Better Gauging Breast Cancer Risk in Women Veterans of African Ancestry

PORTLAND, OR – Polygenic risk scoring (PRS) appeared to work well in predicting incident breast cancer for a prospective cohort of European (EUR) ancestry women veterans but not as well for those of African ancestry, according to a recent study.

“This is not surprising as most genome-wide association studies were conducted in people of European ancestry,” wrote the researchers from the VA Portland Health Care System and the Oregon Health & Science University. “This is an important area of health disparity and unmet need. “

The answer to the dilemma might be found in the large population size and diversity of the VA’s Million Veteran Program (MVP). The study in the journal Health Equity noted that the MVP provides “a unique and important opportunity to explore novel approaches to produce accurate and clinically useful genetic risk prediction instruments for minority populations.”1

Background information in the article advised that breast cancer is a leading cause of cancer death for American women and a very serious issue for women veterans. A recent MVP analysis found that out of 53.5 thousand women veterans from the MVP without prior breast cancer diagnosis (mean age at entry 48.8 and 30.0% of African [AFR] ancestry), 818 new breast cancer diagnoses occurred over a median follow-up of 5.7 years. That equates to a breast cancer incidence of 2.70 per 1000 per year.

While breast cancer screening with mammography leads to a reduction in mortality from breast cancer, the authors noted, they decried the current “one size fits all,” breast cancer screening strategy for all but very high-risk women, such as those with BRCA mutations or prior chest wall irradiation.

“Appropriate risk assessment is highly desirable as higher risk women may benefit from more intense screening approaches, whereas lower risk women may do equally well with less intensity, therefore, avoiding the cost and inconvenience of screening,” the study pointed out.

The report also discussed how tamoxifen has been approved for women above the age of 35 years for breast cancer prevention if they have an elevated risk, as seen with an average 65-year-old Caucasian woman.

An increasing number of characteristics are being used to predict a woman’s risk of developing breast cancer, according to the study including:

  • age;
  • mutation status for breast cancer genes, such as BRCA1and BRCA2;
  • family history of cancer;
  • personal history of benign breast biopsy;
  • history of benign breast disease, such as atypia;
  • exposure to hormones;
  • breast density as seen on mammography; and more recently,
  • background parenchymal enhancement on MRI.

“Harnessing these features may enable us to more precisely assess the risk of breast cancer development,” the researchers wrote. “Understanding individuals’ risks for developing breast cancer may allow us to adopt a more appropriate breast cancer screening and/or prevention strategy. Recent successes from genome-wide association studies (GWAS) of breast cancer (e.g., A study with more than 150,000 breast cancer cases and more than 110,000 controls5) have led to a growing literature on the development and evaluation of breast cancer risk prediction models…”

The authors said they found that PRS313 screening underperformed in a prospective cohort of women veterans of AFR ancestry in the MVP, which was consistent with prior cross-section orcase–control studies.

“This is a significant area of unmet need, as African Americans have higher risk of developing early-onset breast cancer and about 40% higher breast cancer mortality than other ancestral groups in the United States,” the study team wrote.

It added,  “As a result of sample size and possibly different genetic architecture between the two populations, only six loci were identified from individuals of African ancestry, even after trans-ethnic analysis, in comparison with more than 200 loci reported from individuals of European ancestry. The differential performance of PRS across ancestral groups raises a significant concern about potentials to exacerbate health disparities and evokes ethical controversy surrounding the clinical implementation of PRS in general. It is, therefore, essential to include participants representing diverse populations in genomic medicine studies to ensure equitable benefit from scientific discoveries and to prevent further increase in health disparities.”

The researchers said they performed a combined analysis with additional cases and controls from the MVP to increase the gain in statistical power for novel locus discoveries in different ancestral groups. “Although the most straightforward solution to increase PRS performance across ancestral groups is to build well-powered GWAS resources for diverse populations,” they maintained, “we will entertain an alternative approach by taking advantage of the observation that genetic data from different ancestral groups still share substantial information, although with differences in allele frequency, linkage disequilibrium structure, and genetic architecture.”

Another effort involves borrowing information from European ancestral groups to help boost the power of predictions in non-European ancestral groups.

  1. Luoh SW, Minnier J, Zhao H, Gao L. Predicting Breast Cancer Risk for Women Veterans of African Ancestry in the Million Veteran Program. Health Equity. 2023 May 26;7(1):303-306. doi: 10.1089/heq.2023.0011. PMID: 37284538; PMCID: PMC10240329.

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