Understanding the Microbial Structure of Triple Negative Breast Cancer

Study may lead to enhanced efficacy of breast cancer drugs.

Scientists have long known that cancer comes as the result of normal cellular functions going wrong on a genetic level.

However, increasing evidence points to the human microbiome as the key player in either setting the stage for cancer or even directly causing some forms of it.

A study from the Perelman School of Medicine at the University of Pennsylvania has identified for the first time an association between 2 microbial signatures and triple negative breast cancer (TNBC), the most aggressive form of the disease.

“Viruses and other microorganisms probably have much more to do with cancer, at least the propagation of cancer and promotion of it, than is really known,” said James C. Alwine, PhD, a professor of Cancer Biology and associate director for core services at the Abramson Cancer Center.

The group of scientists used a microarray technology called PathoChip, which contains 60,000 molecular probes to identify all known viruses and pathogenic bacteria, fungi, parasites, and other microorganisms, to screen tissue samples from 100 TNBC patients.

In addition, researchers examined 40 matched and non-matched controls. Matched controls are non-tumor tissue from TNBC patients and non-matched controls are breast tissue from health patients.

The researchers discovered a distinct microbial signature that distinguished TNBC tissue from normal samples, which could be broken down into 2 groups: 1 predominantly viral and the other predominantly bacterial, with some fungi and parasites.

“If we look at this closely, we may also find some smaller clusters within those major groups that could give us some insights to unique identifiers for individuals in these clusters,” said Erle S. Robertson, PhD, a professor of Microbiology and associate director for global cancer research and co-leader of the tumor virology program at the Abramson Cancer Center. “The team found about 30 organisms that provide a specific type of signature to give us clues for developing a diagnostic tool.”

Herpesviruses, Parapoxviruses, Retroviruses, Hepadnaviruses, Polyomaviruses, and Papillomaviruses were among the most likely to be detected in the study. Bacterial signatures included Arcanobacterium, Brevundimonas, Sphingobacteria, and Geobacillus.

Fungal and parasitic organisms included Pleistophora and Piedra, and Foncecaea and Trichuris, respectively.

While the detection of these and other pathogens in TNBC tissues does provide some insight for scientists, Alwine and researchers emphasize that this does not necessarily mean that they actually cause cancer.

“There are a lot of different ways to look at this,” he said. “It’s possible that some of the organisms we’re looking at have a causative effect, but we don’t know that. We can’t say until it’s been thoroughly tested by many more experiments.”

One possibility is that the organisms could be adding something to the cellular microenvironment that helps damaged cells to become malignant or pushes them over the edge into cancer.

A separate possibility is that certain organisms may simply find tumor tissue to be a more comfortable environment, without necessarily being involved in the processes of cancer.

“They might just be there because it’s a good place to hang out,” Alwine said.

Either possibility yields important information to scientists about how to better develop diagnostic tools.

“We’re looking at different cancers to find out whether or not there are specific signatures that go with specific cancers,” Robertson said. “We are also trying to come up with ways in which we can look at blood samples to see if we can potentially develop a test to detect these signatures, which might provide an early surveillance system for identifying patients who might be prone to developing these malignancies. The microbial signatures may also have therapeutic implications.”

“Many of these microorganisms can metabolize drugs and so their presence might diminish the effect of some drugs and might guide the ability to decide what to use for treatment of cancer,” Alwine said.

In collaboration with the breast oncology group at Penn Medicine, the research team plans to further explore these possibilities.

“We’re not trying to say that any of these organisms are directly causing cancer,” Alwine said. “We’re trying to identify the specific cancer signature, so that we can figure out ways to treat, control, or modify the cancer or treat the tumor-associate microbes, to prevent these malignancies in the first place. We’ve now opened up the doors to look more specifically at what these organisms are actually doing.”