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PURPOSE: Germline CDH1 pathogenic variants (PV) are associated with hereditary diffuse gastric cancer and lobular breast cancer. Although prevalence of CDH1 PV is low in the general population, detection of these variants is increasing with the growing use of multigene panel testing. Little is known about the experiences of individuals tested for CDH1 variants in the multigene panel testing era. METHODS: Participants recruited from the Prospective Registry of Multiplex Testing completed a cross-sectional self-report survey regarding CDH1 genetic testing experiences, medical management, and psychosocial adaptation. RESULTS: Discordance existed in interpretations of CDH1 results; 13.3% of cases had disagreements in variant classifications among commercial laboratories, and 21.4% had disagreements between participant self-report and ClinVar classification. Survey data were available from 57 individuals reporting either PV (n = 16) or variants of uncertain significance (VUS; n = 41). Those with PV were more likely than those with VUS to report receiving a recommendation for prophylactic gastrectomy, although only 40.0% of those with PV received this recommendation. Participants with VUS were less satisfied with their health care providers' knowledge and reported less CDH1 knowledge, distress, and worry about discrimination. Participants with PV perceived greater breast cancer risks, but similar gastric cancer risks, as those with VUS. CONCLUSION: Few individuals with CDH1 PV report receiving recommendations for prophylactic gastrectomy, and no differences in perceived gastric cancer risk were observed based on participants' CDH1 results, suggesting serious unmet informational needs.
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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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Predisposição Genética para Doença/psicologia , Neoplasias/psicologia , Relações Pais-Filho , Pais/psicologia , Adulto , Criança , Revelação , Feminino , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Neoplasias/diagnóstico , Neoplasias/prevenção & controle , Fatores de Risco , Revelação da VerdadeRESUMO
PURPOSE: Identification of the 10% to 15% of patients with ovarian cancer who have germline BRCA1 or BRCA2 mutations is important for management of both patients and relatives. The BRCAPRO model, which estimates mutation likelihood based on personal and family cancer history, can inform genetic testing decisions. This study's purpose was to assess the accuracy of BRCAPRO in women with ovarian cancer. METHODS: BRCAPRO scores were calculated for 589 patients with ovarian cancer referred for genetic counseling at three institutions. Observed mutations were compared with those predicted by BRCAPRO. Analysis of variance was used to assess factors impacting BRCAPRO accuracy. RESULTS: One hundred eighty (31%) of 589 patients with ovarian cancer tested positive. At BRCAPRO scores less than 40%, more mutations were observed than expected (93 mutations observed v 34.1 mutations expected; P < .001). If patients with BRCAPRO scores less than 10% had not been tested, 51 (28%) of 180 mutations would have been missed. BRCAPRO underestimated the risk for high-grade serous ovarian cancers but overestimated the risk for other histologies (P < .001), underestimation increased as age at diagnosis decreased (P = .02), and model performance varied by institution (P = .02). CONCLUSION: Patients with ovarian cancer classified as low risk by BRCAPRO are more likely to test positive than predicted. The risk of a mutation in patients with low BRCAPRO scores is high enough to warrant genetic testing. This study demonstrates that assessment of family history by a validated model cannot effectively target testing to a high-risk ovarian cancer patient population, which strongly supports the recommendation to offer BRCA1/BRCA2 genetic testing to all patients with high-grade serous ovarian cancer regardless of family history.
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Cistadenocarcinoma Seroso/genética , Genes BRCA1 , Genes BRCA2 , Mutação em Linhagem Germinativa , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/patologia , Feminino , Predisposição Genética para Doença , Testes Genéticos , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Medição de Risco , Adulto JovemRESUMO
10-15% of invasive epithelial ovarian cancer is attributable to hereditary breast and ovarian cancer. The identification of BRCA1/BRCA2 mutations in women with ovarian cancer allows for accurate predictive genetic testing of their at-risk relatives, who can then avail themselves of early detection and risk reduction strategies. In the case of women with recurrent progressive ovarian cancer, the window of opportunity for genetic testing can be particularly limited. Here we describe our perspective on providing genetic counseling during these patients' end of life care, incorporating two illustrative examples from our clinical practice. While these situations pose unique challenges, they also present a significant opportunity to benefit the patient and her family. Further attention and research should be directed towards provision of genetic counseling and testing during end of life care.
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Aconselhamento Genético , Testes Genéticos , Recidiva Local de Neoplasia/genética , Neoplasias Ovarianas/genética , Assistência Terminal , Adulto , Feminino , Humanos , Neoplasias Ovarianas/terapiaRESUMO
Approximately 5-10% of cancers are caused by an inherited predisposition. Individuals affected by hereditary cancer are often concerned about transmitting a predisposition to cancer to their children. Preimplantation genetic diagnosis (PGD) is a technology that allows embryos without a deleterious mutation associated with a hereditary cancer syndrome to be identified and implanted. The aim of this study is to assess the knowledge, attitudes, and clinical experience of physicians regarding PGD for hereditary cancer predisposition syndromes. Hereditary Breast and Ovarian Cancer (HBOC) and Familial Adenomatous Polyposis (FAP) are two hereditary cancer syndromes highlighted in this present study. A survey assessing physicians' attitudes, knowledge, and clinical practice was completed by a total of 373 gynecologic oncologists (GYN ONCs) and obstetrics and gynecologists (OB/GYNs). Physicians had a limited knowledge of PGD for hereditary cancer; however, physicians reported PGD was an appropriate option for patients with either HBOC or FAP. Although GYN ONCs were more likely to care for patients with hereditary cancer (P < 0.001), they were less likely than OB/GYNs to refer their patients to a PGD specialist (P = 0.004). While 80% of GYN ONCs and 91% of OB/GYNs would refer patients to a PGD specialist, clinical experience indicates that only 29% actually referred their patients. Since 68% of physicians had incorrect or limited knowledge of PGD for hereditary cancer, there is a need for additional education.
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Predisposição Genética para Doença , Conhecimentos, Atitudes e Prática em Saúde , Síndromes Neoplásicas Hereditárias , Médicos/estatística & dados numéricos , Diagnóstico Pré-Implantação , Coleta de Dados , Feminino , Humanos , GravidezRESUMO
BACKGROUND: Cowden syndrome is an autosomal dominant disorder characterized by the development of multiple intestinal hamartomas, distinctive mucocutaneous lesions, and an increased risk of endometrial, breast, and thyroid cancer. CASE: An adolescent girl whose mother had a known germline PTEN mutation presented with abnormal vaginal bleeding and was diagnosed with a grade 2 endometrial adenocarcinoma. She underwent a robotic hysterectomy and was found to have no myometrial invasion or distant disease. Genetic testing revealed the patient to have the familial germline PTEN mutation. CONCLUSION: The strikingly young age of onset of this patient's endometrial cancer highlights the need for additional study to better understand Cowden syndrome and to determine what endometrial cancer screening and preventive strategies are needed.