Attendees and poster presenters during Posters Sessions
Attendees and poster presenters during Posters Sessions at the American Society of Clinical Oncology (ASCO) | Courtesy: ? ASCO/David Eulitt 2017.

Researchers from Ambry Genetics, a clinical genetics testing company which is part of Konica Minolta Precision Medicine, and Mayo Clinic, have documented significant differences in the prevalence of hereditary genetic mutations, also called germline mutations*, linked to breast cancer among racial and ethnic populations compared to non-Hispanic White women.

Results from a collaborative study will be presented during the annual meeting of American Society of Clinical Oncology (ASCO), held May 31 to June 4, 2019 in Chicago, Ill.


?The prevalence of germline mutations and associated germline genetic drivers of breast cancer risk in racial and ethnic populations is largely unknown, and much of the known risk that is cited in the literature has been studied in non-Hispanic White populations,? noted Siddhartha Yadav, MD, a Hematology and Oncology Fellow at the Mayo Clinic working in the lab of Fergus Couch, PhD, Zbigniew and Anna M. Scheller Professor of Medical Research Chair, Division of Experimental Pathology and Laboratory Medicine Mayo Clinic.

Blind Spot

?That?s a clinical ?blind spot? that needs to be addressed because a better understanding of racial or ethnicity-specific genetic risk for breast cancer is key to improved targeting of genetic testing and more informed management of patients in these populations,? Yadav added.

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In a study conducted by Mayo Clinical and Ambry Genetics between March 2012 through December 2016, a population of 77,900 women with breast cancer, comprised of 57,003 non-Hispanic White, 6,722 Black, 4,183 Asian, 5,194 Hispanic and 4,798 Ashkenazi-Jewish subjects, underwent germline multigene panel testing of cancer genes. The prevalence of gene mutations in racial and ethnic populations relative to non-Hispanic Whites was assessed.

Results revealed numerous differences between populations that may have important clinical implications.

Among them are the frequency of pathogenic mutations in known breast cancer genes was 7.5% for Asians and Ashkenazi-Jews and 8.7% for non-Hispanic Whites, compared to 9.7% for Blacks and 9.9% for Hispanics.

Distribution of variants of uncertain significance (VUS), a variant classification indicating unknown relevance to disease, also differed, being most frequent among Asians (29%), followed by Blacks (27%), Hispanics (21%), non-Hispanic Whites (16%) and Ashkenazi-Jews (14%).

However, the researchers note that among genes with mutation counts large enough for assessment, mutations in BARD1, BRCA1, BRCA2, PALB2 and TP53 were significantly associated with clinically relevant increased risks (odds ratio (OR) > 2) of breast cancer across all ethnicities and races.

The findings contribute to a better understanding of breast cancer risk.

?As we pursue further research in this area, the now documented differences in the prevalence of mutations in breast cancer genes among major racial and ethnic population in the U.S. underscores two issues. First, the importance of considering all ethnicities when developing guidelines and best practices for genetic testing, screening and management of patients predisposed to breast cancer, and second, a need for larger study cohorts in ethnic minority populations,? explained Brigette Tippin Davis, Ph.D., FACMG, senior vice president of research and development of Ambry Genetics.


*Germline mutations refer to a gene change in a body’s reproductive cell that becomes incorporated into the DNA of every cell in the body of the offspring. Germline mutations are passed on from parents to their offspring and also called hereditary mutation.


[1] Yadav S, LaDuca H, Polley E, Shimelis H, Niguidula N, Hu C, Lilyquist J, et al. Racial and ethnic differences in the results of multigene panel testing of inherited cancer predisposition genes in breast cancer patients. J Clin Oncol 37, 2019 (suppl; abstr 1514) | Poster Session: Monday June 3, 1:15 PM to 4:15 PM, Location: Hall A (Board #8) | Poster Discussion Session: Monday June 3, 4:30 PM to 6:00 PM, Location: S103 [Abstract]

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