scholarly journals Study of the Carrier State for Five BRCA1/BRCA2 Deleterious Mutations in Bulgarian Women with Breast Cancer

2013 ◽  
Vol 6 (2) ◽  
pp. 100-105 ◽  
Author(s):  
Katia S. Kovacheva ◽  
Zornica B. Kamburova ◽  
Savelina L. Popovska ◽  
Ivan N. Ivanov ◽  
Maria N. Simeonova ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Brca2 Gene ◽  
Carrier State ◽  
University Hospital ◽  
Management Tool ◽  
Deleterious Mutations ◽  
Founder Mutations ◽  
Bulgarian Population ◽  
Brca1 Brca2

SummaryGenetic testing for BRCA 1/2 mutation is a well recognized medical management tool. Identification of healthy carriers of such mutations allows effective risk reduction procedures to be performed. There is no data reported on the founder mutations in the Bulgarian population. To evaluate the contribution of genetic factors to breast cancer (BC), we investigated the carrier state of Bulgarian women with BC for five common (according to BIC database) deleterious BRCA1/2 mutations. The list of patients diagnosed with BC between January 2011 and April 2012 was obtained from the Cancer Registry of University Hospital, Pleven. Eighty-two women with BC were interviewed and a pedigree was constructed of each of them. The patients were classified into seven categories, according to personal, disease and family history. Based on the preliminary prepared selection criteria and the personal family history, we defined a target group of 33 Bulgarian women with BC. They were screened for five deleterious mutations: 5382insC in BRCA1 and 6174delT, 6079del4, 8138del5, 5946delCT in BRCA2, by DNA sequencing. The genetic analysis detected none of the tested mutations. Two polymorphic variants were found in BRCA2 gene: c.5744C>T (rs4987117, SNP database) in exonl 1E in one patient and c.7806-14T>C (rs9534262, SNP database) in exonl7 in 22 patients. In conclusion, without basic information on the founder mutations in the population, the genetic screening for the specific mutations in a small group of tested patients is ineffective.

scholarly journals Characteristics of breast cancer in BRCA1/BRCA2 mutation carriers and non-carriersfrom a genetic counseling unit in Croatia

2020 ◽  
Vol 48 (2-3) ◽  
pp. 54-60
Author(s):  
Snježana Ramić ◽  
◽  
Gabriela Alfier ◽  
Iva Kirac ◽  
Ivan Milas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Brca2 Mutation ◽  
Significant Risk ◽  
Brca2 Gene ◽  
Cancer Risk Assessment ◽  
Luminal B ◽  
Mutation Carriers ◽  
Breast Cancer Risk Assessment ◽  
Brca1 Brca2

Breast cancer (BC) represents 25% of all malignancies in Croatian women, and in 18.8% of cases, it is diagnosed before the age of 50. Croatia launched BRCA testing of people at increased family risk. Hereditary BC is mainly caused by a pathogenic mutation in the BRCA1 or BRCA2 gene and is a significant risk factor for developing breast and ovarian cancer. The present study included 127 women diagnosed with BC, with a strong family history of BC and the known status of the germline mutations in the BRCA1/BRCA2 genes. The majority of women were BRCA1/2 mutation non-carriers, while 15.7% were BRCA1/2 mutation carriers, and 4% had a variant of unknown significance (VUS). BRCA1/2 mutation carriers were younger than non-carriers (median 38.5 years vs. 44 years) (P=.01) and had tumors of higher histological grade (P<.001). The intrinsic subtype of BC differs significantly depending on the type of mutation (P<.001). Triple-negative BC prevailed (87.5%) in BRCA1 mutation carriers, and 12.5% had a luminal B/HER2-negative BC. Four patients were BRCA2 mutation carriers, and two of them had luminal B/HER2-positive BC. Most BRCA1/2 non-carriers (69.2%) and all VUS-carriers have luminal B/HER2-negative BC. Our results show that BRCA1/2 mutation testing is essential for women with a family history burden. It is a piece of valuable information in breast cancer risk assessment and contributes to early diagnosis.

