New Nature Cancer study identifies molecular differences between primary breast cancer and metastatic breast cancer

A multi-agency national study has identified unique molecular characteristics
that contribute to the development and progression of metastatic breast cancer.
One of the key features involves changes in the immune system, which are partly due to methylated antigen genes; Methylation is the addition of a small chemical group
to the DNA molecule.
Local deletion, or partial loss of antigen genes, has also been found and mutually exclusive samples with DNA methylation
.
In this study, methylation and focal deletion resulted in fewer immune cells available to attack cancer cells
.

The findings were published December 30, 2022 in
Nature Cancer.

This study, led by the AURORA US Transfer Network Program, was one of the first studies to use multiple genomic platforms to analyze primary (primitive) tumors and their paired metastases; Most early studies looked at primary or metastatic cancer
in isolation.
In the new study, which involved 55 women with metastatic breast cancer, researchers collected tumor tissue
representing 51 primary cancers and 102 paired metastatic breast cancers.

"This study involves a broad collaboration of many institutions to advance our understanding of breast cancer, and what we know about breast cancer biology comes from studying primary tumors, but when people die of breast cancer, it is due to metastatic disease, so our lack of understanding of metastatic biology hinders patient care
.
"

The scientists found that T cells and B cells, which primarily direct the anti-tumor immune response, were significantly less
involved in metastasis.
The researchers also looked at differences between different metastatic sites; Liver and brain metastases have lower levels of immune cell response compared to lung metastases
.

"We found that about 17 percent of metastatic tumors have a reduced expression of genes that affect cellular immunity, and immune cells have a reduced ability to penetrate the environment and fight cancer cells.
"

"THIS FINDING REPRESENTS ONLY THE FIRST HALF OF THE AURORA U.
S.
TRANSFER NETWORK PROJECT, AS RESEARCHERS RECENTLY LAUNCHED A CLINICAL TRIAL TO HELP COLLECT MORE SAMPLES, AND THE RESULTS OF THE ANALYSIS OF THE TRIAL SAMPLES WILL BE ADDED TO THE CURRENT DATA, ENABLING BETTER DETECTION OF GENOMIC CHANGES THAT CAN REALLY ENHANCE OUR UNDERSTANDING
OF THE DISEASE.
"

"We saw biological changes in about 30 percent of patients, including loss of immune activation, particularly in liver and brain metastases, many of which occur
through mechanisms that can be reversed or treated.
So, based on this effort, we are very excited about
the potential to improve the treatment of metastatic disease, or even prevent metastasis itself.
”

Larry Norton, MD, founding scientific director of the Breast Cancer Research Foundation, said: "This vital study—which identifies a potential new target for controlling metastatic disease—demonstrates the value of
broad, collaborative research united by people dedicated to important missions.
"

"We are very grateful to our patients for helping us advance these research efforts and for any contributions they may make in the future
," Perou said.
"We are currently mimicking a large number of these genetic findings in our mouse models, and we are testing new treatments with real progress that we hope will pay off
for patients in the near future.
"