5101 POSTER 86 Cases of Early-onset Breast Cancer in Hungary – Retrospective Analysis of Immunohistochemistry (IHC) and Family-history Data -Assessing the Risk of Carrying BRCA1 and BRCA2 Mutation

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.

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Family History of Breast and Ovarian Cancers and BRCA1 and BRCA2 Mutations in a Population-Based Series of Early-Onset Breast Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/93.16.1215 ◽

2001 ◽

Vol 93 (16) ◽

pp. 1215-1223 ◽

Cited By ~ 156

Author(s):

N. Loman ◽

O. Johannsson ◽

U. Kristoffersson ◽

H. Olsson ◽

A. Borg

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Population Based ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Ovarian Cancers ◽

History Of ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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BRCA1 and BRCA2 Germline Mutations in Malaysian Women with Early-Onset Breast Cancer without a Family History

PLoS ONE ◽

10.1371/journal.pone.0002024 ◽

2008 ◽

Vol 3 (4) ◽

pp. e2024 ◽

Cited By ~ 34

Author(s):

Gaik Theng Toh ◽

Peter Kang ◽

Sharlene S. W. Lee ◽

Daphne Shin-Chi Lee ◽

Sheau Yee Lee ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Early Onset ◽

Germline Mutations ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Malaysian Women

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Abstract 5598: Germline TP53 mutation in very early onset breast cancer patients without BRCA1 and BRCA2 mutation in Brazilian population

10.1158/1538-7445.am2011-5598 ◽

2011 ◽

Author(s):

Marina C. Cannavan ◽

Bianca CG Lisboa ◽

Maria M. Brentani ◽

Edenir I. Palmero ◽

Ghyslaine Martel-Planche ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Onset ◽

Tp53 Mutation ◽

Brca2 Mutation ◽

Brazilian Population ◽

Breast Cancer Patients ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Germline Tp53 Mutation

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Hereditary Susceptibility to Breast Cancer: Significance of Age of Onset in Family History and Contribution of BRCA1 and BRCA2

Disease Markers ◽

10.1155/1999/291023 ◽

1999 ◽

Vol 15 (1-3) ◽

pp. 89-92 ◽

Cited By ~ 14

Author(s):

Thomas S. Frank ◽

Amie M. Deffenbaugh ◽

Mark Hulick ◽

Kathryn Gumpper

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Early Onset ◽

Age Of Onset ◽

Early Onset Breast Cancer ◽

Brca1 And Brca2 ◽

Degree Relative ◽

Age Of Diagnosis ◽

History Of

OBJECTIVE: To correlate mutations in BRCA1 and BRCA2 with family history of breast cancer in a first-degree relative for women diagnosed with breast cancer before age 45 who do not have a personal or family history of ovarian cancer.METHODS: Family history for women with breast cancer diagnosed before age 45 was provided by ordering physicians via a test requisition form designed for this purpose. Gene analysis was performed by dye primer sequencing for the entire coding regions of BRCA1 and BRCA2. Because a personal and family history of ovarian cancer are known to be significantly associated with mutations, women with either were excluded from analysis.RESULTS: Overall, deleterious mutations in BRCA1 or BRCA2 were identified in 85 of 440 women (19%) with breast cancer under 45. Mutations were identified in 73 of 276 women (26%) with a first degree family history of breast cancer compared to 12 of 164 without (7%) (P <.0001). When results were analyzed by the age of diagnosis in first degree relatives, mutations were identified in 56 of 185 women (30%) with at least one first degree relative with breast cancer diagnosed before age 50 compared with 17 of 91 women (19%), where the first degree family history of breast cancer was at or over age 50 (P = .042).CONCLUSION: Among women with breast cancer diagnosed before age 45, a first-degree relative diagnosed with the disease under age 50 is an indicator of a mutation in BRCAl or BRCA2 even in the absence of a family history of ovarian cancer. Therefore, women diagnosed with early-onset breast cancer should be asked about the age of onset in any first-degree relative diagnosed with the disease, as well as about any family history of ovarian cancer. Mutations in BRCA2 account for a substantial proportion of hereditary breast cancer. Therefore, studies that are limited to BRCA1 or that do not analyze by age of onset of breast cancer in relatives may underestimate the contribution of mutations in BRCAl and BRCA2 to women with early onset breast cancer.

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