Breast cancer risk models flawed, study shows

By Julie SteenhuysenWed Jun 20, 2:29 AM ET
Tools used to predict whether a woman's breast cancer is inherited do not account for smaller families and may leave some women in the dark about their risk for future cancers, U.S. researchers said on Tuesday.
"You've got to have family to have a family history of breast cancer," said Dr. Jeffrey Weitzel of the City of Hope cancer center in Duarte, California.
Weitzel said women with breast cancer are often asked if they have a family history of the disease, information that is used to decide whether they should get genetic tests to see if their cancer is inherited.
"Most of the models used to determine who might get genetic testing were based on large families and families where there were multiple cases," he said.
"But what about those women who were younger than expected when they got their cancer but who don't have a family history of cancer," asked Weitzel, whose study appears in the Journal of the American Medical Association.
While only 5 to 10 percent of breast cancer cases are inherited, women with mutations of the BRCA1 or BRCA2 gene have a much higher risk of developing another breast cancer or ovarian cancer.
And many insurance companies use these risk assessment tools to decide whether to pay for genetic tests, which cost roughly $3,000 for most women, Weitzel said.
GREATER RISK
"If a woman has limited-stage breast cancer, she's got a pretty good chance of long-term disease-free survival," Weitzel said in a telephone interview.
"However, if she carries a BRCA gene mutation, her chance of having another breast cancer is nearly 50 percent in her lifetime. It's at least 30 to 40 percent in the next 10 years after her first diagnosis. That is a big deal," he said.
To see whether risk assessment tools were underestimating the risk of some patients, Weitzel and colleagues, between 1997 and 2007, evaluated 306 women who had breast cancer before age 50.
Women with fewer than two close female relatives on either parent's side who lived past the age of 45 were considered to have a limited family structure. About half of patients fell into this group.
The study found that participants with less family information to draw from actually had a higher risk of having the BRCA gene mutation than those with larger families.
BRCA gene mutations were found in 13.7 percent of participants with limited family structure, compared with 5.2 percent with adequate family structure.
Weitzel said the findings challenge the accuracy of the probability models used to determine the need for genetic tests.
The result is important because many women with the BRCA gene mutations are followed more closely and treated more aggressively, including with drugs to prevent cancer and surgery to remove their breasts or ovaries.
"Finding out if someone is at inherited risk clearly does change how we follow people," said Dr. Noah Kauff of Memorial Sloan-Kettering Cancer Center in New York, who wrote a commentary in JAMA encouraging that doctors use these risk models with caution.
"If you have breast cancer prior to age 50 and not a lot of women on your mother's or father's side, it is probably reasonable to test" for inherited cancer, Kauff said.