Tuma, Rabiya S. PhD
It has been known that African American women with breast cancer are more likely to die of their disease than Caucasian women are. The mortality gap has been widening in the last three decades and remains even when women are treated in a clinical trial and receive the same treatment. Now, investigators reported at the American Society of Clinical Oncology Annual Meeting that more than one-fifth of African American women with breast cancer carry a deleterious mutation in a known risk gene and that most of the mutations identified were unique to individual women (Abstract CRA1501).
“This work highlights the genetic diversity in this population and emphasizes that techniques that look at only a few sites and a few genes will not be adequate for this population,” said Jane E. Churpek, MD, Assistant Professor of Medicine at the University of Chicago, who presented the work.
“Her findings regarding the frequency and nature of harmful mutations are remarkable and highlight the need for increased focus in this population that has been reported to be under-counseled as well as under-tested,” said Andrew D. Seidman, MD, an ASCO spokesperson and attending physician for the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, during a news conference in which the data were discussed.
Modern Techniques Reveal Diversity
The researchers analyzed genomic DNA from 249 unrelated African American women who were identified through the Cancer Risk Clinic at the University of Chicago. Using a technique called BROCA, which includes genomic capture and next-generation sequencing, the investigators examined a panel of 42 genes, including all 18 genes known to be associated with breast cancer. (The technique is named after Paul Broca, a French physician in the 1800s who was among the first to describe inherited breast and ovarian cancers.)
Churpek and her colleagues found that 22 percent of the women studied carried clearly deleterious mutations. Of those, 79 percent were in BRCA1 (n=26) or BRCA2 (n=20). The remaining mutations occurred in CHEK2 (n=3), PALB2 (n=3), ATM (n=5), and PTEN (n=1).
Interestingly only six of the mutations—five in BRCA1 and one in BRCA2—occurred in more than one person. The remaining mutations were unique to individuals and had not previously been identified in breast cancer patients. Researchers have seen several of the shared BRCA1 and BRCA2 mutations in African Americans previously.
When the investigators looked at risk factors associated with deleterious mutations, they found that women diagnosed at a younger age were more likely to have a mutation, particularly BRCA1. However, in this population, even women over the age of 46 at diagnosis had an approximately 10 percent risk of carrying a deleterious mutation. Additionally, women diagnosed with Grade III tumors or triple-negative disease were more likely to have mutations, with a risk between 25 and 30 percent. Those who had a second cancer had a risk of approximately 50 percent.
As expected, having a family history of breast and ovarian cancer also increased the likelihood of carrying a mutation, at approximately 30 percent. It was nearly that high for women who had a family history of pancreatic cancer, emphasizing again the importance of this tumor type in breast cancer risk assessment.
However, even 12 percent of the women who no family history of breast, ovarian, or pancreatic cancers carried a deleterious mutation—”reminding us that family history alone is not the sole criteria for predicting who will have mutations,” Churpek said during her presentation.
That fact was driven home by three individuals in the study who each carried two deleterious mutations. The mutation pairs included BRCA2 and ATM, CHEK2 and ATM, and CHEK2 and CHEK2. All three of these women were diagnosed in their early 30s, but only one had a family history.
JANE E. CHURPEK, MD
Access to Care
This population is not all that different from other breast cancer populations, noted the study's Discussant, Judy Garber, MD, MPH, Director of the Cancer Risk and Prevention Program at Dana-Farber Cancer Institute, who pointed out that the Cancer Genome Atlas study of 507 breast cancers identified mutations in approximately 10 percent of patients. “Ten to 20 percent is the number, maybe, we should keep in our heads,” she said.
While she and Churpek noted that the particulars of the data presented might not be generalizable to the whole population because the study patients came from a single urban clinic, they agree that the themes uncovered are. “These same [risk] factors should clue women into the fact that they need to be tested and we should make sure that we can provide access to all populations across the U.S. and elsewhere,” Garber said.
Churpek emphasized similar points, noting that the work underscores the need for increased access to testing and counseling for all women.
“It also shows that these new techniques that allow us to comprehensively test all of these genes, including BRCA1 and BRCA2, in a single test and a single visit, really will allow cost effective and efficient genetic testing, which is not clinically possible now. These tools will allow us to better identify who is at risk before they develop cancer and to focus on prevention, and, eventually impact public health,” she concluded.