Breast cancer risk high in women with family history but no BRCA mutations

NEW YORK (Reuters Health) - Women with a significant family history of breast cancer but without BRCA1 or BRCA2 mutations have approximately a fourfold increased risk of developing the disease, study findings suggest.

Dr. Steven Narod from the University of Toronto reported the findings Monday at the American Association for Cancer Research's Seventh Annual International Conference on Frontiers in Cancer Prevention Research in Washington, D.C.

"In clinical practice we often see families with a significant history of breast cancer and negative BRCA1 and BRCA2 tests, and it is often difficult to counsel them about their risk without this information," Dr. Narod said in a written statement.

"Now when we see families such as this, we will be able to offer better advice about their actual risk. It is clear to me that the risk is high enough that we need to discuss options such as breast MRI for screening and chemoprevention with tamoxifen or raloxifene," he added.

Dr. Narod and colleagues studied 1,492 women from 365 families without BRCA1 and BRCA2 mutations but with a significant family history of breast cancer, which they defined as having two or more cases of breast cancer among close relatives under the age of 50 or three cases among close relatives of any age.

During a minimum of 5 years of follow up, 65 women developed breast cancer, compared with 15.2 expected cases, based on rates in Canadian cancer registries. This translates into a "relative risk of roughly 400% or roughly 4.3-fold," Dr. Narod reported at the conference.

The relative risk was highest in women younger than age 40, in whom the standardized incidence ratio was 14.9. The risk decreased with increasing age.

However, the absolute risk of breast cancer was higher for women between age 50 and 70 years (1% per year) than for women between the ages of 30 and 50 (0.4% per year). "This translates into about a 40% lifetime risk of breast cancer in these women," Dr. Narod said.

In this group of women with a family history of breast cancer who are negative for BRCA1 or BRCA2 mutations, "the risk of breast cancer was surprisingly high, so I think we need to confirm that in other studies," he added.

"We don't think the risk is high enough to recommend surgery," Dr. Narod said, "although some women choose to deal with it by preventive surgery of the breast. But certainly we think it's high enough that we should think about reducing it. We can do this with tamoxifen...or raloxifene."

Magnetic resonance imaging is also an option, he said. "The American Cancer Society now recommends MRI screening at a level of risk of 20% to 25%, so every woman in this study would qualify by that recommendation for an annual screening with MRI, which we and others have shown is a much more sensitive preventive measure than standard mammography," Dr. Narod noted.

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