Domchek SM, Gaudet MM, Stopfer JE et al.
University of Pennsylvania, Philadelphia, PA, USA.
Breast Cancer Res Treat 2010;119:409–14.
Editor’s note: An unaffected individual who undergoes testing for a BRCA1 or BRCA2 mutation that is known to exist in their family and has a negative result has long been considered “true-negative”. Unless there are other risk factors for the development of cancer present, these individuals have been counseled that they are at similar risk as the general population for both breast and ovarian cancer. The differences in these risks are significant; for example, the lifetime risk of breast cancer is 44–75% in BRCA1/2 mutation carriers and approximately 13% in the general population. Therefore, in most situations, true-negative women are counseled to follow the same screening guidelines as women in the general population. This paradigm has recently been called into question by several small studies suggesting that true-negatives may in fact be at a slightly elevated risk of breast cancer compared with the general population, with relative risks of approximately 2.0 being described. As the major benefit of genetic testing for BRCA and mutations is to identify true-negatives in order to avoid unnecessary screening and preventative interventions, a more complete analysis of this crucial issue is required. In order to address this issue, the current authors describe their experience with a large cohort of true-negative women who were prospectively followed up after receiving their negative genetic test results.