Characterization of HSD17B1 sequence variants in breast cancer cases from French Canadian families with high risk of breast and ovarian cancer

BackgroundWomen with germ line BRCA1 or BRCA2 mutations have a marked increased risk of breast and ovarian cancer compared with the general population, whereas risk-reducing salpingo-oophorectomy (RRSO) significantly lowers the incidence of these cancers. The objective of this study was to review the clinical and pathological characteristics of a French Canadian population undergoing RRSO. Surgical morbidity was also evaluated.Materials and MethodsFrom December 1999 to December 2009, all women who underwent RRSO at our institution were identified. Medical records were retrospectively reviewed. Descriptive statistics, the Fischer exact test, and the Student t test were used for analysis.ResultsDuring the study period, RRSO was performed on 119 women. Mean age at surgery was 49 years (35–72 years), and 63 patients (53%) were premenopausal. Sixty-two women (52%) had a history of in situ or invasive breast cancer. BRCA1 and BRCA2 mutations were present in 34 patients (29%) and 42 patients (35%), respectively, whereas 43 patients (36%) were considered to have an increased risk of breast and ovarian cancer, despite a personal genetic test, which was either negative (n = 23) or unknown because the patient declined genetic testing (n = 20). Most patients with a uterus in place had a complementary hysterectomy (65%). Six complications occurred (3 hematomas, 2 cardiac arrhythmias, and 1 cystotomy). In one patient (0.8%), a high-grade stage II ovarian cancer was discovered at the time of surgery. Fallopian tube atypias were identified on final pathology in 8 cases (6.7%). After a median follow-up of 22 months, 4 women (3.4%) developed breast cancer and one woman (0.8%) developed peritoneal cancer.ConclusionsRisk-reducing salpingo-oophorectomy is highly effective in preventing ovarian, fallopian tube, and breast cancers in a high-risk French Canadian population; and the surgical morbidity is low.

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Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer

Journal of Medical Genetics ◽

10.1136/jmg.2006.044388 ◽

2006 ◽

Vol 44 (2) ◽

pp. 107-121 ◽

Cited By ~ 48

Author(s):

J. Simard ◽

M. Dumont ◽

A.-M. Moisan ◽

V. Gaborieau ◽

H. Vezina ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Risk Prediction ◽

Prediction Models ◽

Brca2 Mutation ◽

French Canadian ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Risk Prediction Models ◽

Testing Approach

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Clinical Considerations ofBRCA1- andBRCA2-Mutation Carriers: A Review

International Journal of Surgical Oncology ◽

10.1155/2011/374012 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 9

Author(s):

O. Bougie ◽

J. I. Weberpals

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

High Risk ◽

Significant Risk ◽

Surgical Prophylaxis ◽

Breast And Ovarian Cancer ◽

Screening Guidelines ◽

Mutation Carriers ◽

Clinical Considerations

Individuals who carry an inherited mutation in the breast cancer 1 (BRCA1) andBRCA2genes have a significant risk of developing breast and ovarian cancer over the course of their lifetime. As a result, there are important considerations for the clinician in the counseling, followup and management of mutation carriers. This review outlines salient aspects in the approach to patients at high risk of developing breast and ovarian cancer, including criteria for genetic testing, screening guidelines, surgical prophylaxis, and chemoprevention.

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Molecular and genealogical characterization of the R1443X BRCA1 mutation in high-risk French-Canadian breast/ovarian cancer families

Human Genetics ◽

10.1007/s00439-005-1297-9 ◽

2005 ◽

Vol 117 (2-3) ◽

pp. 119-132 ◽

Cited By ~ 37

Author(s):

Hélène Vézina ◽

Francine Durocher ◽

Martine Dumont ◽

Louis Houde ◽

Csilla Szabo ◽

...

