluation of a large Ashkenazi Jewish family with this phenotype and performed extensive genetic testing. As seen in one previous report, a 40 kb duplication upstream of GREM1 segregated with the polyposis/colon cancer phenotype in this kindred. Our study confirms the association of GREM1 with mixed polyposis and further defines the phenotype seen with this mutation. This gene should be included in the test panel for all Jewish patients with mixed polyposis and may be considered in any Ashkenazi patient with unexplained hereditary colon cancer when mutations in other hereditary colon cancer genes have been ruled out.
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Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/genética , Duplicación de Gen , Péptidos y Proteínas de Señalización Intercelular/genética , Adulto , Femenino , Asesoramiento Genético , Pruebas Genéticas , Humanos , Judíos , Masculino , Fenotipo , Adulto JovenRESUMEN
Approaches to hereditary breast cancer testing are shifting as multi-gene panels become more widely available. This paper describes our center's experience and outcomes of a 6-gene panel test as a first-tier approach in patients who were candidates for BRCA testing. Between July and December 2013, a 6-gene panel test was ordered for patients meeting criteria for BRCA testing. A retrospective review detailed the mutation and variant of uncertain significance (VUS) rates for the genes analyzed. The mutation rate was 5.2 % (n = 7) and the VUS rate was 6.7 % (n = 9). A subsequent review determined the number of BRCA-negative patients who would have been offered additional single gene testing had BRCA, only, been their first-tier test. Applying consensus criteria revealed 7.1 % (n = 9) cases that met criteria for additional testing. Pedigree analysis by a certified genetic counselor revealed 26.8 % (n = 34) cases that would have been offered additional testing based on personal and/or family history. Our results suggest that this panel may be warranted as a first-tier test for a small subset of patients, but likely represents over testing for the majority of patients who are candidates for BRCA testing. The genes selected for panels, the extra costs per patient and the chance of VUS must be considered before we uniformly switch from BRCA to full panel testing on all patients.
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Asesoramiento Genético/métodos , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas/métodos , Adulto , Proteína BRCA2/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Análisis Mutacional de ADN , Femenino , Variación Genética/genética , Humanos , Masculino , Estudios Retrospectivos , Ubiquitina-Proteína Ligasas/genéticaRESUMEN
Erratum to: J Genet Counsel DOI 10.1007/s10897-013-9625-z . In the "Funding" section, the company HRA was incorrectly referred to as HSR. The full name of the company is "HRA Healthcare Research & Analytics."
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Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan-Meier analyses. Use of RRSO was 45% for BRCA1 and 34% for BRCA2 by age 40, and 86% for BRCA1 and 71% for BRCA2 by age 50. RRM usage was estimated to be 46% by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de la Mama/cirugía , Mutación de Línea Germinal/genética , Mastectomía/mortalidad , Neoplasias Ováricas/cirugía , Ovariectomía/mortalidad , Conducta de Reducción del Riesgo , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Femenino , Estudios de Seguimiento , Heterocigoto , Humanos , Mastectomía/estadística & datos numéricos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/genética , Neoplasias Ováricas/mortalidad , Ovariectomía/estadística & datos numéricos , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
We surveyed cancer genetics specialists in 1998 to learn what they would do if at 50% risk to carry a BRCA or Lynch syndrome mutation. We chose to repeat our study 14 years later, to examine how perspectives have changed with the extensive data now available. In July 2012 we surveyed the National Society of Genetic Counselors (NSGC) Cancer Special Interest Group via an internet based survey. We found statistically significant increases in the percentage of specialists who: would undergo BRCA testing (p = 0.0006), opt for prophylactic bilateral mastectomy (p =0.0001), opt for prophylactic removal of their uterus and ovaries for Lynch syndrome (p =0.0057 and P = 0.0090, respectively), and bill testing to insurance (p >0.0001). There were also statistically significant decreases in the percentage of participants who would have their colon removed for Lynch syndrome (p = 0.0002) and use an alias when pursuing testing (p > 0.0001). Over the past 14 years there has been a major change in perspective amongst cancer genetic specialists regarding genetic testing, prophylactic surgery and insurance discrimination.
