294P - High frequency of BRCA 1/2 mutations among Israeli non Ashkenazi breast cancer patients

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Breast Cancer, Early Stage
Familial Cancer
Presenter Firas Elyan
Authors F. Elyan1, O. Maimon2, A.F. Salah3, M. Sagi4, L. Kaduri2, I. Lerer4, Y. Goldberg4, T. Hamburger2, D. Bercovich5, T. Peretz-Yablonski6
  • 2Sharett Institute Of Oncology, HADASSAH-HEBREW UNIVERSITY MEDICAL CENTER, jerusalem/IL
  • 3Oncology And Radiotherapy, Hadassah University Hospital Hebrew University Medical Center, 91120 - Jerusalem/IL
  • 4Department Of Human Genetics, HADASSAH-HEBREW UNIVERSITY MEDICAL CENTER, jerusalem/IL
  • 5Cga- Galil Genetic Analysis And Migal- Galilee Bio- Technology Center, CGA- GALIL GENETIC ANALYSIS AND MIGAL- GALILEE BIO- TECHNOLOGY CENTER, galil/IL
  • 6Hadassah University HospitalHebrew University Medical Center, IL-91120 - Jerusalem/IL



Inherited mutations in the breast cancer susceptibility genes (BRCA1 and BRCA2) are associated with a high risk of developing breast (BC) and ovarian cancers (OC) in females of different age and ethnic groups. The spectrum of mutations in these genes varies between populations, with some showing a high frequency of unique mutations. Ashkenazi Jews have a high rate of founder mutations in BRCA1/2, in some other Jewish communities in Israel (Jews who immigrated to Israel from Iraq, Iran and Yemen), other founder mutations had been identified. Still high proportions of Israeli BC cases with strong family history have none of the known mutations at the BRCA1/2 genes.

Methods and patients

Over 3000 breast cancer patients were evaluated in the oncogentic clinic during 1997-2011. One hundred thirty seven of them underwent full sequencing of the BRCA1/2 genes due to strong family history of breast and/or ovarian cancer or young age at presentation. Clinical and pathological characteristics of these patients were evaluated.


Sixty seven percent were non Ashkenazi Jews, Mean age at BC onset was 44 (22-77). In 20 patient (15%) BRCA 1(N = 8) or 2 (N = 12) mutations were identified. Three of the carriers had bilateral BC and 5 had OC as second primary .17 were of non Ashkenazi origin. Ninety five percent of the carriers had first degree family history of breast or ovarian cancer. The pathological information was available in half of the carriers. All had high grade (2-3) tumor, 90% of them were HER2 negative and 60% ER positive. Age at presentation had no effect on BRCA1/2 status. BRCAPRO is a predictive model to assess BRCA status and has assessed in 9 carriers, in 6 of them, the probability was >80% and in one - 5%.


A full sequence of the BRCA1/2 genes was performed in a selected group pf BC patient, who were negative for the common founder mutation in Israel. Fifteen percent were found to carry other BRCA1/2 mutations. We recommend that, patients with the following clinical features: Sephardic origin, first degree family history of BC or OC, high grade tumor, HER-2 negative, should be offered full BRCA1/2 testing. The role of BRCAPRO and other predictive model should be further evaluated.


All authors have declared no conflicts of interest.