By Kathleen O'Neil
Women who have breast cancer before age 50 and who have few female relatives on one side of their family tree should be considered candidates for testing for cancer genes, say a team of researchers at City of Hope.
The team’s research challenges the accuracy of some breast cancer prediction models that ignore family structure. Findings appeared in the June 20 issue of the Journal of the American Medical Association.
Most physicians agree that genetic testing for gene mutations linked to breast cancer, including mutated BRCA genes, is not recommended for the general, healthy population, since the risk of carrying such a gene is low — about one in 800.
Predictive models currently used to estimate a woman’s likelihood of a breast cancer gene mutation rely on family history. Experts use these models to determine who should receive genetic testing.
Some testing guidelines suggest genetic testing in women with two or more first- or second-degree relatives with related cancers. Opinions differ, though, over recommending testing for women with no family history of breast or ovarian cancer but who develop breast cancer at an early age.
The researchers, led by Jeffrey Weitzel, M.D., director of the Department of Clinical Cancer Genetics at City of Hope, found that women who had early breast cancer and no first- or second-degree female relative who lived past age 45 on either their mother or father's side were more likely to be BRCA carriers.
“Genetic testing may be a valuable tool for women with early onset breast cancer to determine if a BRCA mutation contributed to their cancer,” Weitzel said. “Armed with that knowledge, they can take steps to prevent second occurrences of breast cancer or ovarian cancer.”
The study included 1,543 women seen at the City of Hope Cancer Screening & Prevention Program Network high-risk clinics for genetic cancer risk assessment and BRCA gene testing between April 1997 and February 2007. Of these women, 306 had breast cancer before age 50 and no first- or second-degree relatives with breast or ovarian cancers.
In 153 cases (50 percent), the patients did not have enough older female relatives to indicate there may be a breast cancer gene trait in their families. BRCA gene mutations were detected in nearly 14 percent of participants with a limited family tree, compared to more than 5 percent in women with a big enough family tree to determine cancer risk. Participants with few female relatives who lived past 45 on one side of their family had a three-fold greater likelihood of being found to be carriers of a BRCA gene mutation than those with adequate family structure.
“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,” the researchers wrote.
Mutations in the BRCA genes have been linked to increased risk of breast, ovarian and fallopian tube cancer in women and possibly prostate cancer in men. Women with mutations in the BRCA1 or BRCA2 genes who do not take preventive measures have up to a 40 percent risk of having breast cancer develop in the opposite breast within 10 years of the first cancer, researchers have found.
Genetic testing helps women determine their relative risk of cancer so they can consider preventive measures such as taking estrogen suppressing medicines (such as tamoxifen), having a preventive mastectomy or having their ovaries removed before cancer develops. Women with cancer-linked BRCA mutations also can take steps to increase monitoring for breast cancer, such as undergoing more frequent mammograms or using more sensitive technology such as magnetic resonance imaging, researchers said.
Weitzel hopes study results will change the understanding of who should receive genetic testing, especially among primary care physicians who may not ask about relatives with cancer beyond two generations.
The National Institutes of Health and the California Cancer Research Program of the University of California supported the research.