Family History Alone Can Imply Cancer Mutation Risk

Physicians are called upon to assess and stratify a patient's futurerisk of cancer. But with few cancer-specific protocols, effective riskmeasures, or easy to use predictive models, this remains a daunting, ifnot an untenable, responsibility.

While less than 10 percent of breast or ovarian cancers havebeen linked to heritable gene mutations in BRCA1 and BRCA2, women withthese mutations have up to an 80 percent lifetime risk of breast cancerand up to a 40 percent lifetime risk of ovarian cancer. Identificationfor prevention, early diagnosis and treatment are paramount to savelives.

A thorough family history may be the most effective measure forcancer risk. Existing modeling studies report that less than 6 percentof women without a history of breast or ovarian cancer have familyhistories that may identify them as BRCA1/BRCA2 mutation carriers. Asmall study of only 50 women with a history of breast or ovarian cancerreported 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 Hospitalreviewed family histories of 1764 women diagnosed with breast orovarian cancer. The data was then analyzed according to a riskassessment protocol, the Myriad Mutation Prevalence Tables, to identifywomen with a 10 percent or greater risk of having mutations.

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

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

The Myriad Tables effectively assess risk for BRCA1 and BRCA2mutations in women using a thorough family history. "We havedeveloped," conclude the authors, "a simple, fast and effective methodof detecting a large number of patients at high risk for hereditarybreast/ovarian cancer syndrome in a mammography population."

Article: "Prevalence of Hereditary Breast/Ovarian Carcinoma Risk inPatients with a Personal History of Breast or Ovarian Carcinoma in aMammography Population," Francisco J. Dominguez, Julie L. Jones,Katherina Zabicki, Barbara L. Smith, Michele A. Gadd, Michele Specht,Daniel B. Kopans, Richard H. Moore, James S. Michaelson, and Kevin S.Hughes, CANCER; Published Online: September 26, 2005 (DOI:10.1002/cncr.21393); Print Issue Date: November 1, 2005