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Clinical management of BRCA1 and BRCA2 mutation carriers

Nature Clinical Practice Oncology volume 3, pages 2–3 (2006)Cite this article

More than a decade has passed since the cancer predisposition genes BRCA1 and BRCA2 were identified. Collectively, these genes appear to be responsible for cancer predisposition in virtually all families with hereditary breast/ovarian cancer, and a smaller subset of families with hereditary site-specific breast cancer. Fortunately, effective strategies have been developed to reduce the risk of breast and ovarian cancer in women with BRCA1/2 mutations, making genetic testing for these mutations an important part of the management of women with a strong family history of these diseases. Here we review the current evidence for risk reduction strategies and outline future research directions.

We and others have shown conclusively that prophylactic oophorectomy in women with BRCA1/2 mutations reduces the risk of ovarian cancer by approximately 90%.1,2 Although the timing of this procedure (i.e. waiting until childbearing is complete), the induction of surgical menopause, and the small residual risk of primary peritoneal cancer following oophorectomy are important considerations, oophorectomy is the single most important intervention available to BRCA1/2 mutation carriers—particularly as no effective ovarian cancer screening exists. The use of oral contraceptive pills (OCP) for chemoprevention of ovarian cancer appears to decrease the risk of ovarian cancer by 50%,3 but might be associated with a modest increase in breast cancer risk, particularly in those who used OCP prior to 1975.4 Given the excess mortality associated with ovarian cancer compared with breast cancer, a reasonable risk reduction strategy is OCP use prior to childbearing (although further data are needed in this area), consideration of transvaginal ultrasound and serial CA-125 measurements once or twice yearly after the age of 30, and oophorectomy once childbearing is complete (optimally before the age of 40).

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Author information

Authors and Affiliations

  1. Cancer Risk Evaluation Program,

    Susan M Domchek & Katrina Armstrong

  2. Abramson Cancer Center at the University of Pennsylvania, Philadelphia, PA, USA

    Susan M Domchek & Katrina Armstrong

  3. Translational Medicine and Genetics at GlaxoSmithKline, Philadelphia, PA, USA

    Barbara L Weber

Authors
  1. Susan M Domchek
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  2. Katrina Armstrong
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  3. Barbara L Weber
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Corresponding author

Correspondence to Susan M Domchek.

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The authors declare no competing financial interests.

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Domchek, S., Armstrong, K. & Weber, B. Clinical management of BRCA1 and BRCA2 mutation carriers. Nat Rev Clin Oncol 3, 2–3 (2006). https://doi.org/10.1038/ncponc0384

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  • DOI: https://doi.org/10.1038/ncponc0384

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