Screening for new breast cancer genes leaves women with tough choices

In In The News by Barbara Jacoby

Thumbnail for 8143By: Deborah Kotz


After Angelina Jolie revealed that she carried a breast cancer gene mutation last year, the number of women seeking genetic screening for breast cancer has surged — what some oncologists have referred to as the “Angelina Jolie” effect. Jolie carried a BRCA1 mutation and was told she had a 50 to 70 percent chance of developing breast cancer, a risk she deemed high enough to warrant having a preventive double mastectomy. Women with another infamous mutation, BRCA2, have a 40 to 60 percent lifetime risk of breast cancer and also frequently opt for preventive surgery.

Now, however, there are a host of more recently identified mutations that raise a woman’s breast cancer risk, though not as high as BRCA1 and BRCA2, which can make prevention choices much more complex. Should a woman have a preventive mastectomy if her lifetime breast cancer risk is 25 percent compared to the average woman’s risk of 12 percent?

One mutation called PALB2 has been associated with a 35 percent chance of developing breast cancer by age 70, according to a study published earlier this month in the New England Journal of Medicine.

“I think it takes a very detailed and nuanced discussion individualized to patients and their family history in order to really weigh the risk to benefit ratio of preventive measures,” said Dr. Huma Rana, a geneticist at the Center for Cancer Genetics and Prevention at Dana-Farber Cancer Institute. “A one size fits all approach probably won’t work for genes like this.”

Over the past year, women who undergo genetic testing for hereditary breast cancer mutations have been screened for more than a dozen gene mutations, Rana said. Many of which are “low penetrance,” meaning they’re associated with a small increase in risk that’s likely affected by other factors including family history and environmental exposures such as smoking.

Rana has personally counseled more than 10 patients at Dana-Farber over the past several months who were told they carried PALB2 mutation, and the latest finding will help her provide more information on the role the mutation plays in breast cancer risk.

“The researchers found a woman’s risk was 33 percent if she had a PALB2 mutation and no family history and was 58 percent if she had a strong family history” with two or more family members with breast cancer, said Rana, who was not involved with the study.

Those PALB2 mutations had a slightly higher risk of having “triple negative” breast cancer — a form that’s resistant to hormone treatment, more aggressive, and more likely to recur than other subtypes.

Women with high-risk mutations who decide against a preventive double mastectomy might benefit from taking anti-estrogen drugs like tamoxifen to lower their risk. They could also have extra screening. The American Cancer Society recommends that women who have a lifetime breast cancer risk of at least 20 to 25 percent have annual breast MRI screening along with mammograms; the organization recommends against MRI screening for women whose lifetime risk of breast cancer is less than 15 percent because the imaging detects a high number of false findings that turn out not to be cancer.

Dr. Anees Chagpar, the director of the breast center at Yale-New Haven Hospital who also screens patients for PALB2 and a growing number of other breast gene mutations, pointed out that quantifiying risk information on the newer mutations was limited because most of the studies include a small number of women from a specific group of families.

The researchers in the PALB2 study looked at 154 families that included 311 women and estimated that only 8 in 10,000 women carry the mutation, so finding enough women to study in the general population would be difficult.

“As we amass more and more data with thousands of women participating, we’re going to learn a lot about not only how these genes affect cancer risk but how that gene interaction plays into other factors,” Chagpar said, such as body weight, exercise habits, and alcohol consumption.

Researchers are also eager to learn more about how genes interact in non-hereditary forms of breast cancer since 90 percent of women diagnosed with the disease don’t have a hereditary type.