Prevalence of Five BRCA1/2 Mutations in Bulgarian Breast Cancer Patients

2018 ◽  
Vol 11 (2) ◽  
pp. 123-127
Author(s):  
Katia S. Kovacheva ◽  
Zornitsa B. Kamburova ◽  
Savelina L. Popovska ◽  
Dobromir D. Dimitrov ◽  
Ivan N. Ivanov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Age Of Onset ◽  
Point Mutations ◽  
Brca2 Gene ◽  
University Hospital ◽  
Breast Cancer Patients ◽  
Direct Dna Sequencing ◽  
Nccn Guidelines ◽  
Mutational Spectrum ◽  
Bulgarian Population

Summary Detection of mutations in breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) gene is an effective method of early diagnosis and prevention of breast cancer (BC). The mutational spectrum of both genes in Bulgarian population has not been studied in depth. The aim of this study was to investigate the prevalence of five deleterious BRCA1/2 point mutations in high-risk BC women, selected according to the National Comprehensive Cancer Network (NCCN) Guidelines including early age of onset, triple-negative BC and family history of breast or ovarian cancer. The prevalence of two BRCA1 mutations (C61G and 5382insC) and three BRCA2 mutations (6079del4, 9326insA and 9908delA) was evaluated in 80 females with BC, obtained from the Cancer Registry of University Hospital - Pleven. Genetic testing was performed by direct DNA sequencing. One deleterious mutation (5382insC in exon20 in BRCA1) was been found in two patients (2.5%). Both women were diagnosed with BC before age 45. The prevalence of BRCA mutations established in our study was lower than the one found in another preliminary study on Bulgarian population. We concluded that this discrepancy was due to the genetic heterogeneity of the population and the specific mutational spectrum of the BC patients from the Pleven region.

scholarly journals Prevalence of BRCA1 and BRCA2 Mutations Among Patients With Ovarian, Primary Peritoneal, and Fallopian Tube Cancer in India: A Multicenter Cross-Sectional Study

2021 ◽  
pp. 849-861
Author(s):  
Sudeep Gupta ◽  
Senthil Rajappa ◽  
Suresh Advani ◽  
Amit Agarwal ◽  
Shyam Aggarwal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Newly Diagnosed ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
Fallopian Tube Cancer ◽  
Cross Sectional ◽  
Brca2 Mutations ◽  
Brca1 Brca2

PURPOSE There are deficient data on prevalence of germline mutations in breast cancer susceptibility genes 1 and 2 ( BRCA1/ BRCA2) in Indian patients with ovarian cancer who are not selected by clinical features. METHODS This prospective, cross-sectional, noninterventional study in nine Indian centers included patients with newly diagnosed or relapsed epithelial ovarian, primary peritoneal, or fallopian tube cancer. The primary objective was to assess the prevalence of BRCA1/ BRCA2 mutations, and the secondary objective was to correlate BRCA1/ BRCA2 status with clinicopathologic characteristics. Mutation testing was performed by a standard next-generation sequencing assay. RESULTS Between March 2018 and December 2018, 239 patients with a median age of 53.0 (range, 23.0-86.0 years) years were included, of whom 203 (84.9%) had newly diagnosed disease, 36 (15.1%) had family history of ovarian or breast cancer, and 159 (66.5%) had serous subtype of epithelial ovarian cancer. Germline pathogenic or likely pathogenic mutations in BRCA1 and BRCA2 were detected in 37 (15.5%; 95% CI, 11.1 to 20.7) and 14 (5.9%; 95% CI, 3.2 to 9.6) patients, respectively, whereas variants of uncertain significance in these genes were seen in four (1.7%; 95% CI, 0.5 to 4.2) and six (2.5%; 95% CI, 0.9 to 5.4) patients, respectively. The prevalence of pathogenic or likely pathogenic BRCA mutations in patients with serous versus nonserous tumors, with versus without relevant family history, and ≤ 50 years versus > 50 years, were 40 of 159 (25.2%; 95% CI, 18.6 to 32.6) versus 11 of 80 (13.8%; 95% CI, 7.1 to 23.3; P = .0636), 20 of 36 (55.6%; 95% CI, 38.1 to 72.1) versus 41 of 203 (20.2%; 95% CI, 14.9 to 26.4; P < .0001), and 20 of 90 (22.2%; 95% CI, 14.1 to 32.2) versus 31 of 149 (20.8%; 95% CI, 14.6 to 28.2; P = .7956), respectively. CONCLUSION There is a high prevalence of pathogenic or likely pathogenic germline BRCA mutations in Indian patients with ovarian cancer.