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Pruebas Genéticas , Cobertura del Seguro , Mastectomía/economía , Ovariectomía/economía , Prejuicio , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Femenino , Genes BRCA1 , Genes BRCA2 , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugíaRESUMEN
PURPOSE OF REVIEW: The field of cancer genetics and genetic testing is expanding rapidly. As our understanding of the hereditary nature of endocrine tumors increases, the role of genetic counseling on the multidisciplinary endocrinology team is becoming more critical. This brief review will highlight the role of the certified genetic counselor in this setting. RECENT FINDINGS: Genetic counseling and testing may aid in the management of the endocrine patient through early diagnosis and detection of disease, by optimizing surgical decision-making and improving overall survival. Certified genetic counselors assist the endocrinology team by eliciting a detailed pedigree, determining the appropriate genetic test to order, obtaining informed consent, interpreting complex genetic test results, providing psychosocial and family counseling, and assessing which family members are at risk. Many endocrine tumors can be caused by a variety of different genes and investment in the genetic counseling process likely increases the chance that the correct genetic test is ordered, results are interpreted accurately, and adequate informed consent and counseling is offered. SUMMARY: The field of endocrine genetics is growing exponentially and testing will likely play an even greater role in surveillance, medical management, and surgical decision-making in the next decade. Genetic counseling both pretesting and posttesting is essential to accurate, cost-efficient care for the endocrine patient and the entire family.
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Asesoramiento Genético , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico , Neoplasia Endocrina Múltiple Tipo 1/genética , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/genética , Endocrinología , Pruebas Genéticas , Humanos , LinajeRESUMEN
PURPOSE: In this ongoing case series, 33 genetic testing cases are documented in which tests were recommended, ordered, interpreted, or used incorrectly and/or in which clinicians faced challenges related to history/reports provided by patients or laboratories. METHODS: An invitation to submit cases of challenges or errors in genetic testing was issued to the general National Society of Genetic Counselors Listserv, the National Society of Genetic Counselors Cancer Special Interest Group members, as part of a case series with Precision Oncology News, and via social media (i.e., Facebook, Twitter, LinkedIn). Deidentified clinical documentation was requested and reviewed when available. Thirty-three cases were submitted, reviewed, and accepted. A thematic analysis was performed. Submitters were asked to approve cases before submission. RESULTS: All cases took place in the United States, involved hereditary cancer testing and/or findings in cancer predisposition genes, and involved medical-grade genetic testing, direct-to-consumer testing, or research genetic testing. In 9 cases, test results were misinterpreted, leading to incorrect screening or risk-reducing procedures being performed/recommended. In 5 cases, incorrect or unnecessary testing was ordered/recommended. In 3 cases, incorrect clinical diagnoses were made, or opportunities for diagnoses were delayed. In 3 cases, errors or challenges arose related to medical intervention after testing or reported genetic diagnosis. In 2 cases, physicians provided incorrect information related to the inheritance pattern of a syndrome. In 2 cases, there were challenges related to the interpretation of genetic variants. In 2 cases, challenges arose after direct-to-consumer testing. One case involved test results that should never have been reported based on sample quality. In 1 case, a patient presented a falsified test result. In 5 cases, multiple errors were made. DISCUSSION: As genetic testing continues to become more complicated and common, it is critical that patients and nongenetics providers have access to accurate and timely genetic counseling information. Even as multiple medical bodies highlight the value of genetic counselors (GCs), tension exists in the genomics community as GCs work toward licensure and Medicare provider status. It is critical that health care communities leverage, rather than restrict, the expertise and experience of GCs so that patients can benefit from, and not be harmed by, genetic testing. In order to responsibly democratize genomics, it will be important for genetics and nongenetic health care providers to collaborate and use alternative service delivery models and technology solutions at point of care. To deliver on the promise of precision medicine, accurate resources and tools must be utilized.
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Neoplasias , Anciano , Asesoramiento Genético , Pruebas Genéticas , Humanos , Medicare , Neoplasias/diagnóstico , Neoplasias/genética , Medicina de Precisión , Estados UnidosRESUMEN
Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in BRCA1 or BRCA2 (BRCA1/2) mutation carriers. Occult ovarian/fallopian tube cancers (OOC) detected at the time of RRSO have been reported in several studies with wide variability in reported prevalence. We estimated the prevalence of OOC in a prospective cohort of 647 BRCA1/2 mutation carriers from 18 centers (PROSE consortium) who underwent RRSO between 2001 and 2008. OOC was detected in 16 of 647 women (2.5%). The mean age at RRSO was 51.7 in those with OOC versus 46.6 in those without OOC (P = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with BRCA1 mutations. Thirty-eight percent of women with OOC had stage 1 cancer versus none of the women in the PROSE database diagnosed with ovarian cancer outside of screening. Among 385 women (60%) in whom pathology reports were available for central review, 246 (64%) RRSOs were performed at participating PROSE centers while 139 (36%) were performed at local sites. Ovarian and fallopian tube tissues removed at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at non-referral centers (75% vs. 30%, P < 0.001). Our results confirm that OOC may be found at the time of RRSO in BRCA1/2 mutation carriers and suggest that OOC are of a more favorable stage than cancers found outside RRSO. An unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO.
