Histological and Immunohistochemical Characteristics for Hereditary Breast Cancer Risk in a Cohort of Brazilian Women / Características histológicas e imunohistoquímicas para risco hereditário de câncer de mama em uma coorte de mulheres brasileiras

Abstract Objective The study aimed to characterize the clinical, histological, and immunohistochemical profile of women with invasive breast cancer, according to the risk for Hereditary Predisposition Breast and Ovarian Cancer Syndrome in a Brazilian population. Methods This is a retrospective study performed from a hospital-based cohort of 522 women, diagnosed with breast cancer treated at an oncology referral center in the Southeast region of Brazil, between 2014 and 2016. Results Among the 430 women diagnosed with invasive breast cancer who composed the study population, 127 (29.5%) were classified as at increased risk for hereditary predisposition to breast and ovarian cancer syndrome. There was a lower level of education in patients at increased risk (34.6%) when compared with those at usual risk (46.0%). Regarding tumor characteristics, women at increased risk had higher percentages of the disease diagnosed at an advanced stage (32.3%), and with tumors > 2cm (63.0%), with increased prevalence for both characteristics, when compared with those at usual risk. Furthermore, we found higher percentages of HG3 (43.3%) and Ki-67 ≥ 25% (64.6%) in women at increased risk, with prevalence being about twice as high in this group. The presence of triple-negative tumors was observed as 25.2% in women at increased risk and 6.0% in women at usual risk, with the prevalence of absence of biomarkers being 2.5 times higher among women in the increased risk group. Conclusion From the clinical criteria routinely used in the diagnosis of breast cancer, the care practice of genetic counseling for patients at increased risk of hereditary breast cancer in contexts such as Brazil is still scarce.

Resumo Objetivo O presente estudo buscou caracterizar o perfil clínico, histológico e imunohistoquímico de mulheres com câncer de mama invasivo segundo o risco para a Síndrome de Predisposição Hereditária ao Câncer de Mama e Ovário em uma população brasileira. Métodos Trata-se de um estudo retrospectivo realizado a partir de uma coorte hospitalar composta por 522 mulheres diagnosticadas com câncer de mama entre 2014 e 2016 assistidas em um centro de referência oncológica localizado na região sudeste brasileira. Resultados Entre as 430 mulheres diagnosticadas com câncer de mama invasivo que compuseram a população de estudo, 127 (29,5%) foram classificadas como de risco aumentado para a síndrome de predisposição hereditária ao câncer de mama e ovário. Verificou-se menor nível de escolaridade nas pacientes com risco aumentado (34,6%) quando comparadas àquelas consideradas como de risco habitual (46,0%). Quanto às características do tumor, as mulheres de risco aumentado apresentaram maiores percentuais de doença diagnosticada em estádio avançado (32,3%) e com tumores > 2cm (63,0%), com prevalência aumentada para ambas as características, quando comparadas àquelas de risco habitual. Ainda nas mulheres de risco aumentado, foram encontrados maiores percentuais de GH3 (43,3%) e Ki-67 ≥ 25% (64,6%), com prevalência cerca de duas vezes maior neste grupo. A presença de tumores triplo-negativos foi observada em 25,2% nas mulheres de risco aumentado e 6,0% nas mulheres de risco habitual, com prevalência de ausência de biomarcadores 2,5 vezes maior entre as mulheres do grupo de risco aumentado. Conclusão A partir dos critérios clínicos rotineiramente utilizados no diagnóstico do câncer de mama, a prática assistencial do aconselhamento genético para as pacientes com risco aumentado de câncer de mama hereditário em contextos como o do Brasil ainda é escarça.