scholarly journals Contribution of BRCA1 and BRCA2 germline mutations to early onset breast cancer: a series from north of Morocco

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Joaira Bakkach ◽  
Mohamed Mansouri ◽  
Touria Derkaoui ◽  
Ali Loudiyi ◽  
ElMostafa El Fahime ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Early Onset ◽  
Brca2 Gene ◽  
Germline Mutations ◽  
Genetic Alterations ◽  
Early Onset Breast Cancer ◽  
Brca1 And Brca2 ◽  
Brca Mutations ◽  
History Of

Abstract Background To date, the contribution of BRCA1/2 mutations in Moroccan early onset breast cancer patients remains unknown. Here we assess these genetic alterations for the first time in a cohort from North of Morocco. Methods Thirty-three patients diagnosed with breast cancer at the age of ≤40 years were recruited irrespective of breast and/or ovarian cancer family history. Coding regions and intron-exon boundaries of BRCA1 and BRCA2 genes were sequenced from peripheral blood DNA using Ion Proton (Thermo Fisher Scientific) next generation sequencing platform. Results Overall, five BRCA germline mutations were identified (15.1%). The frequency of mutations among patients with family history of breast cancer was 16.7%. Three mutations were found in BRCA1 (9%) and two within the BRCA2 gene (6%). These are three frameshift mutations (c.798_799del, c.2125_2126insA, c.5116_5119delAATA), one missense (c.116G > A) and one nonsense mutation (c.289G > T). The mutation c.5116_5119delAATA has a founder effect in North Africa. Moreover, one variant of unknown significance was identified in BRCA2 (c.4090A > G). Most BRCA mutations carriers (80%) had no family history of breast cancer. Conclusion Our data do not support the hypothesis that BRCA mutations alone explain the higher frequency of breast cancer in Moroccan young women. The young age (≤40 years) for breast cancer diagnosis seems to be strongly predictive of BRCA mutation status in Moroccan patients. These results will help in decision making with regard to genetic counseling and testing in the national scale.

Changing practice: moving to a specialist nurse-led service for BRCA gene testing

2020 ◽  
Vol 29 (10) ◽  
pp. S6-S13
Author(s):  
Nicola Scott ◽  
Jackie O'Sullivan ◽  
Kristjan Asgeirsson ◽  
Douglas Macmillan ◽  
Emma Wilson
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Cancer Genetics ◽  
Waiting Times ◽  
Brca2 Gene ◽  
Individual Treatment ◽  
Clinical Genetics ◽  
Specialist Nurse ◽  
Gene Testing ◽  
Brca1 Brca2

Some 5–10% of all breast cancers are associated with a pathogenic variant in a breast cancer-associated gene (BRCA1/BRCA2). Historically, with referral to the Nottingham University Hospitals NHS Trust's clinical genetics department for genetic testing, waiting times were on average 12–14 weeks for an initial appointment and 4–6 months to obtain results from the date of testing. A specialist, nurse-led mainstreaming cancer genetics (MCG) service was set up in the trust's Nottingham Breast Institute (NBI) to: reduce waiting times for the initial consultation, counselling, consent and obtaining results for BRCA1/BRCA2 gene testing; and to ensure appropriate patients with breast cancer were offered genetic testing. Two breast clinical nurse specialists were trained so they could counsel, consent and give results for the BRCA1/BRCA2 gene testing directly to patients. Average waiting times for results from the time of testing were reduced to 35.8 days under the nurse-led service, which enabled oncologists and patients to consider individual treatment options at an earlier time. The MCG service reduced waiting times, resulting in an improved, more streamlined service for patients undergoing genetic testing. The MCG service extended the scope of practice of the breast nurse clinical specialists, embedded an expert advanced nursing role in the breast multidisciplinary team and developed nurse mentoring opportunities.

