Researchers have published the first known detailed study of breast cancer tissue from Native American women.

The study, published in npj Precision Oncology, 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 higher mortality rates.

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 Jun Li, a corresponding author of the study and professor in the Department of Applied and Computational Mathematics and Statistics at Notre Dame.

“Our study is the first to look closely at the biology of breast tumours in Native American women, and it's overdue.”

Researchers compared the genetic makeup of 17 Native American breast cancer tumour tissues to nearly 700 breast cancer tissues from white women from The Cancer Genome Atlas.

Breast cancer tissue from Native American women in the study showed differences in which genes carried mutations, how the tumours used their DNA and which genes were turned on or off.Many of those differences pointed to the immune system. 

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

“We found differences at every level we looked at. Several genes were mutated much more often in tumours from Native American women than white women, including some that are critical for the immune system to recognise 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 Harper Cancer Research Institute that aims to collect tumour 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 Sharon Stack, 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 grey hair, blue eyes, wearing a textured green blazer, gold hoops, and silver chain.

The programme 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 repository 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.

Laurie Littlepage, 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 Defence Breast Cancer Research Programme Breakthrough Award.

Article: Molecular profiling of breast cancer in native American women reveals distinct genomic and transcriptomic features

Source: University of Notre Dame