ASCO 2013: More than 20% of African American Women Carry Inherited Mutations in at Least One Breast Cancer Susceptibility Gene
A genomic profiling study of African American women with breast cancer found that about one in five carries an inherited abnormality in at least 1 of 18 genes associated with breast cancer susceptibility. Such mutations were more prevalent among women with aggressive triple-negative breast cancer, early onset disease, and a family history of breast and ovarian cancer. The findings, presented at the 2013 ASCO Annual Meeting (Abstract CRA1501), suggest that broader genetic screening with next-generation sequencing may be beneficial for these women and their family members.
“Breast cancer survival is overall worse for African American than for white women and the disparities gap continues to widen,” said the study’s lead author, Jane E. Churpek, MD, a hematogist/oncologist and Assistant Professor of Medicine at the University of Chicago. “For those of us here in Chicago it is particularly relevant, because we have one of the worst disparities in the country.”
The study was conducted among 249 women referred for genetic counseling to the Cancer Risk Clinic at the University of Chicago. “Importantly, these women were on average 43 years when they were diagnosed, and thus are younger than the average population of breast cancer patients and at baseline had a higher chance of having an inherited mutation than the general population,” Dr. Churpek noted.
Aggressive Triple-negative Disease
Compared to other ethnic groups, African American women have increased rates of early onset and aggressive triple-negative breast cancer, as well as poorer survival once diagnosed with breast cancer. While most prior studies have focused on BRCA1 and BRCA2 gene mutations, this is the first comprehensive study among African American women of all known genes associated with breast cancer susceptibility.
Genomic DNA was extracted from peripheral blood and analyzed for the presence of mutations in 18 breast cancer susceptibility genes using an assay called BROCA, which utilizes targeted genomic capture and next-generation sequencing. Overall, 56 out of 249 patients (22%) had at least one clinically relevant mutation. Most of these women carried a single mutation.
“The majority of these did occur in BRCA1 and BRCA2, 79%,” Dr. Churpek acknowledged. “However, we also saw 21% of mutations in other genes with defined cancer risks, including ATM, CHEK2, PALB2, and PTEN.”
Mutations were most common among patients with a second primary cancer in the breast (49%), triple-negative breast cancer (30%), a family history of either breast or ovarian cancer in a close relative (30%), and patients diagnosed before the age of 45 years (27%). “Even among those who did not have a family history of breast or ovarian cancer, over 10% still carried mutations,” Dr. Churpek pointed out, “again reminding us that family history is not the only criterion that we should think of [with regard to predicting the presence of these mutations].”
Great Diversity of Mutations
“Almost all of the mutations that we identified were different, meaning that each women inherited a different mutation that was not seen in the other women,” Dr. Churpek said. “This is important because for some populations we can use tests that look at just a few sites and a few genes and we can identify the majority of mutations. But that technique will not work for this population with such great genetic diversity.
“These results argue for increased screening for mutations in African American women diagnosed with breast cancer at a younger age, with triple-negative breast cancer, and/or with a family history. Since such testing may lead to lifesaving interventions for their family members, these data underscore the need to overcome barriers to genetic testing for breast cancer risk among African American women,” said Andrew D. Seidman, MD, Attending Physician for the Breast Cancer Medicine Service at Memorial Sloan-Kettering Cancer Center, New York.
“Even in the absence of young age or triple-negative breast cancer, risk susceptibility mutations are frequent in this population and other studies previously have documented that this is a population that has been undercounseled and undertested,” Dr. Seidman added.
Next-generation Sequencing
Next-generation sequencing assays, like BROCA, allow assessment of multiple genes from multiple people at the same time, making them more efficient and cost-effective than traditional genetic screening technologies. In addition, these tools can detect all the different types of abnormalities in the genetic code, which previously required multiple methods.
The authors stated that this type of testing is clinically available and costs about the same amount as current BRCA1 and BRCA2 testing, but like all risk-related genetic testing is best performed by professionals trained in cancer risk assessment who can help individuals understand their own risk of developing cancer, what type of testing is appropriate for them, how to interpret the information each test provides, and how best to reduce their risk. Current strategies for breast cancer risk reduction and early detection for women at increased risk include preventive surgical removal of the ovaries and/or breasts, risk-reducing medications, and more intensive screening with breast MRI.
This research was supported in part by the National Institutes of Health, the Breast Cancer Research Foundation, and Komen for the Cure.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
