By Kathleen O'Neil
Young women diagnosed with breast cancer often share common worries: Could genetics be to blame for the tumor — and should they undergo testing to look for breast cancer genes?
Now certain women may have more reason to get tested, thanks to City of Hope researchers.
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, the researchers reported in the June 20 issue of the Journal of the American Medical Association.
Most physicians agree that the general, healthy population doesn’t need testing for gene mutations linked to breast cancer, including mutated BRCA genes. That’s because the risk of carrying one of these gene mutations is low — about one in 800.
These days, models used to predict a woman’s risk of having a breast cancer gene mutation rely on her family history. Experts use these models to figure out who should get tested. Some testing guidelines suggest genetic testing for women who have two or more first- or second-degree relatives (such as a mother or aunt) who were diagnosed with certain cancers.
The debate starts, though, when it comes to testing women who have no family history of breast or ovarian cancer but who develop breast cancer at an early age.
City of Hope researchers, led by Jeffrey Weitzel, M.D., director of the Department of Clinical Cancer Genetics, found that women who had early breast cancer and who had no first- or second-degree female relatives who lived past age 45 were more likely to be BRCA carriers. These female relatives could come either from the mother or father’s side of the family.
“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 more than 1,500 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 1997 and 2007.
More than 300 of these women had breast cancer before age 50 and had no first- or second-degree relatives with breast or ovarian cancers.
Half of these young women didn’t have enough older female relatives to hint at whether breast cancer gene mutations ran in their families. Here’s what’s surprising: researchers found BRCA gene mutations in nearly 14 percent of these women — significantly higher than the 5 percent who actually had a big enough family tree to determine cancer risk.
And participating women who had few female relatives who lived past 45 on one side of their family had three times the likelihood of carrying a BRCA gene mutation than did women with a big enough family tree.
“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 breast 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.
