Breast Cancer & Genes: Assessing Risk
Study Questions Accuracy of Genetic Risk Models Used to Determine Testing
The study challenges the accuracy of models used to determine who should be
offered testing for the breast cancer gene mutation BRCA, finding the
models to be poor predictors of risk for women with few female relatives over
the age of 45.
The models assess risk based on known family history of breast cancer.
"You have to have a family to have a family history," researcher
Jeffrey Weitzel, MD, of the City of Hope Cancer Center in Duarte, Calif., tells
He added that women with few older female relatives on either their mother's
or father's sides were not well served by the available models.
Inherited gene mutations play a role in about 5% of all breast cancers. But
women with BRCA1 or BRCA2 mutations have about a 50% to 85% lifetime risk of
developing the disease, compared with a roughly 10% lifetime risk among the
general population of women.
BRCAcarriers are also much more likely to develop breast cancers before the
age of 50, and their risk for ovarian cancer is also greatly increased.
Identifying women with BRCA mutations is a proven strategy for reducing the
risk of death from breast or ovarian cancer. But since the mutations are rare,
testing all women or even testing all breast cancer patients may not be
Most women who develop breast cancer before the age of 40 are considered for
genetic testing, but clinicians often rely on the prediction models to
determine whether women diagnosed in their 40s should be screened if they have
no known family link to the disease.
Weitzel and colleagues assessed the accuracy of the prediction models in
their study appearing in the June 20 issue of TheJournal of the
American Medical Association.
A total of 1,543 breast cancer patients enrolled in a cancer registry
between 1997 and 2007 were included in the study. Of these patients, 306 were
diagnosed before age 50 and reported no known first- or second-degree relatives
with breast or ovarian cancers.
When these women were questioned further about their family history, half of
them (153) were determined by researchers to have too few close female
relatives to accurately assess risk, defined as fewer than two females
relatives age 45 or older on both their mother's and father's sides of the
Genetic testing revealed that these women had a 14% risk of having a
mutation, compared with a 5% risk among women with a larger number of female
relatives who survived to their mid-40s without developing breast cancer.
"The likelihood of finding a mutation was almost three times greater
[among the women with fewer older female relatives]," Weitzel says. "We
are clearly missing women who could benefit from knowing their genetic