African American women are less likely to be diagnosed with breast cancer than white women, yet are more likely to die of the disease.
To some degree, this disturbing disparity reflects differences in patterns of care, which may involve socioeconomic factors. Studies show that black women tend to be diagnosed at a later stage and often have trouble accessing treatment.
But that doesn't fully explain the racial survival imbalance, so increasingly, researchers are looking for biological differences.
Now, a study by the Moffitt Cancer Center in Tampa suggests premenopausal African American breast cancer survivors are more likely than their white counterparts to have defects in BRCA1 and BRCA2, genes that normally suppress tumors by repairing damaged DNA.
How much more likely? The researchers found that 12.4 percent of black breast cancer survivors under age 51 had BRCA mutations - twice the estimated 6 percent rate for premenopausal white women.
Overall, about 5 percent of all breast cancer patients, and 15 percent with ovarian cancer, have mutations that knock out the cancer-fighting function of BRCA1/2. However, people of Eastern European Jewish ancestry have the highest-known incidence of BRCA mutations - about 1 in 40 people, tenfold higher than other populations.
The new finding, published in August in the journal Cancer, comes with caveats. Lead author Tuya Pal, a clinical geneticist at Moffitt, said it needed to be validated by other studies. And though the Moffitt study was the largest to date of premenopausal black breast cancer survivors, the results may be skewed by the sampling process; only 396 of 882 survivors who were recruited through a Florida cancer registry completed the genetic testing. Of those 396, 49 had BRCA mutations.
"Studies show that the people more likely to come on these studies are people more likely to be worried about genetic risk," said oncologist Susan Domchek, who heads the Basser Research Center for BRCA at the University of Pennsylvania.
Even so, Domchek said her own research also pointed to a higher mutation rate among black women compared with white women.
Harvard University epidemiologist Timothy Rebbeck, formerly of the Basser Center, said small studies had also found high BRCA mutation frequencies in black breast cancer patients in Nigeria and the Bahamas.
Adding to this genetic puzzle, African American women are known to be disproportionately affected by breast cancer subtypes that are aggressive. One subtype, known as "triple negative," often develops in premenopausal women and doesn't respond to targeted treatments.
"How much of that is due to BRCA mutations?" Rebbeck asked. "We don't know."
Another question is how to improve black women's access to genetic counseling and testing - especially as professional medical guidelines and insurance coverage vary.
Because the women in Pal's study were 50 or younger at diagnosis, all of them met one set of national guidelines, from the National Comprehensive Cancer Network, for referral for genetic counseling. Yet only 35 percent actually were referred by their doctors for testing after being diagnosed with breast cancer.
The researchers also found many women in the study with BRCA mutations had no close relatives with breast or ovarian cancer, so they would have been ineligible for BRCA testing under current guidelines. That's why Pal and her coauthors advocate a controversial idea: Test all black women diagnosed with breast cancer before age 51, regardless of family history.
"We know that there are disparities in testing among black women and agree that it's important to increase access to genetic counseling and testing," said Lisa Schlager, a vice president of FORCE (Facing Our Risk of Cancer Empowered), a Tampa nonprofit devoted to people with BRCA mutations.
Kwame Williams, 43, of Philadelphia, knew she was at risk of breast cancer because the disease killed her grandmother and mother - the latter at 52. Williams began getting annual mammograms when she was only 28.
Still, it wasn't until last year, when the elementary school principal was diagnosed with an aggressive breast cancer, that her oncologist recommended BRCA testing.
After a BRCA2 mutation was identified, Williams opted for a double mastectomy followed by reconstruction, and a complete hysterectomy.
"I might not have known about the need to get the genetic testing" if her oncologist had not suggested it, she said.
But Williams' experience also illustrates a fundamental dilemma: Science has made little progress in preventing BRCA-related cancers, or in identifying who will beat their genetic odds. Removing healthy organs remains the most effective self-protection strategy.
"These are very severe interventions," said Rebbeck at Harvard. "It's not just taking a pill that has minor side effects. There is a lot of debate about population-wide testing. I don't think we're there yet with African Americans. You'd really want to have better data on risks before you say, 'Test everybody.' "