Germline genetic mutations in high-risk patients for breast cancer: profile of a group in the city of Florianopolis, Santa Catarina

To analyze the occurrence of genetic mutations in a sample of patients with high risk of breast cancer in Florianopolis/ SC from December 1st, 2021, to January 31, 2022. Methods: An observational, descriptive and retrospective study carried out through data collection of a preexisting database. A total of 194 tests were analyzed. Of these, 192 met the inclusion criteria and composed the final sample of 205 genes. Data were classified and reported the frequency and percentage of the variables: gene and presence or absence of mutation. Results: Mean age of the analyzed patients was 52.3 years, and most underwent the test due to personal history of breast cancer (80%). Clinical significance classification showed that, of the 192 gene panels, 62% were variants of uncertain significance; 14% were pathogenic; and 24%, negative. Of the 205 mutations, the most prevalent genes were: ATM 8.7%, MUTYH 5.8%, POLE 5.8%, BRCA2 4.8%, MSH6 4.8% and RECQL4 4.8%. Of the pathogenic tests regarding genetic predisposition to cancer (n=38/14.1%), the most common mutations were MUTYH (23%) and BRCA1 (15%), with mean age of 52 years (±14.3). In variants of uncertain significance panels (n=168/62%) the frequency rates were ATM (7.7%), POLE (7.1%) and MSH6 (5.9%) genes. The high penetrance genes were present in 18% of the genetic predisposition to cancer panels. Of those with positive family history (n=40), 19% of the genes were pathogenic, 53% were variants of uncertain significance; and 26% were negative. Furthermore, in patients with pathogenic mutations and positive family history (n=11), the most common mutations were in BRCA1 (27%) and BRCA2 (27%). Of the patients who tested due to personal history (n=152), 64% of the genes presented variants of uncertain significance, 13% were pathogenic and 22% were negative.

Hereditary breast cancer ­ what we have learned in the last decade

This literature review aims to inform and assist physicians and other health professionals in managing all information related to hereditary breast cancer, which is in constant and rapid growth, allowing for improvement in patient care and assistance. In addition, we seek to better identify which patients are eligible for the clinical criteria of association with risk of hereditary breast cancer, based on international recommendations and highlighting the main high and moderate penetrance genes that make up the multigenic panels for germline investigation in breast cancer, as well as the possibilities of clinical management that must be considered when complex decisions are required in clinical practice. Nowadays, there is more interest in population screening, in a greater supply of genetic tests, more genes included in multigene panels ­ allowing the search for genetic counseling ­, apart from the need for clinical-decision support.

Comparison of hereditary breast and ovarian cancer syndrome and sporadic ovarian cancer in ovarian cancer BRCA mutations / 中华妇产科杂志

