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First comprehensive look at breast cancer in Native American women reveals key genetic differences

Author: Brandi Wampler

ND Experts

M. Sharon Stack

M. Sharon Stack

Chemistry and Biochemistry

Invasive lobular mammary carcinoma immuno-stained for NOTCH4.  The NOTCH4 gene was one of 11 genes that were more frequently mutated in breast cancers from Native American women. Image shows nuclear localization of NOTCH4 (brown stain), indicative of active Notch signaling.  The Notch signaling pathway is associated with maintenance of cancer stem cells that can lead to therapy resistance and disease recurrence.
Image shows nuclear localization of NOTCH4 (brown stain), indicative of active Notch signaling. The Notch signaling pathway is associated with maintenance of cancer stem cells that can lead to therapy resistance and disease recurrence. (Image by Jeff Johnson from the Stack laboratory at Notre Dame.)

Researchers from the University of Notre Dame have published the first known detailed study of breast cancer tissue from Native American women. The study, , reveals important molecular differences that may impact the efficacy of therapies for female, Native American breast cancer patients.

Breast cancer rates in Native American women are low compared to white women, yet Native American women have . Although the overall breast cancer death rate has declined, it has remained stagnant for Native American women.

“The largest breast cancer database in the world, The Cancer Genome Atlas, contains more than a thousand breast cancer patients — and only one of them is Native American. That means today’s treatments and tests have effectively been built using data from other populations, and then assumed to work equally well for everyone,” said , a corresponding author of the study and professor in the at Notre Dame. “Our study is the first to look closely at the biology of breast tumors in Native American women, and it's overdue.”

Researchers compared the genetic makeup of 17 Native American breast cancer tumor tissues to nearly 700 breast cancer tissues from white women from . Breast cancer tissue from Native American women in the study showed differences in which genes carried mutations, how the tumors used their DNA and which genes were turned on or off.

Many of those differences pointed to the immune system. Li said that tumors from Native American women compared to those from white women appeared to “hide” from the body’s immune defenses in fundamentally distinct ways. Researchers also found differences in the genes that protect against DNA damage.

Smiling Asian man with short dark hair and glasses, wearing a black collared shirt with a light blue logo.
Professor Jun Li (Photo by Matt Cashore/University of Notre Dame)

“We found differences at every level we looked at. Several genes were mutated much more often in tumors from Native American women than white women, including some that are critical for the immune system to recognize cancer cells. A few of these immune-related genes were mutated only in Native American patients,” Li said.

Overall, these differences may affect how patients respond to immunotherapies and chemotherapies. However, Li explains the study is meant “to generate hypotheses, not change treatment guidelines.” More research is needed to determine the multiple factors that may impact Native American mortality rates including genetic, environmental, socioeconomic or other determinants.

This is the first study part of a new research focus from Notre Dame’s that aims to collect tumor tissues from populations typically underrepresented in cancer research. The goal is to help fill gaps in the understanding of cancer biology.

“This research focus goes really hand in hand with the University’s mission to be a powerful means for doing good by working with underserved communities with worse cancer outcomes,” said , the Kleiderer-Pezold Professor of Biochemistry at Notre Dame, the Ann F. Dunne & Elizabeth Riley Director of the Harper Cancer Research Institute and a corresponding author of the study. “While there may be many social determinants of health at play, at Harper we want to investigate if there are differences on the molecular level that impact cancer incidence and outcomes.”

Smiling white woman with shoulder-length gray hair, blue eyes, wearing a textured green blazer, gold hoops, and silver chain.
Sharon Stack, Kleiderer-Pezold Professor of Biochemistry at Notre Dame (Photo by Barbara Johnston/University of Notre Dame)

The program will also continue collecting cancer tissues from partnering Native American communities, focusing on the cancer types that may be most prevalent for them, as well as collecting breast cancer tissues from other underrepresented populations such as Panamanian and Kenyan women.

The tissues will be sent to the Harper’s biosample and processed through their tissue banking service, which serves as a resource for researchers and doctors in South Bend and beyond.

“When you study a population that has been left out, you often discover biology that nobody knew was there,” said Li, also affiliated with the Harper Cancer Research Institute. “Those discoveries sharpen our understanding of cancer and ultimately, improve care for everyone.”

The lead author of the study was Fangfang Guo, a graduate student in Jun Li’s lab. , the Campbell Family Associate Professor of Cancer Research at Notre Dame, also co-authored the study.

The study was funded by the Ryan Gee Excellence Fund for Cancer Research with additional support from the National Cancer Institute and Department of Defense Breast Cancer Research Program Breakthrough Award.

Contact: Brandi Wampler, associate director of media relations, 574-631-2632, brandiwampler@nd.edu