Illustration: Timothy Cook
The secret within
They search for a reason, some explanation behind the disease. Many may wonder if the answer lies in their genes; but without knowing that a mother, aunt, sister or other close relative had breast cancer, they may be discouraged from undergoing genetic testing to look for so-called “breast cancer genes.”
New findings from City of Hope researchers give more women reason to look within for answers.
photo: Paula MyersJeffrey Weitzel
Health care providers should consider genetic testing for women who develop breast cancer before age 50 and who have few living female relatives on one side of their family tree, the researchers reported. Published earlier this year in the Journal of the American Medical Association, their study challenges the accuracy of some breast cancer prediction models that ignore a woman’s family structure.
Genetic testing looks for gene mutations linked to a high risk of breast cancer, including mutated BRCA genes (which also raise ovarian cancer risk). Most physicians recommend against genetic testing for the general, healthy population, since the risk of carrying such a gene is low — about one in 800.
Models used today 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 guidelines suggest genetic testing for women who have two or more first- or second-degree relatives with related cancers. Opinions differ, though, over whether to test 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’s 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 1997 and 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, or 50 percent, the patients did not have enough older female relatives to suggest inherited cancer risk. But researchers found BRCA gene mutations 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 age 45 on one side of their family were three times more likely to carry a BRCA gene mutation than were women with adequate family structure.
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 risk so they can consider preventive measures such as taking estrogen-suppressing medicines (such as tamoxifen), undergoing a preventive mastectomy, or having their ovaries removed before cancer develops. Women with these mutations also may increase monitoring for breast cancer, including undergoing more frequent mammograms or using more sensitive technology like magnetic resonance imaging, researchers said.
Weitzel hopes the 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.