Objective:To study the difference between BRCA gene mutations in hereditary breast and ovarian cancer syndrome (HBOC) and in sporadic ovarian cancer (SOC).Methods:This study was for exploratory research, the inclusion criteria were 284 patients with ovarian cancer admitted at Shanxi Provincial Cancer Hospital from November 2018 to December 2019, with high-throughput DNA sequencing including the full coding regions and exon-intron link regions of BRCA1 and BRCA2 gene. Pathogenic mutations in the BRCA gene of patients with ovarian cancer were collected and mutation site analysis was performed to compare phenotypic differences in pathogenic mutations between HBOC syndrome and SOC patients.Results:(1) Of the 284 ovarian cancer patients, seventy-seven had BRCA pathogenic mutations with a mutation rate of 27.1% (77/284), with BRCA1 mutation rate of 19.7% (56/284), BRCA2 gene 6.7% (19/284) and BRCA1/2 common mutation rate of 0.7% (2/284). Of the 284 patients with ovarian cancer, the pathogenic mutation rate in the BRCA gene in HBOC syndrome patients was 43.8% (32/73), which were significantly higher than that in SOC patients [21.3% (45/211); χ2=13.905, P<0.01]. Among BRCA1 gene mutation, the mutation rate in HBOC syndrome was higher than that of SOC [87.5% (28/32) vs 62.2% (28/45)], the BRCA2 gene mutation rate in patients with HBOC syndrome was lower than that in SOC patients [6.2% (2/32) vs 37.8% (17/45)], and there were statistically significant differences (all P<0.05). Two of the 77 patients with pathogenic mutations in the BRCA gene were multisite mutations, including one simultaneous two site mutation, one simultaneous three site mutation. There were 80 mutation sites with frameshift deletion mutations (55.0%, 44/80) and nonsense mutations (31.2%, 25/80). (2) Of the 73 patients with HBOC syndrome, 32 cases had pathogenic mutations in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (9 and 7 cases, respectively), and only two cases in BRCA2, both in exon 11; another two had multiple locus mutations. Of the 211 patients with SOC, 45 cases had pathogenic mutants in BRCA gene, including 28 cases in BRCA1, mainly in exon 11 and 24 (15 and 2 cases, respectively), and 17 cases in BRCA2, mainly in exon 11 (11 cases). (3) Thirty-four pathogenic mutation sites in BRCA gene were found newly, twenty of them were located in the BRCA1 gene, including a locus located on the intron 6, 301+1G>A, and the remaining 19 sites were located on the exons, including 283_286delCTTG, 68_69delAG, 132C>T, 514_547+3del37, 742delA, 1126_1129delAATA, 1196delA, 1352_1364del, 1465G>T, 2171delC, 2341G>T, 3359_3363delTTAAT, 4085_4086ins11, 4161_4162delTC, 4165_4166delAG, 4258G>T, 4338_4339del8insAGAA, 4468G>T, and 4783delA; fourteen sites were located in the BRCA2 gene, including a locus located on the intron 7, 631+1G>A, and the remaining 13 sites were located on the exons, including 2648delT, 2914A>T, 2950_2951insG, 4357+1G>A, 5054C>T, 5257A>T, 5291_5292insTC, 5913delT, 3593delA, 6091_6092insA, 6135_6136delTT, 7452delT, 9097_9098insA. A tal of 28 repeat mutations were located in the BRCA1 gene; among them, the site 5470_5477del8 was repeated 6 times, while 3 times in 981_982delAT. Conclusions:Patients with HBOC syndrome have a significantly higher rate of pathogenic mutation in the BRCA gene than that in patients with SOC. BRCA gene pathogenic mutation sites in HBOC syndrome patients occur commonly in exon 11 and 24 of BRCA 1 gene, while SOC patients occur mainly in exon 11 and 24 of BRCA1 gene and exon 11 of BRCA2 gene. The two loci of BRCA1∶5470_5477del8, BRCA1∶981_982delAT may be ancestor mutations in Chinese ovarian cancer patients, and 34 newly discovered pathogenic mutations in the BRCA gene, enriching the BRCA gene mutation spectrum in the Chinese population.

Clinical Validity of Next-Generation Sequencing Multi-Gene Panel Testing for Detecting Pathogenic Variants in Patients With Hereditary Breast-Ovarian Cancer Syndrome

BACKGROUND: Hereditary breast and ovarian cancer syndrome (HBOC) is caused by pathogenic variants in BRCA and other cancer-related genes. We analyzed variants in BRCA gene and other cancer-related genes in HBOC patients to evaluate the clinical validity of next-generation sequencing (NGS) multi-gene panel testing. METHODS: The BRCA1/2 NGS testing was conducted for 262 HBOC patients. Multiplex ligation-dependent probe amplification and direct Sanger sequencing were performed for confirmation. Multi-gene panel testing was conducted for 120 patients who did not possess BRCA1/2 pathogenic variants but met the National Comprehensive Cancer Network criteria. RESULTS: Pathogenic variants in BRCA1/2 were detected in 30 HBOC patients (11.5%). Additionally, four out of the 120 patients possessed pathogenic variants by multi-gene panel testing (3.3%): MSH2 (c.256G>T, p.Glu86*), PMS2 (c.1687C>T, p.Arg563*), CHEK2 (c.546C>A, p.Tyr182*), and PALB2 (c.3351-1G>C). All the four patients had a family history of cancer. CONCLUSIONS: Multi-gene panel testing could be a significant screening tool for HBOC patients, especially for those with a family history of cancer.

