Breast Cancer Research and Treatment

, Volume 132, Issue 2, pp 669–673 | Cite as

Phenocopy breast cancer rates in Israeli BRCA1 BRCA2 mutation carrier families: is the risk increased in non-carriers?

  • Shiri Bernholtz
  • Yael Laitman
  • Bella Kaufman
  • Shnai Shimon-Paluch
  • Eitan Friedman


BRCA1 and BRCA2 mutation carriers have an increased risk for developing breast (and ovarian) cancer. Non-carriers from within such families (=true negatives) are counseled that their risk for developing breast cancer is similar to that of the average-risk population. Breast cancer diagnosed in a non-carrier from a family with a known mutation is coined phenocopy. The rate of breast cancer phenocopy and the risk for breast cancer in true negatives are unsettled. The rate of phenocopy breast cancer was assessed in non-carriers from Jewish families with a BRCA1 or BRCA2 mutation, identified at the Sheba medical center. Analysis was performed by t test for comparison of mean age at counseling or breast cancer diagnosis, and by calculating a standardized incidence ratio (SIR). Overall, 1318 females from 884 mutation carrying families (620 with BRCA1 264 with BRCA2 mutations) were genotyped, of whom 307 women from 245 families were assigned a true negative status (mean age at counseling 43.01 ± 13.03 years (range 19.7–92.8 years). Of these true negatives, 20 women (6.51–2.26% of families) developed breast cancer at a mean age of 54.1 ± 12.9 years (range 48.1 –60.1 years). The SIR for breast cancer in true negatives was not significantly different than the expected in the average-risk Israeli population [observed 20-expected 23.8 cases SIR = 0.84, 95% CI (0.51, 1.30)]. The rate of phenocopy breast cancer in non-carriers from Israeli BRCA1 BRCA2 mutation carrier families is 2.26% with no increased breast cancer risk over the average-risk population.


BRCA1BRCA2 mutations Breast cancer risk True negatives Phenocopy 



This study was sponsored by a grant from the Israel cancer association to the Israeli inherited breast cancer consortium. The Israel Cancer Association, a non-profit organization, sponsored a supplementary salary to Shiri Bernholtz. All other co-authors declare that they have no financial ties with the Israel Cancer Association, the organization that sponsored the research.

Conflict of interest

All authors declare that they have no conflict of interest regarding the data published herein.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Shiri Bernholtz
    • 1
  • Yael Laitman
    • 1
  • Bella Kaufman
    • 2
    • 3
  • Shnai Shimon-Paluch
    • 2
  • Eitan Friedman
    • 1
    • 3
  1. 1.The Susanne Levy Gertner Oncogenetics UnitThe Danek Gertner Institute of Genetics, Chaim Sheba Medical CenterTel-HashomerIsrael
  2. 2.The Breast Cancer Unit, Institute of OncologyChaim Sheba Medical CenterTel-HashomerIsrael
  3. 3.The Sackler School of MedicineTel-Aviv UniversityRamat AvivIsrael

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