Expanding the phenotype of E318K (c.952G > A) MITF germline mutation carriers: case series and review of the literature.

BACKGROUND: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma. CASE PRESENTATION: We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives. CONCLUSIONS: Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.

Double heterozygous pathogenic variants prevalence in a cohort of patients with hereditary breast cancer.

Hereditary breast cancer (BC) corresponds to 5% of all BC and a larger parcel of early-onset disease. The incorporation of next-generation sequencing (NGS) techniques reduced the cost of molecular testing and allowed the inclusion of additional cancer predisposition genes in panels that are more comprehensive. This enabled the identification of germline pathogenic variants in carriers and the introduction of risk-reducing strategies. It also resulted in the identification of the co-occurrence of more than one germline pathogenic variant in BC genes in some families. This is a rare event, and there are few reports on its impact on cancer risk. We conducted a single-institution retrospective study in which 1,156 women with early onset BC and/or a family history of cancer were tested by a germline multi-gene hereditary cancer panel. Germline pathogenic variants in high- and/or moderate-penetrance BC genes were identified in 19.5% of the individuals (n = 226). The most frequent variants were found in TP53 (69 of 226; 55 of them represented by p.R337H), BRCA1 (47 of 226), and BRCA2 (41 of 226). Double heterozygous (DH) variants were detected in 14 cases, representing 1.2% of all individuals assessed. There were no significant differences in age of BC onset and risk for bilateral BC in DH carriers when compared with those with one germline variant.

Breast Cancer Phenotype Associated With Li-Fraumeni Syndrome: A Brazilian Cohort Enriched by TP53 p.R337H Carriers.

Breast cancer (BC) is the most prevalent malignancy in women with Li-Fraumeni syndrome (LFS). The literature on BC in LFS is limited due to its rarity worldwide. A TP53 founder pathogenic variant (c.1010G>A; p.R337H) is responsible for the higher prevalence of this syndrome among women of Brazilian ancestry. Purpose: The aim of the study was to describe the BC phenotype expressed by Brazilian female LFS carriers and compare the data between p.R337H and other TP53 germline pathogenic/likely pathogenic variants (non-p.R337H carriers). Methods: We searched for cases of TP53 germline pathogenic/likely pathogenic variant carriers affected by BC included between 2015 and 2020 in the BLiSS (Brazilian Li-Fraumeni Study) registry at the Sírio-Libanês Hospital. Results: Among 163 adult female carriers from the registry, 91 (56%) had received a BC diagnosis, including 72 p.R337H carriers. BC was the first cancer diagnosed in 90% of cases. Early onset BC (age ≤45 years) was diagnosed in 78.2% of cases (11.5% <31 years; 66.7% 31-45 years; 21.8% >45 years). The median age of BC diagnosis for p.R337H carriers was 39.5 years (range 20-69 years) compared to 34 years (range 21-63 years) for non-p.R337H carriers (p = 0.009). In total, 104 breast tumors were observed in 87 women. Bilateral BC was observed in 29.3% of cases. Histology was available for 96 tumors, comprising 69 invasive breast carcinomas, which were mostly invasive ductal carcinomas (95.6%), 25 ductal in situ carcinomas and 2 soft-tissue sarcomas. Overall, 90.5% of invasive breast carcinomas were hormone receptor (HR)-positive, 39.5% were human epidermal growth factor receptor 2 (HER2)-positive, and 32.8% showed HR and HER2 co-expression. In addition, 55.4% of patients opted for contralateral prophylactic mastectomy after a first BC diagnosis. There were no significant differences in the risk of developing contralateral BC or in the immunohistochemical profile between p.R337H and non-p.R337H groups. Conclusions: The expressed phenotype of p.R337H is similar to that of other TP53 pathogenic/likely pathogenic variants, except for an average older age at the onset of disease; however, this is still younger than the general population.

