RESUMEN
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.
Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Masculino , Femenino , Humanos , Mutación de Línea Germinal , Pruebas Genéticas , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Factores de Riesgo , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genéticaRESUMEN
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic or likely pathogenic variants associated with increased risk of breast, ovarian, and pancreatic cancer and recommended approaches to genetic testing/counseling and management strategies in individuals with these pathogenic or likely pathogenic variants. This manuscript focuses on cancer risk and risk management for BRCA-related breast/ovarian cancer syndrome and Li-Fraumeni syndrome. Carriers of a BRCA1/2 pathogenic or likely pathogenic variant have an excessive risk for both breast and ovarian cancer that warrants consideration of more intensive screening and preventive strategies. There is also evidence that risks of prostate cancer and pancreatic cancer are elevated in these carriers. Li-Fraumeni syndrome is a highly penetrant cancer syndrome associated with a high lifetime risk for cancer, including soft tissue sarcomas, osteosarcomas, premenopausal breast cancer, colon cancer, gastric cancer, adrenocortical carcinoma, and brain tumors.
Asunto(s)
Neoplasias de la Mama , Neoplasias Ováricas , Neoplasias Pancreáticas , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Femenino , Genes BRCA1 , Genes BRCA2 , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Masculino , Mutación , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genéticaRESUMEN
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic provide recommendations for genetic testing and counseling for hereditary cancer syndromes, and risk management recommendations for patients who are diagnosed with syndromes associated with an increased risk of these cancers. The NCCN panel meets at least annually to review comments, examine relevant new data, and reevaluate and update recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding criteria for high-penetrance genes associated with breast and ovarian cancer beyond BRCA1/2, pancreas screening and genes associated with pancreatic cancer, genetic testing for the purpose of systemic therapy decision-making, and testing for people with Ashkenazi Jewish ancestry.
Asunto(s)
Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biomarcadores de Tumor , Femenino , Estudios de Asociación Genética , Asesoramiento Genético , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Humanos , Síndromes Neoplásicos Hereditarios/terapia , Penetrancia , Neoplasias PancreáticasRESUMEN
The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer.
Asunto(s)
Asesoramiento Genético/normas , Pruebas Genéticas/normas , Síndrome de Cáncer de Mama y Ovario Hereditario/diagnóstico , Síndrome de Cáncer de Mama y Ovario Hereditario/genética , Femenino , Humanos , Mutación , Guías de Práctica Clínica como Asunto , Medición de Riesgo/normas , Factores de RiesgoRESUMEN
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling and risk assessment and management for hereditary cancer syndromes. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer and are intended to assist with clinical and shared decision-making. These NCCN Guidelines Insights summarize major discussion points of the 2015 NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meeting. Major discussion topics this year included multigene testing, risk management recommendations for less common genetic mutations, and salpingectomy for ovarian cancer risk reduction. The panel also discussed revisions to genetic testing criteria that take into account ovarian cancer histology and personal history of pancreatic cancer.
Asunto(s)
Neoplasias de la Mama/genética , Neoplasias Ováricas/genética , Femenino , Asesoramiento Genético/métodos , Predisposición Genética a la Enfermedad/genética , Pruebas Genéticas/métodos , Humanos , Mutación/genética , Síndromes Neoplásicos Hereditarios/genética , Neoplasias Pancreáticas/genética , Medición de Riesgo/métodos , Factores de RiesgoRESUMEN
During the past few years, several genetic aberrations that may contribute to increased risks for development of breast and/or ovarian cancers have been identified. The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian focus specifically on the assessment of genetic mutations in BRCA1/BRCA2, TP53, and PTEN, and recommend approaches to genetic testing/counseling and management strategies in individuals with these mutations. This portion of the NCCN Guidelines includes recommendations regarding diagnostic criteria and management of patients with Cowden Syndrome/PTEN hamartoma tumor syndrome.
Asunto(s)
Síndrome de Hamartoma Múltiple/diagnóstico , Síndrome de Hamartoma Múltiple/genética , Manejo de la Enfermedad , Femenino , Asesoramiento Genético , Pruebas Genéticas , Mutación de Línea Germinal , Humanos , MasculinoRESUMEN
Women in the United States have a 12% lifetime risk of developing breast cancer. Although only about 5% to 10% of all cases of breast cancer are attributable to a highly penetrant cancer predisposition gene, individuals who carry a mutation in one of these genes have a significantly higher risk of developing breast cancer, as well as other cancers, over their lifetime compared with the general population. The ability to distinguish those individuals at high risk allows health care providers to intervene with appropriate counseling and education, surveillance, and prevention-with the overall goal of improved survival for these individuals. This article focuses on the identification of patients at high risk for breast cancer and provides an overview of the clinical features, cancer risks, causative genes, and medical management for the most clearly described hereditary breast cancer syndromes. Newer genes that have also been implicated in familial breast cancer are also briefly reviewed.
Asunto(s)
Neoplasias de la Mama Masculina/genética , Neoplasias de la Mama/genética , Predisposición Genética a la Enfermedad , Pruebas Genéticas , Síndromes Neoplásicos Hereditarios/genética , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama Masculina/diagnóstico , Femenino , Genes BRCA1 , Genes BRCA2 , Genes p53 , Asesoramiento Genético , Humanos , Masculino , Síndromes Neoplásicos Hereditarios/diagnóstico , Medición de RiesgoRESUMEN
PURPOSE: Individuals undergoing genetic testing for BRCA1/2 mutations are routinely counseled about the sensitivity and specificity of testing. In August 2002, testing for 5 large genomic rearrangements in the BRCA1 gene that would not have been detected with full gene sequence analysis became commercially available. We present our data on uptake of the BRCA1 rearrangement panel testing in our clinical cancer genetics program. METHODS: Women who participated in our clinical genetic testing program and had previously received an uninformative negative or variant of uncertain significance result from BRCA1/2 full gene sequencing were invited to consider BRCA1 rearrangement panel testing. RESULTS: Overall, 18/72 individuals underwent BRCA1 rearrangement panel testing. No significant differences were found in the levels of BRCAPRO scores (P = 0.406), age at testing (P = 0.986), number of children (P = 0.35) or number of siblings (P = 0.4) between individuals who chose to pursue additional testing with the rearrangement panel and those who declined. Fisher's Exact Test analysis showed that there is a negative association between having breast or ovarian cancer and being inclined to undergo rearrangement panel testing (P = 0.013). CONCLUSION: Individuals who undergo genetic testing will not consistently pursue additional or enhanced genetic testing. Future research is needed to clearly elucidate the factors associated with uptake of additional genetic testing.