Keyword(s):

Ovarian Cancer ◽

High Risk ◽

Brca1 Mutation ◽

French Canadian

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2067 Developing a cultural adaptation of a telephone genetic counseling intervention for Latina women at-risk of hereditary breast and ovarian cancer

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.249 ◽

2018 ◽

Vol 2 (S1) ◽

pp. 68-68

Author(s):

Alejandra Hurtado de Mendoza ◽

Sara Gómez Trillos ◽

Marc Schwartz ◽

Beth Peshkin ◽

Heidi E. Hamilton ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

High Risk ◽

Cancer Survivors ◽

Cultural Adaptation ◽

Limited English Proficiency ◽

Breast Cancer Survivors ◽

Evidence Based ◽

Breast And Ovarian Cancer

OBJECTIVES/SPECIFIC AIMS: The overall goal of this project is to enhance the use of GCRA in Latina breast cancer survivors at high risk of hereditary breast and ovarian cancer to reduce disparities in GCRA uptake. The aims of the study are to (1) develop a cultural adaptation of an evidence-based TGC intervention that consists of phone genetic counseling and a booklet, (2) evaluate the impact of TGC Versus Usual Care, and (3) explore the communication patterns in TGC and genetic counseling sessions with an interpreter. METHODS/STUDY POPULATION: We are conducting a 2-phase, mixed methods study. In Phase I we will develop a cultural adaption of an evidence-based intervention (TGC) for high-risk Latina breast cancer survivors using the Learner Verification and Revision Framework (n=15). In Phase II we will use a cluster randomized design with four community sites randomized to Spanish TGC (n=2 sites) or usual care (n=2 sites) (n=60; 15 per site). The primary outcome is genetic counseling uptake. Among women who receive genetic counseling either through TGC (n~30) or with an interpreter (n~15), we will assess counseling quality by reviewing 20 randomly selected audiotaped sessions (10 TGC; 10 interpreters). We will evaluate women’s HBOC knowledge and satisfaction with counseling. Communication processes and outcomes will be assessed using gold standard RIAS quantitative coding system and qualitative discourse analysis. RESULTS/ANTICIPATED RESULTS: We elicited input from transdisciplinary team members to develop an initial adaptation of a TGC print booklet and intervention protocol for use with high-risk Latina breast cancer survivors with limited English proficiency. The booklet contains low-literacy information about HBOC, risk factors, pros and cons of testing, and management strategies. Based on these materials and prior work, we anticipate TGC will consist of one 1 hour or less TGC session by phone. Participants interested in pursuing testing will receive a saliva kit and will participate in a second TGC session (30 min) to discuss test results and management options. DISCUSSION/SIGNIFICANCE OF IMPACT: Given access barriers and the shortage of Spanish-speaking genetic counselors, adapting and translating TGC intervention is a promising strategy that could reduce disparities by broadening the reach and accessibility to genetic counseling while enhancing the quality of the service for Latinas with limited English proficiency.

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The Importance of Extended Analysis Using Current Molecular Genetic Methods Based on the Example of a Cohort of 228 Patients with Hereditary Breast and Ovarian Cancer Syndrome

Genes ◽

10.3390/genes12101483 ◽

2021 ◽

Vol 12 (10) ◽

pp. 1483

Author(s):

Luise D. Resch ◽

Alrun Hotz ◽

Andreas D. Zimmer ◽

Katalin Komlosi ◽

Nina Singh ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

High Risk ◽

Molecular Genetic ◽

Pathogenic Variant ◽

Molecular Diagnostic ◽

Cancer Syndrome ◽

Breast And Ovarian Cancer ◽

Extended Analysis ◽

Pathogenic Gene

In about 20–30% of all women with breast cancer, an increased number of cases of breast cancer can be observed in their family history. However, currently, only 5–10% of all breast cancer cases can be attributed to a pathogenic gene alteration. Molecular genetic diagnostics underwent enormous development within the last 10 years. Next-generation sequencing approaches allow increasingly extensive analyses resulting in the identification of additional candidate genes. In the present work, the germline molecular diagnostic analysis of a cohort of 228 patients with suspected hereditary breast and ovarian cancer syndrome (HBOC) was evaluated. The 27 pathogenic gene variants initially detected are listed, and their distribution in the high-risk BRCA1 and BRCA2 genes is presented in this study. In ten high-risk patients, in whom, to date, no pathogenic variant could be detected, an extended genetic analysis of previously not considered risk genes was performed. Three variants of uncertain significance and one pathogenic variant could be described. This proves the importance of extended analysis using current molecular genetic methods.

