CHICAGO—African-American women with breast cancer referred for genetic counseling had a high number of inherited mutations in BRCA1 and BRCA2; however, 22% had mutations in other genes with well-defined, clinically meaningful, cancer susceptibilities, a study presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting has found.

This first comprehensive screen of all known breast cancer susceptibility genes among African American women using next generation sequencing underscores the need to provide wider access to genetic counseling and genetic testing services, especially in previously underserved populations, said Jane E. Churpek, MD, Assistant Professor of Medicine at The University of Chicago, Chicago, IL.

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.

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“For many years, we’ve seen breast cancer take a heavy toll on African-American women, and this study begins to resolve unanswered questions about what’s driving these disparities,” said Dr. Churpek. “While larger studies are needed to confirm our results and compare them to other populations, we hope our findings will lead to increased awareness about potentially life-saving genetic screening for African-American women with a personal or family history of early onset or aggressive forms of breast cancer and their relatives.”

The study identified 511 African American women with breast cancer from The University of Chicago Cancer Risk and Breast Cancer clinics from 1992 to 2011. Women who were related or had only limited DNA available were excluded, and 249 probands were analyzed for the presence of mutations in 18 breast cancer susceptibility genes using the BROCA assay.

Of the 249 subjects, 56 (22%) carried at least one loss-of-function mutation, distributed among BRCA1 (n=26), BRCA2 (n=20), ATM (n=5), CHEK2 (n=3), PALB2 (n=3), and PTEN (n=1). Of the 79% who had BRCA1 or BRCA2 alone, 4% (two of 46) had large rearrangements. Three women had more than one mutation, two of whom had no family history of breast cancer; one was estrogen receptor (ER)–positive/progesterone receptor (PR)–positive and one had triple-negative breast cancer (TNBC).

“The majority of mutations were unique,” Dr. Churpek reported. “Damaging mutations were carried by 30% of patients with TNBC, 27% of patients diagnosed at age 45 years or older, 49% with a second breast primary, and 30% with a family history of either breast or ovarian cancer in any close relative.”

Andrew D. Seidman, MD, ASCO spokesperson and breast cancer expert, said “These results argue for increased screening for mutations in African-American women diagnosed with breast cancer at a younger age, with TNBC, and/or with a family history. Since such testing may lead to life-saving interventions for their family members, these data underscore the need to overcome barriers to genetic testing for breast cancer risk among African-American women.”

This research was supported in part by the National Institutes of Health, the Breast Cancer Research Foundation, and Komen for the Cure.