BRCA1 and BRCA2 mutations in a sample of breast and ovarian cancer families from the Colombian pacific / Mutaciones en los genes BRCA1 y BRCA2 en una muestra de familias con cáncer de mama y/u ovario del pacífico colombiano

Abstract Introduction: Breast cancer is the most common neoplasia of women from all over the world especially women from Colombia. 5%­10% of all cases are caused by hereditary factors, 25% of those cases have mutations in the BRCA1/BRCA2 genes. Objective: The purpose of this study was to identify the mutations associated with the risk of familial breast and/or ovarian cancer in a population of Colombian pacific. Methods: 58 high-risk breast and/or ovarian cancer families and 20 controls were screened for germline mutations in BRCA1 and BRCA2, by Single Strand Conformation Polymorphism (SSCP) and sequencing. Results: Four families (6.9%) were found to carry BRCA1 mutations and eight families (13.8%) had mutations in BRCA2. In BRCA1, we found three Variants of Uncertain Significance (VUS), of which we concluded, using in silico tools, that c.81­12C>G and c.3119G>A (p.Ser1040Asn) are probably deleterious, and c.3083G>A (p.Arg1028His) is probably neutral. In BRCA2, we found three variants of uncertain significance: two were previously described and one novel mutation. Using in silico analysis, we concluded that c.865A>G (p.Asn289Asp) and c.6427T>C (p.Ser2143Pro) are probably deleterious and c.125A>G (p.Tyr42Cys) is probably neutral. Only one of them has previously been reported in Colombia. We also identified 13 polymorphisms (4 in BRCA1 and 9 in BRCA2), two of them are associated with a moderate increase in breast cancer risk (BRCA2 c.1114A>C and c.8755­66T>C). Conclusion: According to our results, the Colombian pacific population presents diverse mutational spectrum for BRCA genes that differs from the findings in other regions in the country.

Resumen Introducción: El cáncer de mama es la neoplasia más común en mujeres de todo el mundo, y, también de Colombia. 5% a 10% de todos los casos son causados por factores hereditarios; 25% de estos casos tienen mutaciones en los genes BRCA1/BRCA2. Objetivo: El propósito de este estudio fue el de identificar mutaciones asociadas con riesgo de cáncer de mama y/u ovario familiar en pacientes del pacífico colombiano. Métodos: Fueron revisados para mutaciones en BRCA1 y BRCA2 de línea germinal mediante SSCP y secuenciación 58 familias de alto riesgo para cáncer de mama y/u ovario y 20 controles Resultados: cuatro familias (6.9%) presentaron mutaciones en BRCA1 y ocho familias (13.8%) en BRCA2. En BRCA1, encontramos tres variantes de significado clínico desconocido (VUS), de las cuales concluimos, usando herramientas bioinformáticas, que c.81­12C>G y c.3119G>A (p.Ser1040Asn) son probablemente deletéreas, y c.3083G>A (p.Arg1028His) es probablemente neutral. En BRCA2, encontramos tres VUS: una mutación nueva y dos previamente descritas, usando análisis bioinformáticos, concluimos que c.865A>G (p.Asn289Asp) y c.6427T>C (p.Ser2143Pro) son probablemente deletéreas y c.125A>G (p.Tyr42Cys) es probablemente neutral. Solo una de ellas ha sido reportada previamente en Colombia. También identificamos 13 polimorfismos (4 en BRCA1 y 9 en BRCA2), dos de ellos asociados con un moderado incremento del riesgo para cáncer de mama (BRCA2 c.1114A>C and c.8755­66T>C). Conclusión: de acuerdo con nuestros resultados, la población del suroccidente colombiano presenta un espectro mutacional diverso para los genes BRCA que difiere de lo encontrado en otras regiones del país.

