Simple, fast and effective method of detecting a large number of patients at high risk for hereditary breast/ovarian cancer

One in five women diagnosed with breast or ovarian cancer who seek mammography have a family history of cancer that suggests they may harbor known cancer-causing gene mutations.

Writing in the November 1, 2005 issue of CANCER, a peer-reviewed journal of the American Cancer Society, researchers say the prevalence of such a family history is considerably higher than the rate among women with no personal history of cancer, and has significant implications for risk assessment, testing, and clinical management.

Physicians are called upon to assess and stratify a patient's future risk of cancer. But with few cancer-specific protocols, effective risk measures, or easy to use predictive models, this remains a daunting, if not an untenable, responsibility.

While less than 10 percent of breast or ovarian cancers have been linked to heritable gene mutations in BRCA1 and BRCA2, women with these mutations have up to an 80 percent lifetime risk of breast cancer and up to a 40 percent lifetime risk of ovarian cancer. Identification for prevention, early diagnosis and treatment are paramount to save lives.

A thorough family history may be the most effective measure for cancer risk. Existing modeling studies report that less than 6 percent of women without a history of breast or ovarian cancer have family histories that may identify them as BRCA1/BRCA2 mutation carriers. A small study of only 50 women with a history of breast or ovarian cancer reported that 22 percent had suggestive family histories.

For the new study, researchers led by Francisco J. Dominguez, M.D. and Kevin S. Hughes, M.D. of Massachusetts General Hospital reviewed family histories of 1764 women diagnosed with breast or ovarian cancer. The data was then analyzed according to a risk assessment protocol, the Myriad Mutation Prevalence Tables, to identify women with a 10 percent or greater risk of having mutations.

Using this tool, they found that 20 percent of women with these cancers had a 10 percent or greater risk of harboring the cancer causing mutations. Examination by cancer location showed that 100 percent of women with bilateral breast cancer, 35 percent of women with ovarian cancer, and 18.9 percent of women with unilateral breast cancer had a 10 percent or greater risk of oncogenic mutations.

More women of Ashkenazi ancestry reported high-risk family histories (47 percent) compared to women of non-Ashkenazi ancestry (18 percent).

The Myriad Tables effectively assess risk for BRCA1 and BRCA2 mutations in women using a thorough family history. "We have developed," conclude the authors, "a simple, fast and effective method of detecting a large number of patients at high risk for hereditary breast/ovarian cancer syndrome in a mammography population."