University of Virginia Health System

Experts Look Closely at Gauging Breast Cancer Risk

Current methods of gauging a woman's breast cancer risk that rely on her family history may underestimate the danger, says a study in the Journal of the American Medical Association.

Using risk assessment models helps physicians determine whether or not a woman carries the BRCA1 or BRCA2 gene mutations that would predispose her to breast cancer.

If a woman’s family history suggests she might carry such a gene, physicians can offer screening for the mutations.

The new study found that there may be a better way to refine the risk model so those predictions are more accurate.

"In some circumstances, we have to qualify what family history can tell us," says lead researcher Dr. Jeffrey Weitzel of City of Hope Comprehensive Cancer Center.

He points out that family history data is not always available to women, and "if there's no family, then you can't have a family history, if you don't have older women in either lineage."

Family Information May Be Hard to Find

Dr. Jay Brooks of Ochsner Health System, says, "We're trying to predict which women should get tested [for a genetic predisposition].

“The test is expensive, and not every woman can get it," adds Dr. Brooks. However, "with smaller families today, many times you don't have that extensive family tree that you can reconstruct.”

The implications could be lifesaving for many women. Mutations in BRCA 1 and BRCA 2, especially, can greatly increase a woman's risk of developing both breast and ovarian cancer.

"It's now medically necessary that access to care should be broader, and more people should be able to take advantage of [gene screening], because it may make a big difference in outcome," notes Dr. Weitzel.

"Failure to recognize that a woman happens to be a BRCA carrier and do appropriate prevention procedures could cost a woman her life," he says.

Although BRCA mutations are relatively rare (affecting only about 5 percent of the population), those with the misfortune to carry them have a 50 percent to 85 percent greater chance of developing breast cancer and a 16 percent to 50 percent higher risk of developing ovarian cancer.

Women with breast cancer who have a BRCA mutation also have a higher risk of developing another breast cancer or ovarian cancer. A mastectomy or oophorectomy (removal of the ovaries) can significantly reduce that risk.

Most of the methods available to estimate how likely a person is to carry the BRCA 1 or BRCA 2 defects were developed using data from large families. They incorporate information on family history, age at diagnosis, and ethnic ancestry.

It is these models that are most often used by insurance companies when deciding whether or not to pay for the gene test.

But the fact that a woman's father might have passed on the mutation is often not taken into account, explains Dr. Weitzel.

"Half of all heredity for breast cancer comes from dad," he says. "Most clinicians don't realize that BRCA can be inherited through dad."

Then there are women with early-onset breast cancer but no history of breast or ovarian cancer, or patients with less than two female relatives surviving beyond age 45 on each side of their family. The model does little to help them, experts say.

For the study, Dr. Weitzel's team combed through information on more than 1,500 women cared for at high-risk breast cancer clinics in the US.

The conclusion was that women under 50 with breast cancer and a limited family structure - less than two females age 45 or older on either side of the family - were almost three times more likely to be BRCA carriers than women with adequate family structure.

Wider Testing Supported

BRCA gene mutations were found in 13.7 percent of women with limited family structure compared with 5.2 percent of those with adequate family structure.

Dr. Weitzel now believes that "family history is not a good tool. We shouldn't discriminate against women [who have limited family structure]. What if she's adopted? We lost whole generations to the Holocaust. Why should we deny them access to testing?"

In women with little family history to rely on, age may end up being a deciding factor in assessing BRCA-linked breast cancer risk.

Women under 40 who have breast cancer are usually tested for the BRCA mutations, but women in the next decade of life probably should be as well, the researchers say.

"Most crucial is the 40-to-50 age range," says Dr. Weitzel.

"Younger women who have breast cancer, especially those below 50, really should raise a red flag about genetic testing," adds Dr. Brooks.

"Age is a very, very powerful thing. The average age for developing [breast cancer] is 60. If you're developing disease 10 years before you're expecting to, that should raise a red flag," says Dr. Brooks.

"You're trying to predict who deserves the test," he continues. "With small family numbers, we may be underestimating who needs to be tested."

Always consult your physician for more information.