The influence of BRCA variants of unknown significance on cancer risk management decision-making / 부인종양

OBJECTIVE: To compare gynecological cancer risk management between women with BRCA variants of unknown significance (VUS) to women with negative genetic testing METHODS: Ninety-nine patients whose BRCA genetic testing yielded VUS were matched with 99 control patients with definitive negative BRCA results at a single institution. Demographics and risk management decisions were obtained through chart review. Primary outcome was the rate of risk-reducing bilateral salpingo-oophorectomy (RRBSO). Chi square tests, t-tests, and logistic regression were performed, with significance of p<0.05. RESULTS: VUS patients were more likely to be non-Caucasian (p=0.000) and of Ashkenazi-Jewish descent (p=0.000). There was no difference in gynecologic oncology referrals or recommendations to screen or undergo risk-reducing surgery for VUS vs. negative patients. Ultimately, 44 patients (22%) underwent RRBSO, with no significant difference in surgical rate based on the presence of VUS. Ashkenazi-Jewish descent was associated with a 4.5 times increased risk of RRBSO (OR=4.489; 95% CI=1.484–13.579) and family history of ovarian cancer was associated with a 2.6 times risk of RRBSO (OR=2.641; 95% CI=1.107–6.299). CONCLUSION: In our institution, patients with VUS were surgically managed similarly to those with negative BRCA testing. The numbers of patients with VUS are likely to increase with the implementation of multi-gene panel testing. Our findings underscore the importance of genetic counseling and individualized screening and prevention strategies in the management of genetic testing results.

Contralateral Breast Cancer and Ipsilateral Breast Tumor Recurrence in BRCA1/2 Carriers and Non-Carriers at High-Risk of Hereditary Breast Cancer / 한국유방암학회지

Knowledge and Anxiety Related to Hereditary Ovarian Cancer in Serous Ovarian Cancer Patients / 여성건강간호학회지

PURPOSE: The awareness of hereditary breast and ovarian cancer (HBOC) and BRCA testing is increasing in Korea. Compared to the sizable research on HBOC knowledge among breast cancer women, studies in the ovarian cancer population are limited. This paper aimed to investigate the level of knowledge of hereditary ovarian cancer and anxiety in women diagnosed with serous ovarian cancer in Korea and determine differences in the knowledge and anxiety according to whether genetic testing was undertaken and whether BRCA1 or BRCA2 mutations were present.METHODS: Using a descriptive research design, a cross-sectional survey was conducted on 100 women diagnosed with serous ovarian cancer at N hospital in Gyeonggi-do, Korea, from July to November 2018. The collected data were analyzed by descriptive statistics, independent t-tests, one-way analysis of variance, and Pearson's correlation coefficient using the SPSS 21.0 program.RESULTS: The hereditary ovarian cancer-related knowledge score was mid-level (mean score 8.90±3.29 out of a total of 17), as was the state anxiety level was mid-level (mean score 47.96±3.26 out of possible score range of 20–80). Genetic knowledge of hereditary ovarian cancer was associated with age, education, occupation, genetic counseling, and BRCA mutations. There were no statistically significant factors related to anxiety and there were no statistically significant correlations between knowledge level and anxiety.CONCLUSION: More comprehensive education on gene-related cancer is needed for ovarian cancer patients, especially for items with low knowledge scores. A genetic counseling protocol should be developed to allow more patients to alleviate their anxiety through genetic counseling.

A Study on Genetic Knowledge and Anxiety in Patients with Breast Cancer

PURPOSE: The purpose of the study was to understand the levels of knowledge about hereditary breast cancer and anxiety among patients with breast cancer and to identify the relationship between knowledge and anxiety. METHODS: The data were collected from 100 patients with breast cancer in Seoul in 2013. A 15-item hereditary breast cancer knowledge questionnaire and 20-item anxiety state questionnaire were used to measure knowledge and anxiety, respectively. The data were analyzed using descriptive statistics, t-tests, one-way ANOVA, LSD post hoc tests, and Cronbach's α tests in SPSS/WIN 21.0. RESULTS: The mean score of knowledge was 8.34±3.17, indicating 0.56 when converted to 1. Knowledge was different by age, education, marital status, monthly family income, risk for hereditary breast cancer, and needs for genetic counseling. The mean score of anxiety was 46.05±10.53. There was positive correlation between knowledge and anxiety (r=.25, p=.014). CONCLUSION: The results of this study indicate that oncology professionals need to provide genetic knowledge for early detection and prevention of secondary cancer to patients with breast cancer, while considering and relieving their emotional distress, such as anxiety.

