NEW YORK – Breast cancer patients with a greater proportion of Indigenous American genetic ancestry appear more prone to having tumors of the HER2-positive subtype, according to new research from the University of California, San Francisco and elsewhere, though additional work is needed to tease out potential genetic contributors to this propensity.
"The association between IA ancestry and HER2 status suggests that population-specific variants of IA origin could be partly contributing to the higher incidence of HER2-positive breast cancer in Latinas," senior author Laura Fejerman, an associate professor of medicine at UCSF, said in a statement, noting that "[o]ur ongoing research aims to identify the specific germline variants that may lead to this association."
Using array-based genotyping profiles and other data collected from 1,300 individuals from Lima, Peru for the Peruvian Genetics and Genomics of Breast Cancer (PEGEN-BC) study, the researchers found that increasing levels of Indigenous American ancestry coincided with enhanced HER2-positive breast cancer incidence. They further validated the association using data for another 616 breast cancer patients from Mexico and Colombia.
The team noted that the findings, published in the journal Cancer Research on Friday, could inform some breast cancer cases involving Latin American women in other parts of the world, including the US.
"This study highlights the importance of studying diverse populations and collaborating with other countries," Fejerman said. "We need to understand diverse populations so that we may someday be able to provide precision cancer prevention and care to everyone, and not just a subset of the population."
Past studies suggested that women with Latin American ancestry tend to have lower rates of breast cancer overall, the authors explained. But when they are diagnosed with the disease, it is often at a more advanced stage and has more deadly outcomes than cases diagnosed in their Caucasian counterparts.
For the latest analysis, Fejerman and colleagues from the US, Peru, and Mexico first brought together array-based genotyping profiles for 1,312 PEGEN-BC participants diagnosed with invasive breast cancer over the past decade at Lima's Instituto Nacional de Enfermedades Neoplásicas. On average, the participants had 76 percent Indigenous American ancestry, they reported, along with 18 percent European, 4 percent African, and 2 percent East Asian ancestry.
Some 30 percent of these patients had HER2-positive tumors, with or without estrogen receptor or progesterone receptor positivity, the team reported, and the likelihood that an individual's breast cancer fell into the HER2-positive subtype incrementally notched up by an estimated 1.2-fold or more as Indigenous ancestry rose by 10 percent — findings supported by additional genetic and clinical data from 616 individuals with breast cancer from Mexico and Colombia.
Conversely, the researchers saw a relative dip in the prevalence of tumors with pronounced expression of HER2, but not of the estrogen or progesterone receptors, as the proportion of European ancestry escalated.
From these and other findings, the authors concluded that the "positive association between Indigenous American genetic ancestry and [HER2-positive] breast cancer suggests that the high incidence of [HER2-positive] subtypes in Latinas might be due to population and subtype-specific genetic risk variants."