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Not All Women at Higher Risk in Families Carrying Breast Cancer Gene
Date:10/31/2011

By Kathleen Doheny
HealthDay Reporter

MONDAY, Oct. 31 (HealthDay News) -- Women who have a relative with breast cancer linked to the high-risk BRCA genetic mutation understandably worry about their own risk.

Now, a new study suggests that women who don't test positive for the mutations are not at an extremely high risk of getting breast cancer, even if they have a relative with BRCA-related breast cancer.

Their risk is similar to that of women with relatives with non-BRCA-related cancers, the new research indicates.

This refutes a finding from a 2007 study, which found a two- to five-times higher risk for these women, even if they tested negative for the mutations, said senior study author Dr. Alice S. Whittemore, a professor of health research and policy at Stanford University School of Medicine.

Based on the new research, she said, the bottom line is this: "If you are in a family where there is a BRCA mutation and you do not have that mutation, your risk of breast cancer is no greater than anyone with a family history of [other types of] breast cancer."

According to the American Cancer Society, having one first-degree relative, such as a mother, sister or daughter, with breast cancer doubles a woman's risk of getting it. Having two close relatives increases the risk about threefold.

Whittemore calls the new finding "very, very reassuring" because it suggests that having a family history of the BRCA mutation, by itself, is not a risk factor, she said.

The study is published online Oct. 31 in the Journal of Clinical Oncology.

Women with a BRCA1 or BRCA 2 gene mutation have a 5- to 20-fold higher risk of getting breast or ovarian cancer, the Stanford researchers wrote. That means a lifetime probability of up to 65 percent for breast cancer, and up to 40 percent for ovarian cancer.

Women who have the BRCA1 and BRCA2 mutations and are cancer-free are urged to step up their screening and to begin it early, by age 25, among other measures. They may also consider a preventive mastectomy or ovary removal after childbearing is done.

However, the 2007 study, Whittemore said, "sent an alarm signal to the medical community" as it suggested a high risk even in BRCA-negative relatives.

After the study was published, she and her colleagues took a closer look. "What we thought to be the flaw was that they were comparing these relatives of women with breast cancer to the general population. A better comparison group would have been women who have relatives with breast cancer but no mutation," Whittemore said. "That's what we did."

The new study looked at 3,047 families from the United States, Australia and Canada. It included 160 families with BRCA1 and 132 with BRCA 2. The researchers compared cancer risk in women who tested negative but had relatives with BRCA-related breast cancer with a group of cancer-free women who had relatives with cancer that wasn't BRCA-related.

They found no increased risk for the women who were BRCA-negative and had close relatives with BRCA-related cancer.

In other words, Whittemore said, their risk is "no greater than anybody with a family history."

Besides BRCA1 and BRCA2 mutations, other risk factors, not totally understood, that can run in families also drive breast cancer risk, experts say. One example is drinking habits.

The findings suggest that BRCA-negative women can follow the same breast cancer screening routine as the general population, if they have no other strong risk factors, Whittemore said.

The findings should be reassuring to women without the mutation, agreed Dr. Patricia Ganz, director of cancer prevention and control research at the University of California's Jonsson Comprehensive Cancer Center.

The results do suggest that women in a family where BRCA-related breast cancer had occurred who themselves are negative for BRCA mutation may have a slightly increased risk "because there are other things that influence getting breast cancer besides having the gene mutation," she said.

"The main message," she said, "is that these women [without the mutation] don't need all that extra surveillance."

Testing for BRCA mutations requires a sample of blood or cells be taken from the mouth, said Rebecca Chambers, a spokeswoman for Myriad Genetics, which provides the test.

The samples can be collected at any lab and mailed in for analysis. The test costs $3,340, she said, but the average out-of -pocket cost is $100 after insurance coverage.

More information

For more on BRCA mutations, go to U.S. National Cancer Institute.

SOURCES: Alice S. Whittemore, Ph.D., professor, health research and policy, Stanford University School of Medicine, Stanford, Calif.; Patricia Ganz, M.D., director, cancer prevention and control research, Jonsson Comprehensive Cancer Center, University of California Los Angeles; Rebecca Chambers, spokesperson, Myriad Genetics, Salt Lake City, Utah; Oct. 31, 2011, Journal of Clinical Oncology, online


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