Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation-Negative Hereditary Breast Cancer Families

e22191 Background: Hereditary breast cancer accounts for 3–8% of all breast cancers. It was recently estimated that a combination of BRCA1 and BRCA2 genes mutations is responsible for 30% of hereditary breast cancer cases. Methods: To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, 36 patients who had at least one first degree relative affected with breast and/or ovarian cancer were analysed. Thirty three patients are suggestive of BRCA1 mutation and 3 are suggestive of BRCA2 mutation. Results: Four mutations in BRCA1 gene were described among which, one novel splice site mutation (330 dupA) and 3 frameshift mutations including the 4160 delAG, the 2789 delG and the 5385 insC. Our study is the first to describe the 5385 insC mutation which was described only among Jewish Ashkenazi population. Two frameshift mutations (1537 del4 and 5909 insA) were screened in BRCA2 gene. Nineteen percent (7/36) of the familial cases were altered on BRCA1 or BRCA2 genes with deleterious mutations at heterozygous state and 55% (20/36) by mutation with uncertain value (UV) or by single nucleotide polymorphisms (SNPs). Conclusions: Almost all the cases mutated by deleterious mutations on BRCA1 gene reported a family history of breast and/or ovarian cancer in the index case or in their relatives. On the contrary, patients with an UV mutation or SNPs have no history of ovarian cancer in their corresponding families. Our data are the first to contribute to information on mutation spectrum of BRCA genes and offer a recommended screening mode for clinical genetic testing policy in Tunisia. No significant financial relationships to disclose.

Download Full-text

Outcome of ovarian cancer after breast cancer in BRCA1 and BRCA2 mutation carriers

British Journal of Cancer ◽

10.1038/bjc.2016.333 ◽

2016 ◽

Vol 115 (10) ◽

pp. 1174-1178 ◽

Cited By ~ 2

Author(s):

Leendert H Zaaijer ◽

Helena C van Doorn ◽

Marian J E Mourits ◽

Marc van Beurden ◽

Joanne A de Hullu ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Mutation Carriers

Download Full-text

P4-11-04: Risk of Primary (PBC) and Contralateral Breast Cancer (CBC) after Ovarian Cancer (OC) in BRCA1 and BRCA2 Mutation Carriers; Implications for Surveillance and Risk Reducing Mastectomy.

10.1158/0008-5472.sabcs11-p4-11-04 ◽

2011 ◽

Author(s):

C Seynaeve ◽

P Vencken ◽

M Hooning ◽

M Menke-Pluymers ◽

A Heemskerk-Gerritsen ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Contralateral Breast Cancer ◽

Brca2 Mutation ◽

Contralateral Breast ◽

Brca1 And Brca2 ◽

Mutation Carriers ◽

Risk Reducing

Download Full-text

BRCA1 and BRCA2 Mutation Frequency in Women Evaluated in a Breast Cancer Risk Evaluation Clinic

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.4.994 ◽

2002 ◽

Vol 20 (4) ◽

pp. 994-999 ◽

Cited By ~ 28

Author(s):

Helen A. Shih ◽

Fergus J. Couch ◽

Katherine L. Nathanson ◽

M. Anne Blackwood ◽

Timothy R. Rebbeck ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Evaluation ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Brca1 Mutations ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

PURPOSE: To determine the prevalence of BRCA1 and BRCA2 mutations in families identified in a breast cancer risk evaluation clinic. PATIENTS AND METHODS: One hundred sixty-four families seeking breast cancer risk evaluation were screened for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS: Mutations were identified in 37 families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2 mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1) were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one family (0.6%) despite estimates of equal frequency in the Ashkenazi population. In contrast to other series, the average age of breast cancer diagnosis was earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1 mutations (37.6 years, P = .028). BRCA1 mutations were detected in 20 (45.5%) of 44 families with ovarian cancer and 12 (75%) of 16 families with both breast and ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two [4.5%] of 44) were detected in families with ovarian cancer (P = .01). Eight families had male breast cancer; one had a BRCA1 mutation and three had BRCA2 mutations. CONCLUSION: BRCA1 mutations were three times more prevalent than BRCA2 mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast and ovarian cancer in a single individual, and male breast cancer were all significantly more common in families with BRCA1 and BRCA2 mutations, but none of these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was noted.

Download Full-text

Common Variants at the 19p13.1 and ZNF365 Loci Are Associated with ER Subtypes of Breast Cancer and Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Cancer Epidemiology Biomarkers & Prevention ◽

10.1158/1055-9965.epi-11-0888 ◽

2012 ◽

Vol 21 (4) ◽

pp. 645-657 ◽

Cited By ~ 38

Author(s):

Fergus J. Couch ◽

Mia M. Gaudet ◽

Antonis C. Antoniou ◽

Susan J. Ramus ◽

Karoline B. Kuchenbaecker ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Cancer Risk ◽

Brca2 Mutation ◽

Ovarian Cancer Risk ◽

Common Variants ◽

Brca1 And Brca2 ◽

Mutation Carriers

Download Full-text

A comparison of BRCA1 and BRCA2 risk assessment models

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10034 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10034-10034

Author(s):

S. Panchal ◽

M. Ennis ◽

H. Yee ◽

V. Contiga ◽

L. J. Bordeleau

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Risk Assessment ◽

Pearson Correlation ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Degree Relative ◽

