June 19, 2007 -- When you're filling out your family history at a new doctor's office, you probably list things like your dad's heart attack and your grandmother's stroke.
It's a wise move, considering that family history plays a big part in your risk for certain diseases. But now medical genetics experts are asking: What about the relatives you never had?
A team led by Dr. Jeffrey Weitzel of the California-based City of Hope cancer hospital has found that some women with breast cancer had inherited genes that put them at a greater risk for the disease -- but because they had few female relatives, they did not have a family history of the disease to act as an early warning.
When Weitzel tested over 1,500 women under age 50 with breast cancer, he found about 300 who had mutations in one of the so-called BRCA genes, which increase women's risk for developing early and multiple breast and ovarian cancers.
But fully half of these women had what he called a "limited" family history for breast cancer -- less than two female relatives on either side of the family who had lived past age 45.
That is alarming, since current guidelines for testing for this deadly gene specify that the patient should have two or more relatives with related cancers. Women with smaller families sometimes don't qualify.
Thus, Weitzel's findings mean that having few female relatives, is, in a statistical sense, a risk factor for a BRCA mutation.
The study is published in the current issue of the Journal of the American Medical Association.
BRCA gene mutations don't cause cancer on their own. But inheriting the gene mutation increases risk of breast cancer by 50-85 percent. Even if the breast cancer is caught early, 25 percent of those patients will die of ovarian cancer.
Because of these sobering numbers, women who test positive often have their breasts, their ovaries or both removed. But without a mother or aunt who has been diagnosed with breast cancer, it is often less likely that a woman will even be screened for this abnormal gene.
And the mutation may even come from Dad's side of the family tree. But since breast cancers in men are very rare, it can pass silently from generation to generation until a woman inherits the gene.
"It's just pure straightforward math that 50 percent of carriers are men," Weitzel said. "If Dad didn't have sisters, there's not a chance to see [cancer] in his generation."
According to Weitzel, cancer patients who want to be tested for the deadly gene may even be denied the opportunity due to their age (frequently the patient must be younger than 40) or lack of family history for the disease.
Because of this, he said, he has seen cases where a breast cancer patient subsequently developed cancer of the other breast, or ovarian cancer -- cancer that may have been prevented with preemptive surgery.
Such cases motivated him to conduct the current study to try to prove that a 45-year-old woman with no aunts, for example, might still be positive for the ominous BRCA mutation.
"Typically, insurers require there to be at least a 10 percent likelihood of a positive test [based on existing models that use known family history] to pay for the test," Weitzel said, adding that he has advocated for the elimination of such numerical cutoffs.
"It seems wrong to go with models rather than clinical judgment."
Thousands of women are potentially affected by these policies. The BRCA mutation is responsible for 5 percent of breast cancers and almost 10 percent of ovarian cancers, says Weitzel.
Since there are nearly 270,000 new cases of breast cancer each year, that amounts to almost 13,500 women with breast cancer annually who could benefit from the test if they received it.
Dr. Noah Kauff of Memorial Sloan-Kettering Cancer Center in New York wrote an accompanying editorial to Weitzel's paper, expressing dissatisfaction with the way that computer models and formulas don't do a good job of identifying women who might have BRCA mutations.
He also points out a disconcerting fact; many current cancer patients were diagnosed before BRCA genes were even discovered in the mid-1990s.
"Patients should advocate for themselves," he said. "The oncologist might not go back and do a family history or think about the gene."
Kauff agrees with Weitzel that women without female relatives who develop breast cancer before age 50 should be tested. The 40-50 age group often "falls through the cracks," he said.
"Physicians and patients are good at identifying if there are seven people in the family with ovarian or breast cancer," Kauff said. "What they're not good at is the limited family history which could still be a source [of risk itself]."
For women significantly older, though, the experts agree that the chances of a BRCA mutation having caused a cancer are very low.
Better Family Histories, Increased Detection?
Dr. Mary Daly of Fox Chase Cancer Center, a recognized expert on BRCA genes, said the news could help patients get better care for themselves.
"One in 800 people carries the mutation," she says. "[Patients should] get as thorough a family history as they can from relatives. If they have any suspicions, they should see a genetic counselor to work out the issues.
"My grandparents are both deceased -- I wished I would have asked them more questions when I was younger."
Dr. Marisa Weiss, founder of the Web site Breastcancer.org, said, "This study is important for both sides of the patient-doctor relationship: to make sure that each patient gets the best guidance so she can take appropriate steps to reduce her risk of getting breast cancer again, as well as ovarian cancer."