Síndrome de cáncer hereditario de mama y ovario: aplicación clínica / Hereditary breast and ovarian cancer syndrome: Clinical application

Aportar al ginecólogo herramientas para la identificación de pacientes con riesgo de síndrome de cáncer hereditario de mama y ovario (SCHMO), y brindar consejería en el manejo preventivo de pacientes con este síndrome.Materiales y métodos: a partir de un caso hipotético se formulan preguntas relacionadas con el riesgo de desarrollar cáncer de mama y ovario en pacientes con SCHMO. Para responder estas preguntas se realizó una revisión de la literatura pertinente en las bases de datos Medline vía PubMed, ScienceDirect y SciELO. Se utilizaron los términos MESH "Síndrome de cáncer de mama y ovario hereditario", "Neoplasias ováricas", "Neoplasias de la mama", "Genes BRCA1", "Genes BRCA2" y su equivalente en inglés. Los resultados se restringieron a artículos publicados entre el 2005 y 2015.Resultados: a través de la búsqueda en PubMed se obtuvieron 56 artículos, de los cuales se seleccionaron 45. En ScienceDirect y SciELO se encontraron 7 artículos. Además, se incluyeron 4 artículos de fuentes no ligadas a estas bases de datos.Conclusiones: el ginecoobstetra debe identificar pacientes con riesgo de presentar el síndrome de cáncer hereditario de mama y ovario, y explicar a los pacientes la importancia de la realización de las pruebas moleculares de los genes BRCA1 y BRCA2 y de participar en equipos multidisciplinarios que además deben incluir al genetista, cirujano, los oncólogos y al paciente para la toma de decisiones médicas de acuerdo con los resultados moleculares...

To provide gynaecologists with tools for the identification of patients at risk of hereditary breast and ovarian cancer syndrome (HBOC) and present advise regarding the preventive management of patients with this syndrome.Materials and methods: Questions were asked in relation to the risk of patients with HBOC developing breast and ovarian cancer. To answer those questions, a review of the relevant literature was conducted in the Medline database via PubMed, and in ScienceDirect and SciELO. The MESH terms used were Breast and Ovarian Cancer Syndrome, Ovarian Neoplasms, Breast Neoplasms, BRCA1 Genes, BRCA2 Genes, and their equivalent in English. Results were limited to articles published between 2005 and 2015.Results: Overall, 56 articles were found in PubMed, of which 45 were selected. The search in ScienceDirect and SciELO resulted in 7 articles. Additionally, 4 articles from other sources not linked to these data bases were also included.Conclusions: Obstetric gynaecologists must identify patients at risk of presenting Hereditary Breast and Ovarian Cancer Syndrome, and explain to the patients the importance of performing molecular testing for BRCA1 and BRCA2 genes; and they must participate in multi-disciplinary teams consisting also of geneticists, surgeons, oncologists and patients for medical decision-making in accordance with the molecular results...

Analysis of BRIP1 Variants among Korean Patients with BRCA1/2 Mutation-Negative High-Risk Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The aim of the current study is to assess the spectrum of genetic variation in the BRIP1 gene among Korean high-risk breast cancer patients who tested negative for the BRCA1/2 mutation. MATERIALS AND METHODS: Overall, 235 Korean patientswith BRCA1/2 mutation-negative high-risk breast cancerwere screened for BRIP1 mutations. The entire BRIP1 gene was analyzed using fluorescent-conformation sensitive gel electrophoresis. In silico analysis of BRIP1 variants was performed using PolyPhen-2 and SIFT. RESULTS: A total of 20 sequence alterations including 12 exonic and eight intronic variantswere found. Among the 12 exonic variants, 10 were missense and two were silent mutations. No protein-truncating mutation was found among the tested patients. Among the 10 missense variants, four (p.L263F, p.L340F, p.L474P, and p.R848H) were predicted to be pathogenic by both PolyPhen-2 and SIFT, and these variants were found in five patients. Of the four missense variants, p.L263F, p.L474P, and p.R848H localize to regions between the helicase motifs, while p.L340F resides in an iron-sulfur domain of BRIP1. CONCLUSION: No protein-truncating mutation in BRIP1 was found among the tested patients. The contribution of BRIP1 variants is thought to be minor in Korean non-BRCA1/2 high-risk breast cancer.