Tertiary Referral Center ◽

Risk Assessment Models ◽

Large Breast

10034 Background: A number of models of varying complexity are available to calculate the risk of carrying a BRCA1 or BRCA2 mutation causing hereditary breast and ovarian cancer. A >10% risk of carrying a BRCA1 or BRCA2 mutation is commonly used to establish testing eligibility in North America (testing threshold). We have compared these risk assessment models to ascertain their utility in patients from a large breast cancer program in our tertiary referral center. Methods: Risk assessment calculations were performed using the BRCAPRO, Myriad, Manchester, and UPennII models for all new probands referred to our clinic at Mount Sinai Hospital, Toronto (Canada), between May and October 2005. Individuals with a known familial mutation were excluded. Pearson correlation coefficients and pairwise scatterplots were performed for each pair of models. Regression analyses were developed to explore how well the BRCAPRO model can be predicted by other models. Results: 103 probands were included in our analyses (97% female, mean age: 50 yrs, 22% of Ashkenazi Jewish descent, 52.4% affected with breast cancer, 67% with ≥ one 1st degree relative affected with breast or ovarian cancer). The proportion of probands meeting the testing threshold based on each model was: BRCAPRO (34.0%), Myriad (33.0%), Manchester (55.3%), and UPennII (46.6%). Correlations calculated for each pair of models were large (range: 0.48–0.86). In comparing two of the most clinically relevant models (BRCAPRO and UPennII), the proportion of probands meeting the testing threshold was significantly higher using the UPennII model (p=0.0036). Between these two models, a higher correlation was observed for BRCA1 than for BRCA2 (R=0.76, R=0.58, respectively). The UPennII model was the strongest univariate predictor of the BRCAPRO results. Conclusions: All risk assessment models predicted a substantial proportion of patients referred to our clinic to be eligible for testing (≥ 33% of probands). A significantly higher proportion of probands were eligible for testing when using the UPennII model compared to the BRCAPRO model. This difference is in part due to the differential inclusion of prostate/pancreatic cancers and of third degree relatives with cancer in these models. An exploration of the sensitivity and specificity of these models will be presented. No significant financial relationships to disclose.

Download Full-text

Hereditary Breast-Ovarian Cancer at the Bedside: Role of the Medical Oncologist

Journal of Clinical Oncology ◽

10.1200/jco.2003.05.096 ◽

2003 ◽

Vol 21 (4) ◽

pp. 740-753 ◽

Cited By ~ 39

Author(s):

Henry T. Lynch ◽

Carrie L. Snyder ◽

Jane F. Lynch ◽

Bronson D. Riley ◽

Wendy S. Rubinstein

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Genetic Counseling ◽

Family History ◽

High Risk ◽

Hereditary Breast Cancer ◽

Present Report ◽

Brca1 And Brca2 ◽

Cancer Family ◽

Hereditary Breast Ovarian Cancer

Purpose: To provide practical considerations for diagnosing, counseling, and managing patients at high risk for hereditary breast cancer. Design: We have studied 98 extended hereditary breast cancer (HBC)/hereditary breast-ovarian cancer (HBOC) families with BRCA1/2 germline mutations. From these families, 1,315 individuals were counseled and sampled for DNA testing. Herein, 716 of these individuals received their DNA test results in concert with genetic counseling. Several challenging pedigrees were selected from Creighton University’s hereditary cancer family registry, as well as one family from Evanston/Northwestern Healthcare, to be discussed in this present report. Results: Many obstacles were identified in diagnosis, counseling, and managing patients at high risk for HBC/HBOC. These obstacles were early noncancer death of key relatives, perception of insurance or employment discrimination, fear, anxiety, apprehension, reduced gene penetrance, and poor compliance. Other important issues such as physician culpability and malpractice implications for failure to collect or act on the cancer family history were identified. Conclusion: When clinical gene testing emerged for BRCA1 and BRCA2, little was known about the efficacy of medical interventions. Potential barriers to uptake of testing were largely unexplored. Identification and referral of high-risk patients and families to genetic counseling can greatly enhance the care of the population at the highest risk for cancer. However, because premonitory physical stigmata are absent in most of these syndromes, an HBOC diagnosis may be missed unless a careful family history of cancer of the breast, ovary, or several integrally associated cancers is obtained.

Download Full-text

Genotype/Phenotype Correlations in Patients with Hereditary Breast Cancer

Breast Care ◽

10.1159/000380900 ◽

2015 ◽

Vol 10 (1) ◽

pp. 22-26 ◽

Cited By ~ 6

Author(s):

Maike Wittersheim ◽

Reinhard Büttner ◽

Birgid Markiefka

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Hereditary Breast Cancer ◽

Sporadic Breast Cancer ◽

Germline Mutations ◽

Breast Cancers ◽

High Susceptibility ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Distinct Morphology

Of all breast cancer cases, 5-10% can be attributed to germline mutations, and the high-susceptibility genes BRCA1 and BRCA2 account for about 25-28% of these cases. For the remainder, several genes of moderate and low penetrance have been discovered. Histopathologic characteristics have been studied in small cohorts, but for most of the known non-BRCA1/2-associated hereditary breast cancers, the histologic and immunohistochemical phenotypes are not yet identified. Particularly BRCA1 tumors are associated with a distinct morphology and immunohistochemical characteristics that differ from sporadic breast cancer of age-matched controls. The recognition of features characteristic of these mutations can be helpful to identify patients likely to carry a germline mutation and to assess which gene should be screened for first, in families with a high occurrence of breast and ovarian cancer.

Download Full-text