scholarly journals Breast cancer in young women: prevalence of LOH at p53, BRCA1 and BRCA2

10.1186/bcr96 ◽  
2000 ◽  
Vol 2 (S1) ◽  
Author(s):  
SM Johnson ◽  
JA Shaw ◽  
RA Walker
Keyword(s):  
Breast Cancer ◽  
Young Women ◽  
Brca1 And Brca2

scholarly journals Risk of Asynchronous Contralateral Breast Cancer in Noncarriers of BRCA1 and BRCA2 Mutations With a Family History of Breast Cancer: A Report From the Women's Environmental Cancer and Radiation Epidemiology Study

2013 ◽  
Vol 31 (4) ◽  
pp. 433-439 ◽  
Author(s):  
Anne S. Reiner ◽  
Esther M. John ◽  
Jennifer D. Brooks ◽  
Charles F. Lynch ◽  
Leslie Bernstein ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Young Women ◽  
Contralateral Breast Cancer ◽  
Contralateral Breast ◽  
Brca1 And Brca2 ◽  
Bilateral Disease ◽  
History Of ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Purpose To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations. Patients and Methods From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history–specific 10-year cumulative absolute risks of CBC were estimated. Results Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%. Conclusion Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.

scholarly journals Contribution of BRCA1 and BRCA2 Germline Mutations to Early Algerian Breast Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Sarra Henouda ◽  
Assia Bensalem ◽  
Rym Reggad ◽  
Nedda Serrar ◽  
Leila Rouabah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Young Women ◽  
Significant Proportion ◽  
Case Series ◽  
Germline Mutations ◽  
Genomic Rearrangement ◽  
Brca1 And Brca2 ◽  
Exon 2 ◽  
Large Genomic Rearrangement ◽  
Algerian Population

Breast cancer is the most common female malignancy and the leading cancer mortality cause among Algerian women. Germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast cancer have not been clearly identified within the Algerian population. It is necessary to study the BRCA1/2 genes involvement in the Algerian breast cancer occurrence. We performed this study to define germline mutations in BRCA1/2 and their implication in breast cancer among young women from eastern Algeria diagnosed or treated with primary invasive breast cancer at the age of 40 or less who were referred to Anti-Cancer Center of Setif, Algeria. Case series were unselected for family history. Eight distinct pathogenic mutations were identified in eight unrelated families. Three deleterious mutations and one large genomic rearrangement involving deletion of exon 2 were found in BRCA1 gene. In addition, four mutations within the BRCA2 gene and one large genomic rearrangement were identified. Novel mutation was found among Algerian population. Moreover, five variants of uncertain clinical significance and favor polymorphisms were identified. Our data suggest that BRCA1/2 mutations are responsible for a significant proportion of breast cancer in Algerian young women.

Clinicopathological features and BRCA1 and BRCA2 mutation status in a prospective cohort of young women with breast cancer

2021 ◽  
Author(s):  
Yaileen D. Guzmán-Arocho ◽  
Shoshana M. Rosenberg ◽  
Judy E. Garber ◽  
Hilde Vardeh ◽  
Philip D. Poorvu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Young Women ◽  
Prospective Cohort ◽  
Brca2 Mutation ◽  
Clinicopathological Features ◽  
Brca1 And Brca2 ◽  
Mutation Status

BRCA1 and BRCA2 Nucleotide Variants in Young Women with Therapy Related Acute Myeloid Leukemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1102-1102 ◽  
Author(s):  
Michael G. Martin ◽  
Meagan Jacoby ◽  
Jin Shao ◽  
Elena Deych ◽  
Timothy Graubert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Dna Repair ◽  
Acute Myeloid Leukemia ◽  
Young Women ◽  
Myeloid Leukemia ◽  
Brca1 And Brca2 ◽  
Goodness Of Fit Test ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Abstract 1102 Poster Board I-124 Background Therapy-related acute myeloid leukemia (t-AML) is a lethal iatrogenic complication of radiation therapy and chemotherapy. It is unclear whether t-AML represents a truly stochastic event, or if individuals have different degrees of susceptibility. It has been shown that women diagnosed with breast cancer younger than 50 are at the highest risk of developing subsequent AML compared to age-matched controls (RR 4.14). This may either reflect more aggressive therapy given to younger women or differences in their ability to tolerate chemotherapy, perhaps through germline polymorphisms in DNA repair or drug metabolism genes. BRCA1 and BRCA2 genes are involved in DNA repair and germline variants confer an increased risk of breast cancer at a young age (median age at diagnosis 40 and 41, respectively) as well as an increased risk of ovarian cancer. The age-dependent risk of t-AML in breast cancer survivors mirrored the risk of a subsequent diagnosis of ovarian cancer, suggesting a common genetic factor may be responsible. Therefore, we hypothesized that young women with breast cancer that develop t-AML would have an increased prevalence of BRCA1 or BRCA2 mutations compared to the predicted prevalence of mutations based on age, personal and family history. Methods We identified 13 women under the age of 50 that were treated at our institution for t-AML following a diagnosis of breast cancer (median age = 43.5). Each chart was reviewed for family and personal history of breast cancer and ovarian cancer. The predicted prevalence of mutations in BRCA1 and BRCA2 were calculated from tables developed by Myriad Genetic Laboratories and the number of expected cases was calculated with a weighted sum. Normal DNA obtained from a skin biopsy was sequenced for BRCA1 and BRCA2 in 11 women and bone marrow DNA was sequenced in 1 woman in whom a skin sample was unavailable. One woman had a known deleterious mutation in BRCA2 and only the exon containing the mutation was resequenced. Total exonic sequencing, including splice sites, was performed (excluding BRCA2 exon 12, and partial coverage of BRCA2 exon 20 that failed primer design). There are no described deleterious mutations in exon 12 in the On-line Breast Cancer Mutation Data Base (BIC) (http://research.nhgri.nih.gov/ projects/bic/). Statistical differences between the observed versus expected frequencies of nucleotide variants were compared using the Chi-square goodness-of-fit test. Functional significance of nucleotide variants were determined using BIC, SIFT (http://blocks.fhcrc.org/sift/SIFT.html), FastSNP (http://fastsnp.ibms.sinica.edu.tw/pages/-input_CandidateGeneSearch.jsp) and PolyPhen (http://genetics.bwh.harvard.edu/pph/) computational algorithms. Results The expected number of patients harboring mutant BRCA1 or BRCA2 alleles was 1.46 in these 13 patients (11%). We identified 4 patients with sequence variants predicted to alter function in the 13 patients (31%), which represents a statistically significant increase over the expected frequency (p=0.026). Of the 4 mutations, two (BRCA2 - S1760X and BRCA2 – F1182X) are known to be deleterious in BIC, and one (BRCA1 - Q356R, found in 2 patients) is of uncertain significance in BIC, and is computationally predicted to disrupt protein function by SIFT, FastSNP, and PolyPhen algorithms. The functional consequence of each nucleotide change is being tested using DNA repair activity assays in isogenic cell lines expressing either the wild-type or mutant allele. Discussion In this study, we observed an increased prevalence of mutations in BRCA1 and BRCA2 in young women with breast cancer treated with chemotherapy and/or radiotherapy that developed t-AML, suggesting that alterations in DNA repair genes may be important for the development of t-AML. A case-control study is being performed to validate this finding in a larger group of uniformly treated breast cancer patients. Disclosures No relevant conflicts of interest to declare.

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