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Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias de las Trompas Uterinas/prevención & control , Mutación , Neoplasias Ováricas/prevención & control , Ovariectomía , Prevención Primaria/métodos , Adulto , Anciano , Europa (Continente) , Neoplasias de las Trompas Uterinas/diagnóstico , Neoplasias de las Trompas Uterinas/epidemiología , Neoplasias de las Trompas Uterinas/genética , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , América del Norte , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Conducta de Reducción del RiesgoRESUMEN
CONTEXT: Mastectomy and salpingo-oophorectomy are widely used by carriers of BRCA1 or BRCA2 mutations to reduce their risks of breast and ovarian cancer. OBJECTIVE: To estimate risk and mortality reduction stratified by mutation and prior cancer status. DESIGN, SETTING, AND PARTICIPANTS: Prospective, multicenter cohort study of 2482 women with BRCA1 or BRCA2 mutations ascertained between 1974 and 2008. The study was conducted at 22 clinical and research genetics centers in Europe and North America to assess the relationship of risk-reducing mastectomy or salpingo-oophorectomy with cancer outcomes. The women were followed up until the end of 2009. MAIN OUTCOMES MEASURES: Breast and ovarian cancer risk, cancer-specific mortality, and overall mortality. RESULTS: No breast cancers were diagnosed in the 247 women with risk-reducing mastectomy compared with 98 women of 1372 diagnosed with breast cancer who did not have risk-reducing mastectomy. Compared with women who did not undergo risk-reducing salpingo-oophorectomy, women who underwent salpingo-oophorectomy had a lower risk of ovarian cancer, including those with prior breast cancer (6% vs 1%, respectively; hazard ratio [HR], 0.14; 95% confidence interval [CI], 0.04-0.59) and those without prior breast cancer (6% vs 2%; HR, 0.28 [95% CI, 0.12-0.69]), and a lower risk of first diagnosis of breast cancer in BRCA1 mutation carriers (20% vs 14%; HR, 0.63 [95% CI, 0.41-0.96]) and BRCA2 mutation carriers (23% vs 7%; HR, 0.36 [95% CI, 0.16-0.82]). Compared with women who did not undergo risk-reducing salpingo-oophorectomy, undergoing salpingo-oophorectomy was associated with lower all-cause mortality (10% vs 3%; HR, 0.40 [95% CI, 0.26-0.61]), breast cancer-specific mortality (6% vs 2%; HR, 0.44 [95% CI, 0.26-0.76]), and ovarian cancer-specific mortality (3% vs 0.4%; HR, 0.21 [95% CI, 0.06-0.80]). CONCLUSIONS: Among a cohort of women with BRCA1 and BRCA2 mutations, the use of risk-reducing mastectomy was associated with a lower risk of breast cancer; risk-reducing salpingo-oophorectomy was associated with a lower risk of ovarian cancer, first diagnosis of breast cancer, all-cause mortality, breast cancer-specific mortality, and ovarian cancer-specific mortality.
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Neoplasias de la Mama/mortalidad , Genes BRCA1 , Genes BRCA2 , Mastectomía , Neoplasias Ováricas/mortalidad , Ovariectomía , Adolescente , Adulto , Anciano , Neoplasias de la Mama/genética , Neoplasias de la Mama/prevención & control , Causas de Muerte , Trompas Uterinas/cirugía , Femenino , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Persona de Mediana Edad , Mutación , Neoplasias Ováricas/genética , Neoplasias Ováricas/prevención & control , Estudios Prospectivos , RiesgoRESUMEN
UNLABELLED: Advances in genetics have prompted recommendations that all healthcare providers perform genetic counseling and testing. Some experts are concerned about potential negative outcomes from cancer genetic testing performed without genetic counseling by certified genetics professionals. We report a national series of cases illustrating negative outcomes of cancer genetic testing performed without counseling by a qualified provider. Three major patterns emerged from analysis of these cases: 1) Wrong genetic test ordered, 2) Genetic test results misinterpreted, and 3) Inadequate genetic counseling. Negative outcomes included unnecessary prophylactic surgeries, unnecessary testing, psychosocial distress, and false reassurance resulting in inappropriate medical management. CONCLUSION: With the complexities of cancer genetic counseling and testing, it may be unrealistic to expect all clinicians to provide these services. A more realistic approach is better provider education and a framework in which healthcare providers identify patients who would benefit from a referral to a certified genetic counselor or experienced cancer genetics professional.
