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Are There Differences in the Prevalence of Germline Pathogenic Variants in Susceptibility Genes in Black vs White Women With Breast Cancer?


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In a population-based study reported in JAMA Oncology, Susan M. Domchek, MD, and colleagues found “no clinically meaningful differences” in the prevalence of germline pathogenic variants in 12 established breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer in the United States.

Susan M. Domchek, MD

Susan M. Domchek, MD

Study Details

The study used data from patients with breast cancer included in the population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium from June 1993 to June 2020. Patients were unselected for family history or age at breast cancer diagnosis. Prevalence of germline pathogenic variants in ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, and TP53 were determined.

Key Findings

A total of 3,946 Black women (mean age at diagnosis = 56.5 years) and 25,287 White women (mean age at diagnosis = 62.7 years) with breast cancer were included in the analysis.

Compared with White women, Black women were more likely to be diagnosed at a younger age and with estrogen receptor–negative disease and triple-negative disease, less likely to have a first-degree relative with breast cancer, and more likely to have a family history of ovarian cancer (all P < .001).

The combined prevalence of germline pathogenic variants in the 12 genes was 5.65% in Black vs 5.06% in White women (P = .12).

Among individual genes, White women were more likely to have pathogenic variants in CHEK2 (1.29% vs 0.38%, P < .001) and Black women were more likely to have pathogenic variants in BRCA2 (1.80% vs 1.24%, P = .005) and PALB2 (1.01% vs 0.40%, P < .001). No significant differences for other genes were observed.

KEY POINTS

  • The combined prevalence of germline pathogenic variants in the 12 genes was 5.65% in Black vs 5.06% in White women.
  • Among individual genes, White women were more likely to have pathogenic variants in CHEK2 and Black women were more likely to have pathogenic variants in BRCA2 and PALB2. No significant differences for other genes were observed.

Among 981 Black women vs 2,426 White women with estrogen receptor–negative disease, the overall prevalence of pathogenic variants among Black vs White women did not significantly differ (9.28% vs 8.08%, P = .28). Among individual genes, Black women were more likely to have pathogenic variants in PALB2 (1.83% vs 0.95%, P = .04).  

Among 1,155 Black women vs 3,415 White women diagnosed before age 50, there was no difference in overall prevalence of pathogenic variants (8.83% vs 10.04%, P = .25). Among individual genes, White women were more likely to have pathogenic variants in CHEK2 (1.82% vs 0.43%, P <.001).

In analysis adjusted for age at diagnosis, the standardized prevalence ratio of pathogenic variants in the 12 genes for White vs Black women was 1.08 (95% confidence interval = 1.02–1.14), with the difference in BRCA2 pathogenic variants no longer being statistically significant. Four previously nonsignificant genes—consisting of ATM, BRCA1, RAD51D, and TP53—became statistically significant; all but RAD51D appeared to have a higher prevalence of pathogenic variants in White vs Black patients.

The investigators concluded, “In this large population-based study of women with breast cancer, no clinically meaningful difference in the prevalence or distribution of pathogenic variants was seen in U.S. Black compared with non-Hispanic White cases. Although the prevalence of pathogenic variants in three genes—CHEK2, BRCA2, and PALB2—differed statistically between the two populations, the absolute differences were small….The findings suggest that there is not sufficient evidence to make policy changes related to genetic testing based on race alone. Instead, all efforts should be made to ensure equal access to and uptake of genetic testing to minimize disparities in care and outcomes.”

Dr. Domchek, of the Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the JAMA Oncology article.

Disclosure: The CARRIERS study was supported by grants from the National Institutes of Health and Breast Cancer Research Foundation. For full disclosures of the study authors, visit jamanetwork.com.

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®.
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