Prevalence and differentiation of hereditary breast and ovarian cancer in Japan.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1534-1534
Author(s):  
Seigo Nakamura ◽  
Takuji Iwase ◽  
Seiichiro Nishimura ◽  
Hideko Yamauchi ◽  
Tadashi Nomizu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Family History ◽  
Brca1 Mutation ◽  
Information Service ◽  
Breast Cancers ◽  
Founder Mutations ◽  
Mutation Site ◽  
Luminal Type ◽  
The U.S

1534 Background: Breast cancer is the most common female cancer, according to the Center for Cancer Control and Information Service in Japan. However, the lifetime breast cancer risk in Japan is markedly lower (one in 16) than in the U.S. or Europe. We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan. Methods: Our study of BRCA 1 and 2 (BRCA1/2) collected data at 8 institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March, 2012. Results: Among 260 proband cases, 46 (17.7%) were positive for BRCA1 and 35 (13.5%) were BRCA2 positive. Therefore, the total pathological mutation rate was 30.7%. Pathology data after breast surgery were obtained from 35 cases of BRCA1 mutation, 22 (62.9%) of which were triple negative and 10 (29.4%) were Luminal type. On the other hand, 24 cases (85.7%) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found 2 cases of large deletion detected by MLPA, comprising the first two reported cases in Japan. One was an entire deletion of exon 20 and the lacked exons 1-9. Eight cases of BRCA1 (3.1%) and 12 (4.6%) BRCA2 were uncertain variants. TN with a family history ovarian cancer were 14/20 (70%), TN under 40 y/o 17/23 (73.9%) and TN with one or more breast cancers in family history 19/32 (59.4%) showed higher incidences of BRCA1/2, especially BRCA1. Conclusions: HBOC may have nearly the same prevalence in Japan as in the U.S. or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to address these challenges: (1) To develop risk models for BRCA1/2 carriers in Japan (2) To identify the proper methods to detect cancer occurrence among Japanese BRCA1/2 carrier early (3) To differentiate whether uncertain mutation variants found in Japan are deleterious.

Outcome of interventions to identify family history and risk management for women with breast cancer in the ambulatory setting

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6121-6121
Author(s):  
N. J. Washburn ◽  
S. Simmons ◽  
V. Sommer ◽  
B. Adkins ◽  
P. Gerken ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Management ◽  
Family History ◽  
Genetic Counselor ◽  
Management Tool ◽  
Ambulatory Setting ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Family History Questionnaire ◽  
Level 1

6121 Background: In 2002, Kansas City Cancer Center (KCCC) performed a quality improvement (QI) project to evaluate how breast cancer patients were being assessed for family history and cancer risk management. A self-administered family history questionnaire was developed to improve the thoroughness of family history collected and education of clinicians was completed to improve the recognition of risk factors based on ASCO guidelines. Methods: Chart audits on 210 women with breast cancer at KCCC, were completed in the second quarter of 2005. All patients were under the age of 65, not undergoing chemotherapy. A risk management tool was developed. Scoring criteria for 2002 was replicated in 2005 as listed in the table . Results: In 2002, 171 pts (89%) had level 1 or 2 family history assessed compared to 207 pts (99%) in 2005, p<0.0001. In 2002, 47% had 3 generations assessed compared to 84% in 2005, p<0.0001. In 2002 and 2005, some risk factor management occurred in both groups, and was equal, 78% and 80% respectively (p=ns). Of those that had risk management 33% had level 1 in 2002 compared to 3% in 2005 (p<0.0001) a 91% reduction in identifying risk without subsequent management. In 2002, 58% had level 2, compared to 71% in 2005 (p=0.02) a 23% improvement in identification & management of risk. In 2002, 9% had level 3 compared to 26% in 2005 (p<0.0001) a 183% improvement in patients with a detailed risk assessment and/or genetic referral. Conclusions: By improving the assessment of family history and education of providers, women with breast cancer are receiving more information to reduce their risk for recurrence and complications. Patients who were identified as high risk for BRCA1 or BRCA2 mutations were referred to either a nurse practitioner or genetic counselor. [Table: see text] No significant financial relationships to disclose.

scholarly journals BRCA mutation carrier detection. A model-based cost-effectiveness analysis comparing the traditional family history approach and the testing of all patients with breast cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (3) ◽  
pp. e000328 ◽  
Author(s):  
Jan Norum ◽  
Eli Marie Grindedal ◽  
Cecilie Heramb ◽  
Inga Karsrud ◽  
Sarah Louise Ariansen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Family History ◽  
Brca Mutation ◽  
Unit Cost ◽  
Cost Effectiveness Analysis ◽  
University Hospital ◽  
Healthcare Perspective ◽  
Model Based ◽  
Effectiveness Analysis

