Women With Indigenous American Ancestry Have Higher Odds of HER2-Positive Breast Cancer

Indigenous American (IA) ancestry has been linked to an increased incidence of HER2-positive breast cancer, according to the Peruvian Genetics and Genomics of Breast Cancer Study (PEGEN-BC) study published inCancer Research.¹

“The risk of breast cancer—related mortality varies between different populations, with Latina women having a greater risk of breast cancer-specific mortality than non-Hispanic white women,” said co-author Laura Fejerman, PhD, associate professor of medicine at the University of California San Francisco, in a statement. “Latina women tend to be diagnosed with more aggressive breast cancer subtypes, which may contribute to their greater risk of mortality, among other factors.”

The subgroups included in the study were patients with estrogen receptor (ER)—positive, progesterone receptor (PR)–positive, HER2-negative tumors (49%); ER/PR-positive, and HER2-positive tumors (18%); ER/PR-negative, HER2-positive tumors (12%); and ER/PR-negative, HER2-negative tumors (15%). In terms of ancestry, a large proportion of patients in the study were IA (76%), 18% of patients were of European descent, 4% were of African descent, and 2% were of East Asian descent. Patients were also from various regions in Latin American, including Amazonas (n = 81), coastal (n = 1090), mountains (n = 137), and undetermined region (n = 4).²

The difference in the proportion of IA genetic ancestry between tumor subtypes was statistically significant (P= .023), the univariate analysis showed. On average, 80% of patients with IA ancestry had ER/PR-negative, HER2-positive tumors, whereas 75% had had ER/PR-positive, HER2-negative tumors. The association between IA ancestry and HER2 was substantial, regardless of covariates. 

The more IA ancestry present in a patient, the more likely they were to have HER2-positive breast cancer. The odds were 1.19 for every 10% increase in IA ancestry (P= .002). For the probability of patients with IA ancestry having ER/PR-negative, HER2-positive breast cancer, the odds were higher at 1.22 per 10% increase in IA ancestry. The statistical significance of the association between HER2-positivity and IA ancestry held up in the multivariable model (odds ratio [OR], 1.30; 95% CI, 1.10-1.55; P= .002).

The investigators noted that European ancestry is often found in those with IA ancestry, and the odds of HER2-positivity in their tumors were lower in patients with a higher amount of European ancestry. The results were unchanged by country of origin, and there was no association between protective variant rs140068132-G and HER2-positive breast cancer in patients with IA ancestry, according to logistic regression analysis.

Investigators replicated the analysis to determine the association between IA ancestry and HER2-positive tumors in patients from Mexico and Columbia. Similar to what was observed in the study population overall, the analysis showed a strong association between IA ancestry and HER2-positivity. Specifically, there was a 28% increase in probability of having HER2-positive tumors for every 10% increase in IA ancestry.

The PEGEN-BC included 1380 samples from 1312 participants for whom genome-wide wildtype data were available. The study was limited by the fact that no health controls were included, lack of epidemiological data, and lack of information related to environmental factors, lifestyles, and behavioral information.¹

The study was conducted because previous studies showed the same trends, with no clear reason as to why this disparity existed. It was also previously reported that IA ancestry was associated with a lower incidence of breast cancer, but the data were not clear about the various subtypes of breast cancer.²

“Our results provide support for the hypothesis that there might be population-specific genetic risk factors predisposing women of IA ancestry to develop HER2. tumors. Further studies are needed to confirm the genetic basis of this association and discover specific regions or variants within the IA genome. Ultimately, a better understanding of these and other etiologic factors explaining breast cancer HER2 status will result in better subtype-specific polygenic risk

prediction and improved targeted treatments, not only for women of Latin American origin but in all women,” wrote Marker et al in the study.

References

1. Indigenous American ancestry may be associated with her2-positive breast cancer [news release]. Philadelphia, PA: American Association for Cancer Research: April 3, 2020. https://bit.ly/3aP3qPu. Accessed April 7, 2020.
2. Marker KM, Zavala VA, Vidaurre T, et al. Human epidermal growth factor receptor 2