Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil.

BACKGROUND: BRCA1/2 pathogenic (P) and likely pathogenic (LP) germline variants are frequent among patients with ovarian carcinoma. However, these variants have not been extensively characterized in patients with ovarian cancer in Brazil. METHODS: In this retrospective study we evaluated clinical characteristics and BRCA1/2 genetic test results from patients with ovarian carcinoma who underwent genetic counseling at A.C.Camargo Cancer Center (Brazil) between 2015 and 2017 and had performed germline genetic testing of BRCA1/2 genes. RESULTS: Among 158 patients, 33 P and LP variants and were found (20.8%), 27 in BRCA1 and six in BRCA2, and six variants of unknown clinical significance (VUS). Thirteen percent of the patients did not have Multiplex Ligation-dependent Probe Amplification (MLPA) results. Three P variants in BRCA1 were found in more than one patient: c.5266dupC (p.Gln1756Profs*74), c.3331_3334delCAAG (p.Gln1111Asnfs5*), and c.211A > G (p.Arg71Gly). One LP variant in BRCA1 had not been previously described, c.4153_4154delCT (p.Leu1385Ilefs*5). Patients with previous diagnosis of breast cancer were carriers of P or LP variant in 8 of 12 cases (66.7%), and patients with a family history of ovarian or breast cancer in first- or second-degree relatives were carriers of P or LP variant in 26.7% of cases compared to 16.9% for patients without family history (p = 0.166). CONCLUSION: Prevalence of BRCA1/2 germline P and LP variants is slightly higher than previously described by the largest occidental studies, with a high prevalence of variant c.5266dupC (p.Gln1756Profs*74) in BRCA1 observed. Moreover, we identified a new LP variant.

Prognostic impact of platinum sensitivity in ovarian carcinoma patients with brain metastasis.

BACKGROUND: Brain metastasis (BM) is a rare event in ovarian cancer patients. The current prognostic scores that have been used for other tumors do not account for specific characteristics of ovarian cancer, such as platinum sensitivity. METHODS: This retrospective cohort study examined patients with ovarian carcinoma and BM who were treated at a single institution from January 2007 to December 2017. Clinical data on the diagnosis of BM and follow-up were collected. Cox regression was used to evaluate prognostic factors for overall survival (OS). RESULTS: Of 560 patients, 26 presented with BM. Eight patients were treated with surgery, 15 with whole-brain radiotherapy (RT), and 5 with stereotactic RT, and 4 patients received systemic treatment at the diagnosis of BM. The median OS was 10.8 months. The following factors were associated with OS: platinum-sensitive recurrence (HR 0.34, 95% CI 0.12-0.99; p = 0.049), higher number of previous treatment lines (HR 1.57, 95% CI 1.12-2.19; p = 0.008), ECOG performance status (HR 2.52, 95% CI 1.24-5.09; p = 0.010), and longer interval from initial diagnosis to BM (p = 0.025). Notably, the number of brain metastasis, the largest tumor size, and progression outside of the CNS were not related to survival. Platinum sensitivity was not associated with any of the classic prognostic factors in brain metastasis patients such as number or size of brain metastasis or disease progression outside the CNS strengthening the hypothesis of the importance of platinum sensitivity to the prognosis of ovarian cancer patients with BM. CONCLUSIONS: The factors related to the biological behavior of the ovarian cancer such as platinum sensitivity at the time of BM diagnosis, fewer number of previous treatment lines and interval from initial diagnosis were associated with survival in ovarian cancer patients with BM, while factors that are usually related to survival in BM in other cancers were not associated with survival in this cohort of ovarian cancer patients. The small number of patients did not allow us to exclude the prognostic role of these former factors that were not associated with survival in the present cohort.

Combined endocrine and targeted therapy in luminal breast cancer.

Introduction: For decades, endocrine therapy has been the cornerstone of management for luminal breast cancer. Despite the substantial benefit derived by patients from endocrine therapy, primary and secondary resistances to endocrine therapy are serious clinical issues.Areas covered: Today, in the advanced setting, three distinct classes of targeted agents mTOR, CDK 4/6, and PI3K inhibitors, are approved for use. CDK 4/6 inhibitors have improved outcomes substantially, changing the natural history of advanced luminal breast cancer. Current studies seek to bring CDK 4/6 inhibitors to the early setting. This review will cover all available data on target therapy combinations with endocrine therapy for both the early and advanced settings, including approved drugs and agents in development.Expert opinion: Combined endocrine and target therapy has changed the landscape in advanced disease. In early disease, it is possible to have a large impact, particularly in patients with higher risk of relapse. Trials like ADAPTCYCLE seek to leverage neoadjuvant data to de-escalate treatment, substituting chemotherapy for CDK 4/6 inhibitors. In advanced diseases, studies such as PADA-1 point toward a future in which ctDNA will be used to define management before clinical progression occurs.

Prevalência de genótipos em portadores crônicos do vírus da hepatite C / Prevalence of genotypes in patients with chronic hepatitis C virus

Objetivo: Conhecer a prevalência dos genótipos do vírus da hepatite C, comparando-a com os dados de trabalhos semelhantes realizados no país. Métodos: Estudo observacional descritivo retrospectivo, no qual foi analisado o banco de dados do Laboratório Central de Saúde Pública do Espírito Santo, para verificação de exames realizados no período de dezembro de 2004 a dezembro de 2012. Resultados: Foram analisados 1.649 registros de pacientes anti-HCV positivos submetidos à detecção da quantificação do RNA do vírus da hepatite C e genotipagem. O RNA viral foi detectado em 72,71% dos pacientes analisados. O genótipo mais prevalente foi o 1, com 79,10%, seguido do 3, com 16,70%, do 2, com 3,24% e do 4, com 0,96%. Não tiveram sua genotipagem descrita 151 portadores do vírus. Os subgenótipos mais frequente dentre os examinados foram os tipos 1a e 1b, apresentando, inclusive, um genótipo duplo 2a/2c. Conclusão: Os dados refletiram a situação epidemiológica em relação aos portadores crônicos e prevalência de genótipos.

Objective: To know the prevalence of genotypes of hepatitis C virus, comparing it with data from similar studies conducted in Brazil. Methods: Retrospective descriptive observational study in which we analyzed the database of the Central Public Health Laboratory of the state of Espirito Santo, to check the exams performed from December 2004 to December 2012. Results: The records of 1649 patients who were anti-HCV-positive and underwent HCV RNA detection and genotypingwere analyzed. The viral RNA was detected in 72.71 % of these patients. The most prevalent genotype was genotype 1 with 79.10 %, followed by 16.70% with genotype 3, 3.24 % with genotype 2, and 0.96 % with genotype 4. The genotyping of 151 carriers of the virus was not described. The most common subgenotypes were types 1a and 1b, even with a double 2a/2c genotype. Conclusions: Data reflect the epidemiological situation regarding chronic carriers and prevalence of genotypes.