Breast cancer risk assessment in patients who test negative for a hereditary cancer syndrome

Published:October 11, 2019DOI:


      • Lifetime breast cancer risk was calculated in mutation-negative women with a significant family history of breast cancer.
      • Over half of women with an uninformative negative genetic test result were identified as high-risk.
      • The Tyrer-Cuzick model identified the greatest proportion of high-risk women.
      • Women should not conclude that a negative genetic test result represents a lack of risk.



      The majority of women who undergo genetic testing due to a significant family history of breast cancer will receive a negative result. The purpose of this study was to calculate the lifetime risk of breast cancer in women undergoing genetic counseling who received an uninformative genetic test result.


      A retrospective chart review of mutation-negative women presenting to a cancer risk assessment clinic was performed. Lifetime risks of breast cancer were calculated using the Claus, Gail, and Tyrer-Cuzick risk assessment models.


      Approximately half (51%) of the women were classified as high-risk by at least one risk assessment model. The Tyrer-Cuzick model identified the highest proportion (43.2%) of patients as high-risk. Four percent (n = 4) of the sample was considered high-risk by all three models.


      More than half (51%) of women who underwent genetic counseling and received an uninformative negative genetic test result had a significantly elevated risk for the development of breast cancer. It is, therefore, imperative that women do not conclude that a negative genetic test result represents a lack of risk.


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      • Discussion on: Breast cancer risk assessment in patients who test negative for a hereditary cancer syndrome
        The American Journal of SurgeryVol. 219Issue 3
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          DR. STEPHANIE VALENTE (Cleveland, Ohio): As we heard, the authors evaluated 88 patients with a strong family history of breast cancer who underwent genetic testing and were negative. They used the term “uninformed result” because physicians don’t know how to properly counsel or subsequently screen a patient with a strong family history and subsequent negative genetic results. The results of the study showed that there is a patient population at significant risk for developing breast cancer and that the uninformative result patient should be further explored to identify proper individualized high risk screening plan.
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