Breast Cancer And Family Relations – Large and Small Family and History of the Disease

Breast Cancer And Family Relations – Large and Small Family and History of the Disease

X-Ray

(Best Syndication) Researchers say that current models used to predict a woman's risk of breast cancer may be flawed. They found that the probability of the breast cancer gene mutation BRCA among women with a history of breast cancer is greater when the number of older, female relatives in the family is smaller.

Jeffrey N. Weitzel, M.D., of the City of Hope, Duarte, Calif., and colleagues conducted the research. They wanted to determine if genetic risk models underestimate the BRCA gene mutation prevalence for “single-case indicators,” that is women with a limited family structure (less than two females who lived to age 45 or older in each lineage) who have early onset breast cancer and no family history of breast or ovarian cancers.

The new research appears in the June 20 issue of the Journal of the American Medical Association (JAMA). “If true, a more accurate estimation of BRCA gene mutation probability may be needed for these women,” the researchers wrote.

The study involved 1,543 women seen at U.S. high-risk clinics for genetic cancer risk assessment and BRCA gene testing. These women were enrolled in the study between April 1997 and February 2007. Of these women, 306 had breast cancer before age 50 years and no first or second degree relatives with breast or ovarian cancers.

The researchers said that family structure was limited in 153 cases (50 percent). The BRCA gene mutation was detected in 13.7 percent of participants with limited vs. 5.2 percent with adequate family structure. They found that participants with a limited family structure had an increased likelihood of being carriers of a BRCA gene mutation than those with adequate family structure.

“Germline BRCA1 or BRCA2 gene mutations significantly increase a woman’s risk of breast cancer (50 percent - 85 percent) and ovarian cancer (16 percent - 50 percent),” the authors wrote. “Documented efficacy of screening and risk reduction interventions provides evidence for individualized risk management advice, making genetic cancer risk assessment (GCRA) a component of medically necessary care. Identifying appropriate candidates for GCRA is challenging.”

“Although statistically intuitive, limited family structure is akin to the problem of ‘missing values’ and is a limitation of all common mutation probability models. Consequently, absent better models, cancer risk assessment practices and genetic testing guidelines need to be more inclusive of single cases of breast cancer when there is limited family structure,” the authors wrote. “The fact that commonly used models for estimating BRCA gene mutation probability were insensitive to family structure as a predictive factor is a cautionary note for community practitioners.”

“Given the significant effect of family structure, illustrated by limited accuracy of probability models for single cases of breast cancer, and the commonality of the missing-data problem, the databases of currently available probability models should be reanalyzed and limited family history recoded as a separate variable.”

Back in 1998 researchers at the Fred Hutchinson Cancer Research Center, Seattle, Washington (published in the JAMA) believed that in 5% of breast cancer cases, there was a strong inherited familial risk. Two autosomal dominant genes, BRCA1 and BRCA2, account for most of the cases of familial breast cancer. Family members who harbor mutations in these genes have a 60% to 80% risk of developing breast cancer in their lifetimes.

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By Jeffrey Workman
Best Syndicaiton News Health Writer

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