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Screening of CHEK2 and TP53 p.R337H germ-line mutations in high-risk patients for hereditary breast and ovarian cancer from northeast of Brazil.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.1539 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 1539-1539

Author(s):

Ivana Lucia Oliveira Nascimento ◽

Gabriela Espirito Santo Felix ◽

Taisa Manuela Bonfim Machado-Lopes ◽

Thais Bomfim ◽

Maura Romeo ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

High Risk ◽

Cellular Response ◽

Germ Line ◽

Susceptibility Genes ◽

Breast And Ovarian Cancer ◽

High Risk Patients ◽

High Penetrance ◽

Risk Patients

1539 Background: CHEK2 is a molecular messenger that interacts with a checkpoint network of other susceptibility genes like ATM, BRCA1, TP53, MDM2, Cdc25A and Cdc25C. The mission of these checkpoints is to preserve the genome integrity during the cell division by regulating the cellular response to DNA damages. The TP53 p.R337H germline mutation was studied in patients with Li-Fraumeni Syndrome, breast cancer and Choroid plexus carcinomas in Southern of Brazil, but never in the Northeast. In the hereditary breast cancer the mutation frequencies of susceptibility genes of low penetrance like CHEK2 is 1-10%, while for genes of high penetrance as TP53 is <1%. Thus, the aim of this study was to screening for CHEK2 and TP53 most common germline mutations in high-risk patients for hereditary breast and ovarian cancer (HBOC) from Northeast of Brazil. Methods: It was analyzed 100 high-risk patients for HBOC from Bahia, Brazil. The genomic DNA was extract from peripheral blood. The CHEK2 mutations, c.1100delC, c.444+1G>A and p.I157T, and TP53 p.R337H mutation were genotyped by Allelic Specific-PCR or PCR-RFLP. Results: Most of the subjects had only breast cancer (86.0%), followed by ovarian (7.0%) and both breast and ovarian cancer (7.0%). Among the breast cancer cases the most common histological type was the ductal (71.0%), while among the ovarian cancer cases were the serous (57.14%). The mean age at diagnostic was 42 yrs (± 9.99). Any of the patient presented c.1100delC, c.444+1G>A and p.I157T mutations. But, two have the p.R337H mutation. Conclusions: Though there is the hypothesis that mutations of low penetrance genes, such as CHEK2, are more likely to be found than high penetrance genes, such as TP53, here it was demonstrate that three of most predisposing variants of CHEK2, c.1100delC, c.444+1G>A and p.I157T, do not have major contribution in HBOC in the population studied. While, the p.R337H, though presented in low frequency compared with the Southern of Brazil (Ashton-Prolla et al., 2012), seems to have a significant contribution in HBOC.

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Genetic Testing to Guide Risk-Stratified Screens for Breast Cancer

Journal of Personalized Medicine ◽

10.3390/jpm9010015 ◽

2019 ◽

Vol 9 (1) ◽

pp. 15 ◽

Cited By ~ 11

Author(s):

Ava Willoughby ◽

Paul Andreassen ◽

Amanda Toland

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Testing ◽

High Risk ◽

Cancer Susceptibility ◽

Cancer Surveillance ◽

Risk Scores ◽

Breast And Ovarian Cancer ◽

Cancer Susceptibility Genes ◽

Uncertain Significance

Breast cancer screening modalities and guidelines continue to evolve and are increasingly based on risk factors, including genetic risk and a personal or family history of cancer. Here, we review genetic testing of high-penetrance hereditary breast and ovarian cancer genes, including BRCA1 and BRCA2, for the purpose of identifying high-risk individuals who would benefit from earlier screening and more sensitive methods such as magnetic resonance imaging. We also consider risk-based screening in the general population, including whether every woman should be genetically tested for high-risk genes and the potential use of polygenic risk scores. In addition to enabling early detection, the results of genetic screens of breast cancer susceptibility genes can be utilized to guide decision-making about when to elect prophylactic surgeries that reduce cancer risk and the choice of therapeutic options. Variants of uncertain significance, especially missense variants, are being identified during panel testing for hereditary breast and ovarian cancer. A finding of a variant of uncertain significance does not provide a basis for increased cancer surveillance or prophylactic procedures. Given that variant classification is often challenging, we also consider the role of multifactorial statistical analyses by large consortia and functional tests for this purpose.

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