BackgroundIdentification of BRCA mutation carriers among patients with breast cancer (BC) involves costs and gains. Testing has been performed according to international guidelines, focusing on family history (FH) of breast and/or ovarian cancer. An alternative is testing all patients with BC employing sequencing of the BRCA genes and Multiplex Ligation Probe Amplification (MLPA).Patients and methodsA model-based cost-effectiveness analysis, employing data from Oslo University Hospital, Ullevål (OUH-U) and a decision tree, was done. The societal and the healthcare perspectives were focused and a lifetime perspective employed. The comparators were the traditional FH approach used as standard of care at OUH-U in 2013 and the intervention (testing all patients with BC) performed in 2014 and 2015 at the same hospital. During the latter period, 535 patients with BC were offered BRCA testing with sequencing and MLPA. National 2014 data on mortality rates and costs were implemented, a 3% discount rate used and the costing year was 2015. The incremental cost-effectiveness ratio was calculated in euros (€) per life-year gained (LYG).ResultsThe net healthcare cost (healthcare perspective) was €40 503/LYG. Including all resource use (societal perspective), the cost was €5669/LYG. The univariate sensitivity analysis documented the unit cost of the BRCA test and the number of LYGs the prominent parameters affecting the result.Diagnostic BRCA testing of all patients with BC was superior to the FH approach and cost-effective within the frequently used thresholds (healthcare perspective) in Norway (€60 000–€80 000/LYG).

scholarly journals Breast Cancer Family History and Contralateral Breast Cancer Risk in Young Women: An Update From the Women’s Environmental Cancer and Radiation Epidemiology Study

2018 ◽  
Vol 36 (15) ◽  
pp. 1513-1520 ◽  
Author(s):  
Anne S. Reiner ◽  
Julia Sisti ◽  
Esther M. John ◽  
Charles F. Lynch ◽  
Jennifer D. Brooks ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Population Based ◽  
Deleterious Mutations ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Chek2 1100Delc ◽  
Cancer Family History ◽  
Radiation Epidemiology ◽  
Breast Cancer Family History

Purpose The Women’s Environmental Cancer and Radiation Epidemiology (WECARE) study demonstrated the importance of breast cancer family history on contralateral breast cancer (CBC) risk, even for noncarriers of deleterious BRCA1/2 mutations. With the completion of WECARE II, updated risk estimates are reported. Additional analyses that exclude women negative for deleterious mutations in ATM, CHEK2*1100delC, and PALB2 were performed. Patients and Methods The WECARE Study is a population-based case-control study that compared 1,521 CBC cases with 2,212 individually matched unilateral breast cancer (UBC) controls. Participants were younger than age 55 years when diagnosed with a first invasive breast cancer between 1985 and 2008. Women were interviewed about breast cancer risk factors, including family history. A subset of women was screened for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2. Rate ratios (RRs) were estimated using multivariable conditional logistic regression. Cumulative absolute risks (ARs) were estimated by combining RRs from the WECARE Study and population-based SEER*Stat cancer incidence data. Results Women with any first-degree relative with breast cancer had a 10-year AR of 8.1% for CBC (95% CI, 6.7% to 9.8%). Risks also were increased if the relative was diagnosed at an age younger than 40 years (10-year AR, 13.5%; 95% CI, 8.8% to 20.8%) or with CBC (10-year AR, 14.1%; 95% CI, 9.5% to 20.7%). These risks are comparable with those seen in BRCA1/2 deleterious mutation carriers (10-year AR, 18.4%; 95% CI, 16.0% to 21.3%). In the subset of women who tested negative for deleterious mutations in BRCA1/2, ATM, CHEK2*1100delC, and PALB2, estimates were unchanged. Adjustment for known breast cancer single-nucleotide polymorphisms did not affect estimates. Conclusion Breast cancer family history confers a high CBC risk, even after excluding women with deleterious mutations. Clinicians are urged to use detailed family histories to guide treatment and future screening decisions for young women with breast cancer.

Sign in / Sign up

Export Citation Format

Share Document