AS SEEN IN USA TODAY LIFE SECTION, MONDAY, NOVEMBER 10, 2003, PAGE 5D

New agony over breast cancer
Genetic studies raise fears among Jewish women
By Rita Rubin, USA TODAY

Women dread breast cancer perhaps more than any disease, and news coverage about the latest study of breast cancer genetics ratcheted up that anxiety a notch or two.

Scientists reported that Jewish women with little family history of the disease could be carrying a genetic mutation that virtually assures they'll get it. As a result, some healthy women -- Jewish and non-Jewish -- with no relatives who have had breast cancer are wondering whether they might be carriers. Despite appearances, though, only 5% to 10% of the 211,000 breast cancer cases that will be diagnosed in the USA this year will arise from an inherited mutation.

About one out of 40 Jews of eastern European descent are thought to carry a mutation in one of the two known breast cancer genes, BRCA1 and BRCA2. In the general U.S. population, only one in 800 to one in 400 people carry a mutation in either of the genes, which also raises the risk of ovarian cancer.
The new study, which is published in the Oct. 24 issue of Science, focused on breast cancer patients who, like most American Jews, were of Ashkenazi, or eastern European, descent. If they carried a mutation, researchers tested as many of their adult relatives as possible. Carriers' offspring have a 50-50 chance of inheriting the mutation.
Half of the 104 patients with mutations had no breast or ovarian cancer among mothers, sisters, grandmothers or aunts. In nearly all of these cases, the patients had inherited mutations from their fathers, and breast cancer is rare in men. Often, their sisters and aunts had won the genetic coin toss and inherited normal versions of BRCA1 and BRCA2.

The researchers found that women with a BRCA1 or BRCA2 mutation have more than an 80% lifetime chance of developing the disease. They also have a high lifetime risk of developing ovarian cancer: 23% with a BRCA2 mutation, 54% with BRCA1. And, the scientists say, breast cancer risk in non-Jewish carriers of BRCA mutations is equally high.

"For women, that's scary, even if the reality is it probably doesn't apply to them," says Rochelle Shoretz, founder of Sharsheret, a national organization for young Jewish women dealing with breast cancer.

Worried callers

Shoretz, 31, who was diagnosed with breast cancer at 28, says she has been receiving a number of calls because of the latest study. Some callers are Jewish and some aren't, but all either know they are carriers or are worried they might be.

"We know that you can be at a higher risk even with a lower family history, and that's something that really wasn't considered before," says study co-author Jessica Mandell, a genetics counselor and research coordinator at Sara Lawrence College and the University of Washington. In breast cancer patients of any ethnic background, Mandell says, the younger they are, the greater the chance that an inherited mutation might be involved.

Shoretz sought testing right after her diagnosis, even though only her father's mother had had the disease, and it was found when she was much older. If Shoretz was a carrier, she planned to have a double mastectomy. Even healthy carriers sometimes choose to have their breasts and ovaries removed to cut their cancer risk.

"I ultimately tested negative, which was a little bit of a surprise to me," says Shoretz, of Teaneck, N.J. So she had a lumpectomy.

Although the new study doesn't discuss testing all Ashkenazi Jewish women for BRCA mutations, an accompanying editorial in the journal does raise that possibility.

Georgetown University Hospital genetics counselor Beth Peshkin says the new study drove dozens of Jewish women with little family history to call the referral line for breast cancer genetics research at her institution.

"If this provides the impetus for people to collect their family history and to make a call to get more information, then that's a good thing," she says. "My hope is that not everybody runs out and gets tested."

There's a danger that testing negative for a BRCA mutation will give women a false sense of security, Peshkin says. Women with a negative test still have the same one-in-eight lifetime risk as the general population -- perhaps even higher if they have a family history.

Screening isn't so simple

Breast cancer genetics researchers have focused on Ashkenazi Jews because nearly all of their inherited breast cancer cases arise from one of three ancient "founder" mutations, two in BRCA1 and one in BRCA2. In most other women, though, inherited breast cancers stem from BRCA1 or BRCA2 mutations unique to a family. So far, hundreds of different mutations have been identified. Theoretically, there could be thousands.

"The question of screening is not realistic for American women generally," says University of Washington geneticist Mary-Claire King, lead author of the recent study. "It's too expensive. There's too much chance a mutation would be missed."

Though the test for the Ashkenazi mutations costs a few hundred dollars, the test for mutations in the entire BRCA1 and BRCA2 genes costs nearly $3,000. Insurance usually covers the cost in women who have an elevated risk of being carriers.

Even among Ashkenazi women whose family history suggests a high likelihood of a mutation, many decide not to get tested, says Kenneth Offit of Memorial Sloan-Kettering Cancer Center in New York.

"The major barrier for women in our clinic to be tested is not the cost, is not the uncertainty, is not the fear of interventions," says Offit, discoverer of the most common Ashkenazi mutation. They're worried they'll lose their health insurance, although none tested at his clinic has, he says.

To help assuage Americans' concerns, the Senate passed a bill last month that would prohibit insurance companies from using genetic information or family histories to deny coverage or set premiums. The measure also would prohibit employers from using such information in hiring or firing. The health insurance industry has argued that the legislation would increase costs without improving consumer protection.