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Brief Report
May 27, 2021

Comparison of the Prevalence of Pathogenic Variants in Cancer Susceptibility Genes in Black Women and Non-Hispanic White Women With Breast Cancer in the United States

Author Affiliations
  • 1Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 2Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York
  • 3Keck School of Medicine, University of Southern California, Los Angeles
  • 4Mayo Clinic, Rochester, Minnesota
  • 5Huntsman Cancer Institute, University of Utah, Salt Lake City
  • 6Slone Epidemiology Center at Boston University, Boston, Massachusetts
JAMA Oncol. 2021;7(7):1045-1050. doi:10.1001/jamaoncol.2021.1492
Key Points

Question  Is there a difference in the prevalence of germline pathogenic variants in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer?

Findings  In this case-control study of 3946 Black and 25 287 non-Hispanic White women with breast cancer from population-based studies, there was no difference in prevalence of germline pathogenic variants.

Meaning  Changes to guidelines related to genetic testing for women with breast cancer should not be based on race alone.

Abstract

Importance  The prevalence of germline pathogenic variants (PVs) in cancer susceptibility genes in US Black women compared with non-Hispanic White women with breast cancer is poorly described.

Objective  To determine whether US Black and non-Hispanic White women with breast cancer have a different prevalence of PVs in 12 cancer susceptibility genes.

Design, Setting, and Participants  Multicenter, population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Participants were Black and non-Hispanic White women diagnosed with breast cancer, unselected for family history or age at diagnosis. Data were collected from June 1993 to June 2020; data analysis was performed between September 2020 and February 2021.

Main Outcomes and Measures  Prevalence of germline PVs in 12 established breast cancer susceptibility genes.

Results  Among 3946 Black women (mean [SD] age at diagnosis, 56.5 [12.02] y) and 25 287 non-Hispanic White women (mean [SD] age at diagnosis, 62.7 [11.14] y) with breast cancer, there was no statistically significant difference by race in the combined prevalence of PVs in the 12 breast cancer susceptibility genes evaluated (5.65% in Black vs 5.06% in non-Hispanic White women; P = .12). The prevalence of PVs in CHEK2 was higher in non-Hispanic White than Black patients (1.29% vs 0.38%; P < .001), whereas Black patients had a higher prevalence of PVs in BRCA2 (1.80% vs 1.24%; P = .005) and PALB2 (1.01% vs 0.40%; P < .001). For estrogen receptor–negative breast cancer, the prevalence of PVs was not different except for PALB2, which was higher in Black women. In women diagnosed before age 50 years, there was no difference in overall prevalence of PVs in Black vs non-Hispanic White women (8.83% vs 10.04%; P = .25), and among individual genes, only CHEK2 PV prevalence differed by race. After adjustment for age at diagnosis, the standardized prevalence ratio of PVs in non-Hispanic White relative to Black women was 1.08 (95% CI, 1.02-1.14), and there was no longer a statistically significant difference in BRCA2 PV prevalence.

Conclusions and Relevance  This large population-based case-control study revealed no clinically meaningful differences in the prevalence of PVs in 12 breast cancer susceptibility genes between Black and non-Hispanic White women with breast cancer. 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.

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    1 Comment for this article
    EXPAND ALL
    Importance of investigating differences in mutation prevalence between ethnic groups
    takuma hayashi, MBBS, DMSci, GMRC, PhD | National Hospital Organization Kyoto Medical Center
    Cancer research is progressing rapidly due to advances in genome analysis technology. As a result, cancer treatment tailored to the individual patient's medical condition is becoming possible, and new options for cancer treatment are being created.

    The large population-based case-control study conducted by Domchek SM. et al. revealed no clinically meaningful differences in the prevalence of pathogenic variants (PVs) in 12 breast cancer susceptibility genes (ATM, BARD1, BRCA1, BRCA2, CDH11, CHEK2, NF1, PALB2, PTEN, RAD51C, RAD51D, TP53) between Black and non-Hispanic White women with breast cancer.

    In Japan, cancer genomic medicine was started in insurance medical care from
    around December 2019. By December 2020, cancer genomic medicine was performed in about 576 cases at a national university hospital in Japan, and drugs were recommended for 29% (167/576) cases.

    Cancer genomic medicine conducted at a national university hospital in Japan revealed PVs in BRCA1/2, NF1, PTEN, TP53 and ERBB2 amplification, FGFR1 amplification, PD-L1 amplification in breast cancer patients.

    Based on the large-scale clinical study conducted by Domchek SM et al. and the results of cancer genomic medicine conducted at a national university in Japan, it was found that there is no clinically significant difference in the prevalence of pathogenic variants (PVs) of breast cancer susceptibility genes between black women, non-Hispanic white women and Japanese women with breast cancer.

    Textbook-wise, mutation prevalence varies among ethnic groups and may be influenced by founder mutations. Penetrance can be influenced by mutation-specific phenotypes and the potential modifying effects of the patient's own genetic and environmental background. Although estimates of both mutation prevalence and mutation penetrance rates are inconsistent and occasionally controversial, understanding them is crucial for providing accurate risk information to each patient.

    Clinicians who are interested in providing personalized cancer-risk counselling for patients should understand potential modifying factors that are particular to a patient's ethnicity, family history and environmental influences.

    Dr. Takuma Hayashi and Dr. Ikuo Konishi
    National Hospital Organization Kyoto Medical Center
    CONFLICT OF INTEREST: None Reported
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