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BRCA Mutations Don't Spot All High-Risk Women

Family history and atypical cells also indicate high risk of second cancer, study finds,,

MONDAY, May 5 (HealthDay News) -- In women who have been diagnosed with breast cancer, having a known mutation in the BRCA 1 or 2 genes raises the risk of a second cancer, and many of these women choose to have their second breast removed before that has a chance to happen.

However, new research suggests that women who don't have these genetic mutations may still face an increased risk of a second cancer, especially if they have a family history of breast cancer or atypical breast cells.

The study involved women with a family history of breast cancer, although only some had a BRCA mutation. The researchers found that the risk of cancer in the second breast was about 10 percent, regardless of whether the woman carried a BRCA mutation or not.

The findings were slated to be presented Sunday at the American Society of Breast Surgeons' annual meeting, in New York City.

The study suggests that "we may not have identified all of the genes associated with breast cancer," according to study author Dr. Shawna Willey, director of the Betty Lou Ourisman Breast Health Center at the Lombardi Cancer Center at Georgetown University in Washington D.C.

Many high-risk women may not be advised to have a prophylactic mastectomy even though it could be potentially lifesaving, she added.

"Having a prophylactic mastectomy should not be a knee-jerk reaction to a diagnosis of breast cancer. Women need to consider this data, as well as other data, and decide whether or not this is a measure they want to take," advised Willey. She said the findings may also add to the debate about which breast cancer patients should have sentinel lymph node biopsies.

"Prevention of secondary breast cancer is becoming increasingly important," said Dr. Julia Smith, director of the Lynne Cohen Breast Cancer Preventative Care Program at the New York University Cancer Institute in New York City. "Because of advances in treatment, it's possible that many younger women with breast cancer may live for decades, so we have to focus on what we can do to prevent a further problem."

And, she said, many of the effective chemotherapy drugs can't be used a second time because they may be too toxic to healthy cells if given repeatedly, and cancer cells can become resistant to some forms of chemotherapy.

"We use our best treatment at the time to try to ensure long-term survival, but if another breast cancer comes along, we may be limited," she said.

While women with BRCA mutations are known to have a higher risk of developing an additional cancer, Willey and her colleagues wanted to learn if women with a family history but no known BRCA mutations carried a similar risk.

The analysis included 119 women who were part of the Familial Cancer Registry. All of the women had been diagnosed with an initial breast cancer, and had decided to prophylactically remove the second breast.

When the researchers analyzed the breast tissue from the second breast, they found cancer about 10 percent of the time, regardless of whether or not a woman had a BRCA mutation.

If the normal breast cancer cells were atypical -- meaning they showed precancerous changes -- the risk of breast cancer jumped to about 50 percent over a lifetime for a woman with a family history of the disease, according to Willey.

"Not having a BRCA mutation doesn't let you off the hook," Smith noted.

"There's no question that family history is extremely important. Even without a BRCA mutation, we counsel women to consider prophylactic mastectomy if they have a strong family history," she added.

More information

To learn more about prophylactic mastectomy, visit the National Cancer Institute.

Sources: Shawna Willey, M.D., director, Betty Lou Ourisman Breast Health Center, Lombardi Cancer Center, Georgetown University Hospital, Washington D.C.; Julia Smith, M.D., director, Lynne Cohen Breast Cancer Preventative Care Program, and director, Breast Cancer Screening and Prevention Program, New York University Cancer Institute and Bellevue Hospital, New York City; May 4, 2008, presentation, American Society of Breast Surgeons' annual meeting, New York City

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