Doenças sexualmente transmissíveis: preservar a confidencialidade do marido ou proteger a saúde da mulher? / Enfermedades de trasmisión sexual: ¿preservar la confidencialidad del marido o proteger la salud de la mujer? / Sexually transmited diseases: to preserve the husband's confidentiality or to protect woman's health?

Manter a privacidade e confidencialidade dos pacientes é crítico na ética. Realizamos estudo exploratório,quanti-qualitativo, com potenciais usuários do Sistema Único de Saúde para identificar como esperam que os profissionais de saúde se comportem quando um dos parceiros de casal heterossexual tem sífilis. Os sujeitos foram funcionários de uma universidade pública. A coleta de dados usou questionário anônimo, auto aplicado, com alternativas de como o profissional deveria agir quando marido com sífilis não quer que sua esposa saiba da doença e pede à equipe que solicitem o exame dela, sem dizer-lhe nada. Como resultado os respondentes esperam a manutenção da confidencialidade, deixando a cargo do marido a revelação da verdade à esposa. O profissional é visto como um mediador da situação, de quem esperam orientação e apoio na revelação. Saber o que esperam os pacientes pode ajudar os enfermeiros a lidar com situações eticamente problemáticas em saúde sexual.

To maintain the privacy and confidentiality of patients is a critical issue for ethics. We developed an exploratory, quantitative and qualitative study with potential users of the Unique Health System to identify how they expect that health personnel would behave when one of the heterosexual partner has syphilis. Subjects were employees of a public University. Data collection was developed through an anonymous and self reported questionnaire, with questions about how the health professional should behave when a husband with syphilis doesn't want his wife to know about the disease and ask the health team to get her examined without knowing about his problem. As results, interviewees expect the maintenance of confidentiality, leaving the husband in charge of telling his wife the truth. Health professionals are seen as a mediator of the situation, of whom they expect orientation and support in the revelation of health problems. To know what the patients expect from health professionals could help nurses to deal with ethical situations that might be a problem among the issues of sexual health.

Mantener la privacidad y confidencialidad de los pacientes es crítico en la ética. Realizamos estudio exploratorio, cuanti-cualitativo con ?potenciales usuarios del Sistema Único de Salud? para identificar como esperan que los profesionales de salud se comporten cuando uno de los compañeros de la pareja heterosexual tiene sífilis. Los sujetos fueron funcionarios de una universidad pública. La colecta de datos usó cuestionario anónimo, autoaplicado, con alternativas de cómo el profesional debería actuar cuando el marido con sífilis no quiere que su esposa sepa de la enfermedad y pide al equipo que soliciten el examen de ella, sin decirle nada. Como resultado los respondientes esperan la manutención de la confidencialidad, dejando a cargo del marido la revelación de la verdad a la esposa. El profesional es visto como un mediador de la situación, de quien esperan orientación y apoyo durante la revelación. Saber lo que esperan los pacientes puede ayudar a los enfermeros a lidiar con situaciones éticamente problemáticas en salud sexual.

Privacidade e confidencialidade em casos de casais discordantes para sífilis / Privacy and confidentiality in syphilis-discordant couples

Estudo exploratório que buscou, junto a usuários da Liga de Combate à Sífilis e outras Doenças Sexualmente Transmissíveis do Hospital das Clínicas da Universidade de São Paulo suas percepções acerca da privacidade e confidencialidade em situação hipotética com casal heterossexual, quando um dos parceiros tem sífilis, e compará-las às percepções encontradas em estudos realizados com profissionais da Estratégia Saúde da Família e "Potenciais usuários do Sistema Único de Saúde". A coleta de dados, realizada através de entrevista semiestruturada, perguntava como o profissional deveria agir numa situação em que um dos parceiros com sífilis não quer revelar o fato à esposa, porém pede que se realize o exame diagnóstico e o tratamento, sem o conhecimento de sua mulher. Foram entrevistados 32 usuários, e a análise dos dados mostrou que existe aceitação da participação do profissional no processo de revelação da verdade, e aproximações entre as percepções dos diversos grupos estudados.