Association of family risk and lifestyle/comorbidities in ovarian cancer patients / Associação de história familiar e estilo de vida a comorbidades em pacientes com câncer de ovário.

Summary Objectives: to analyze factors that might indicate familial predisposition for ovarian cancer in patients diagnosed with this disease. Methods: in a prospective single center cohort study at the Institute of Cancer of the State of São Paulo (ICESP), 51 women diagnosed with ovarian cancer were included. Familial predisposition for ovarian cancer was defined as having a higher than 10% chance of having a BRCA1/2 mutation according to the Manchester scoring system, a validated method to assess the likelihood of mutation detection. Each patient was interviewed with a standardized questionnaire on established risk factors for ovarian cancer and other factors that might influence the risk to develop ovarian cancer. Logistic regression analyses were performed to estimate the impact of the evaluated factors on the likelihood of mutation detection, by calculating odds ratios and 95% confidence intervals. Results: seventeen out of 51 patients had a family history of breast and/or ovarian cancer, four patients had a history of breast or endometrial cancer, 11 were diagnosed before the age of 50, and 12 presented a risk of familial predisposition to ovarian cancer higher than 10%. Patients with comorbidities, such as hypertension, diabetes, hormonal disorders, dyslipidemia and psychiatric conditions, presented a lower chance of having a familial predisposition for ovarian cancer (OR: 0.22; 95% CI: 0.06-0.88; p=0.03). Conclusion: in this study, having comorbidities was associated with a lower risk of having a familial predisposition for ovarian cancer. Other factors associated with the risk of ovarian cancer did not have an impact on this predisposition. .

Resumo Objetivos: analisar fatores que possam indicar uma predisposição familiar ao câncer de ovário em pacientes com este diagnóstico. Métodos: em estudo de coorte prospectiva realizado no Instituto do Câncer do Estado de São Paulo (ICESP), foram incluídas 51 mulheres diagnosticadas com câncer de ovário entre janeiro de 2009 e dezembro de 2011. Predisposição familiar para câncer de ovário foi definida como um risco maior de 10% de apresentar uma mutação em BRCA1/2, de acordo com o sistema de pontes de Manchester, um método validado para avaliar a probabilidade de detecção de mutação nesses genes. Cada paciente foi entrevistada com um questionário padronizado, abordando fatores de risco para câncer de ovário e outros fatores que pudessem influenciar o risco de desenvolver a doença. O impacto dos fatores avaliados na probabilidade de detecção da mutação foi avaliado com regressões logísticas. Resultados: dezessete das 51 pacientes referiram história familiar de câncer de mama e/ou ovário, quatro pacientes apresentavam antecedente pessoal de câncer de mama ou endométrio, 11 haviam sido diagnosticadas antes dos 50 anos e 12 apresentaram um risco maior que 10% de predisposição familiar a câncer de ovário. Pacientes com comorbidades como hipertensão, diabetes, disfunções hormonais, dislipidemia e distúrbios psiquiátricos apresentaram menor risco de predisposição familiar ao câncer de ovário (OR: 0.22; IC 95%: 0.06-0.88; p=0.03). Conclusão: neste estudo, apresentar alguma comorbidade foi associado a um menor risco de ter uma predisposição familiar ao câncer de ovário. Outros fatores associados ao risco de câncer de ovário não tiveram nenhum impacto sobre esta predisposição. .