Breast tumors can shift their appearance as the cancer becomes more aggressive.
Researchers led by Darren Patten, from the Department of Surgery and Cancer at Imperial College London (ICL) in the United Kingdom, set out to study the role of a molecule called Yin Yang in the advancement of breast cancer tumors.
Yin Yang is a transcription factor — that is, a type of protein that helps DNA transform, or transcribe, into RNA.
All cells in a healthy body need this transcription factor because only a specific number of genes that form a cell need to be activated at a given time for the cell to function properly.
However, in the case of cancer, researchers were unsure of the role that this transcription factor had in tumor growth.
To find out, Patten and colleagues conducted genetic profiling of tumors from 47 patients with breast cancer. Their findings were published in the journal Nature Medicine.
Luca Magnani, also from the Department of Surgery and Cancer at ICL, is the corresponding author of the study.
Analyzing the epigenetic profile of tumors
Patten and team used a variety of gene profiling and gene editing methods, including CRISPR — a revolutionary genetic engineering technique — to study estrogen-receptor-positive breast cancer.
In this type of cancer, which accounts for approximately 80 percent of all breast cancer cases, tumors have receptors of the female sex hormone estrogen.
In total, the researchers examined 34 tumors from people whose cancer had not metastasized, and 13 tumors from people whose breast tumors had spread throughout the rest of the body.
More specifically, the researchers analyzed the epigenetic profile of the tumors — that is, they looked at which genes were active and which genes were inactive in the tumors. By switching the right genes on and off, cancer tumors are able to change their “appearance” so that chemotherapy drugs don’t target them.
The scientists tracked the behavior of so-called enhancers, or chemical alterations in the DNA that instruct cells to activate and deactivate selected genes.
Patten and colleagues found that two enhancers in particular, which serve to regulate the genes SLC9A3R1 and Yin Yang 1, are switched on at certain key points in the tumor growth process.
These genes are activated, the researchers show in their paper, as the tumors become more aggressive.
The study also revealed that cancer cells rely much more on Yin Yang for their growth than normal cells. So, the researchers believe that Yin Yang 1 in particular fuels tumor growth.
‘We advise always taking a second biopsy’
The findings, Magnani says, should change current therapeutic practices. “At the moment, patients usually have a biopsy when they are first diagnosed with breast cancer. Doctors then analyze this tissue sample to identify what type of breast cancer a patient has, as this will dictate the best treatment for them.”
“However,” he adds, “our results suggest tumors switch different genes on and off as they progress, and can fundamentally change their ‘appearance.'”
“Therefore if a tumor becomes more aggressive, and spreads around the body, we would advise always taking a second biopsy. The cancer might have changed significantly in this time, and would respond to different treatments.”
The corresponding author continues, saying, “Although taking a second biopsy when a patient’s cancer relapses is becoming much more common, it’s still not happening all the time.”
Magnani also adds that the findings have raised a lot of questions, which the team now needs to answer.
To do so, the scientists aim to replicate their results in a much larger number of tumor samples, and to study the behavior of Yin Yang in triple-negative forms of breast cancer.