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Errores Diagnósticos , Genes Relacionados con las Neoplasias/genética , Asesoramiento Genético/normas , Pruebas Genéticas/normas , Femenino , Humanos , MasculinoAsunto(s)
Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Inestabilidad de Microsatélites , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Reparación de la Incompatibilidad de ADN , Reforma de la Atención de Salud , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa , PronósticoRESUMEN
PURPOSE: In this ongoing national case series, we document 25 new genetic testing cases in which tests were recommended, ordered, interpreted, or used incorrectly. METHODS: An invitation to submit cases of adverse events in genetic testing was issued to the general National Society of Genetic Counselors Listserv, the National Society of Genetic Counselors Cancer Special Interest Group members, private genetic counselor laboratory groups, and via social media platforms (i.e., Facebook, Twitter, LinkedIn). Examples highlighted in the invitation included errors in ordering, counseling, and/or interpretation of genetic testing and did not limit submissions to cases involving genetic testing for hereditary cancer predisposition. Clinical documentation, including pedigree, was requested. Twenty-six cases were accepted, and a thematic analysis was performed. Submitters were asked to approve the representation of their cases before manuscript submission. RESULTS: All submitted cases took place in the United States and were from cancer, pediatric, preconception, and general adult settings and involved both medical-grade and direct-to-consumer genetic testing with raw data analysis. In 8 cases, providers ordered the wrong genetic test. In 2 cases, multiple errors were made when genetic testing was ordered. In 3 cases, patients received incorrect information from providers because genetic test results were misinterpreted or because of limitations in the provider's knowledge of genetics. In 3 cases, pathogenic genetic variants identified were incorrectly assumed to completely explain the suspicious family histories of cancer. In 2 cases, patients received inadequate or no information with respect to genetic test results. In 2 cases, result interpretation/documentation by the testing laboratories was erroneous. In 2 cases, genetic counselors reinterpreted the results of people who had undergone direct-to-consumer genetic testing and/or clarifying medical-grade testing was ordered. DISCUSSION: As genetic testing continues to become more common and complex, it is clear that we must ensure that appropriate testing is ordered and that results are interpreted and used correctly. Access to certified genetic counselors continues to be an issue for some because of workforce limitations. Potential solutions involve action on multiple fronts: new genetic counseling delivery models, expanding the genetic counseling workforce, improving genetics and genomics education of nongenetics health care professionals, addressing health care policy barriers, and more. Genetic counselors have also positioned themselves in new roles to help patients and consumers as well as health care providers, systems, and payers adapt to new genetic testing technologies and models. The work to be done is significant, but so are the consequences of errors in genetic testing.
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Pruebas Genéticas/normas , Errores Diagnósticos , Asesoramiento Genético/métodos , Asesoramiento Genético/normas , Pruebas Genéticas/métodos , Humanos , Errores Médicos , Uso Excesivo de los Servicios de Salud , Estados UnidosRESUMEN
Myriad Genetics holds a patent on testing for the hereditary breast and ovarian cancer genes, BRCA1 and BRCA2, and therefore has a forced monopoly on this critical genetic test. Myriad launched a Direct-to-Consumer (DTC) marketing campaign in the Northeast United States in September 2007 and plans to expand that campaign to Florida and Texas in 2008. The ethics of Myriad's patent, forced monopoly and DTC campaign will be reviewed, as well as the impact of this situation on patient access and care, physician liability, and the future of DTC campaigns for genetic testing.
