Jun Li stood before a stark reality: the world's largest breast cancer database, The Cancer Genome Atlas, contains more than a thousand patient records—and only one of them is Native American. That gap has meant therapies and tests are built from the genetic signatures of other populations, then assumed to work equally well for everyone. Now, researchers at the University of Notre Dame have published the first detailed genetic study of breast cancer in Native American women, and what they found suggests that assumption may be dangerously incomplete.
The disparity in breast cancer is a puzzle wrapped in urgency. Native American women have lower incidence rates than white women, yet they face higher mortality rates—and unlike the broader population, those death rates have remained stubbornly stagnant even as outcomes have improved elsewhere. To understand why, Sharon Stack's team at Notre Dame's Harper Cancer Research Institute analyzed tumor tissue from 17 Native American women and compared it to nearly 700 samples from white women in the Cancer Genome Atlas. What emerged across every level of analysis were consistent genetic differences that could reshape how oncologists approach treatment.
The tumors from Native American women carried mutations in different genes than those from white women, used their DNA in distinct ways, and expressed different patterns of which genes were turned on or off. Many of these differences pointed directly to the immune system—the body's first line of defense against cancer. "Tumors from Native American women appeared to hide from the body's immune defenses in fundamentally distinct ways," Li explained. Several genes critical for immune system recognition of cancer cells showed higher mutation rates in Native American tumors. Most striking, a few immune-related genes were mutated exclusively in Native American patients, found nowhere in the white patient cohort.
These molecular differences hold real clinical implications. How tumors evade immunity directly affects whether immunotherapies will work, and differences in genes protecting against DNA damage could influence chemotherapy responses. Yet Li is careful about the limits of what the study shows. "This research is meant to generate hypotheses, not change treatment guidelines," he said. The genetic story is only part of a much larger picture—socioeconomic factors, environmental exposures, healthcare access, and other social determinants of health all likely play crucial roles in the mortality disparity.
What makes this research significant is not just what it found, but what it signals about the future. This is the opening move in a broader research initiative at Harper Cancer Research Institute aimed at collecting tumor tissues from populations systematically underrepresented in cancer research. The team plans to continue building partnerships with Native American communities, focusing on cancers most prevalent for them, while also beginning to collect samples from other underrepresented groups—Panamanian and Kenyan women among them. Those tissues will feed into Harper's biosample repository and tissue banking service, becoming a resource for researchers and clinicians across the region and beyond.
For Stack, the work embodies the university's commitment to being "a powerful means for doing good by working with underserved communities with worse cancer outcomes." Science cannot fix what it does not see. By making Native American breast cancer biology visible—by treating it as a distinct research question rather than an afterthought—Notre Dame is beginning to correct a gap that has persisted for far too long.