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Biotecnología/ética , Neoplasias de la Mama/prevención & control , Genes BRCA1 , Genes BRCA2 , Pruebas Genéticas/ética , Comercialización de los Servicios de Salud/ética , Neoplasias Ováricas/prevención & control , Sector Privado/ética , Mercadeo Social/ética , Neoplasias de la Mama/genética , Femenino , Asesoramiento Genético/ética , Predisposición Genética a la Enfermedad , Pruebas Genéticas/economía , Accesibilidad a los Servicios de Salud , Humanos , Responsabilidad Legal , Neoplasias Ováricas/genética , Patentes como Asunto/ética , Salud Pública/ética , Estados UnidosRESUMEN
BACKGROUND: Data concerning the efficacy of bilateral prophylactic oophorectomy for reducing the risk of gynecologic cancer in women with BRCA1 or BRCA2 mutations are limited. We investigated whether this procedure reduces the risk of cancers of the coelomic epithelium and breast in women who carry such mutations. METHODS: A total of 551 women with disease-associated germ-line BRCA1 or BRCA2 mutations were identified from registries and studied for the occurrence of ovarian and breast cancer. We determined the incidence of ovarian cancer in 259 women who had undergone bilateral prophylactic oophorectomy and in 292 matched controls who had not undergone the procedure. In a subgroup of 241 women with no history of breast cancer or prophylactic mastectomy, the incidence of breast cancer was determined in 99 women who had undergone bilateral prophylactic oophorectomy and in 142 matched controls. The length of postoperative follow-up for both groups was at least eight years. RESULTS: Six women who underwent prophylactic oophorectomy (2.3 percent) received a diagnosis of stage I ovarian cancer at the time of the procedure; two women (0.8 percent) received a diagnosis of papillary serous peritoneal carcinoma 3.8 and 8.6 years after bilateral prophylactic oophorectomy. Among the controls, 58 women (19.9 percent) received a diagnosis of ovarian cancer, after a mean follow-up of 8.8 years. With the exclusion of the six women whose cancer was diagnosed at surgery, prophylactic oophorectomy significantly reduced the risk of coelomic epithelial cancer (hazard ratio, 0.04; 95 percent confidence interval, 0.01 to 0.16). Of 99 women who underwent bilateral prophylactic oophorectomy and who were studied to determine the risk of breast cancer, breast cancer developed in 21 (21.2 percent), as compared with 60 (42.3 percent) in the control group (hazard ratio, 0.47; 95 percent confidence interval, 0.29 to 0.77). CONCLUSIONS: Bilateral prophylactic oophorectomy reduces the risk of coelomic epithelial cancer and breast cancer in women with BRCA1 or BRCA2 mutations.
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Neoplasias de la Mama/prevención & control , Genes BRCA1 , Genes BRCA2 , Neoplasias Ováricas/prevención & control , Ovariectomía , Neoplasias Peritoneales/prevención & control , Adulto , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/genética , Estudios de Casos y Controles , Cistadenocarcinoma Seroso/epidemiología , Femenino , Mutación de Línea Germinal , Humanos , Incidencia , Persona de Mediana Edad , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Peritoneales/epidemiología , Neoplasias Peritoneales/genética , Modelos de Riesgos Proporcionales , RiesgoRESUMEN
BACKGROUND: Women with BRCA1 or BRCA2 (BRCA1/2) mutations can reduce cancer incidence and mortality by using bilateral prophylactic oophorectomy (BPO) or bilateral prophylactic mastectomy (BPM). The availability of these risk-reduction strategies is an important consideration in the decision to undergo genetic testing. PATIENTS AND METHODS: We evaluated the use of BPO and BPM in a prospective sample of 537 female BRCA1/2 mutation carriers from 17 centers in North America and Europe. These women were aged > 30 years, had no BPM, BPO, breast cancer, or ovarian cancer before the disclosure of their genetic test results and were followed for > or = 6 months. RESULTS: Bilateral prophylactic oophorectomy is used significantly more frequently than BPM (55% vs. 21%; P < .001). Bilateral prophylactic oophorectomy was more common among women age > or = 40 years compared with women aged < 40 years (68% vs. 43%; P < .001) and among parous women compared with nulliparous women (60% vs. 39%; P < .001). There was no difference in BPM (P = .83) or BPO (P = .09) in BRCA1 versus BRCA2 carriers. Multivariate models identified age and parity as a predictor of BPO in BRCA1 carriers; age and ovarian cancer family history in BRCA2 carriers; parity and ovarian cancer family history as a predictor of BPM in BRCA1 carriers; and smoking and ovarian cancer family history in BRCA2 carriers. CONCLUSION: Bilateral prophylactic oophorectomy is more commonly used than BPM in unaffected BRCA1/2 mutation carriers. Parity, age, and family history can also influence BPO and BPM uptake. Consistent with current recommendations, BPO is used by the majority of parous women aged > 40 years.