Researcher: Triple negative breast cancer hijacks immune system

For years, researcher Mikala Egeblad has been on the hunt for the mechanisms that explain why breast cancer — a curable condition — sometimes becomes aggressive, difficult to treat, or even deadly.

Two years ago, the Cold Spring Harbor Laboratory associate professor explained why certain forms of the disease are more likely to resist lifesaving treatments. Those ongoing studies are at the core of her overall mission: shedding light on the molecular underpinnings of difficult forms of the disease.

Now, Egeblad has discovered how the immune system, normally a powerful ally in keeping invasive diseases at bay, plays a subversive role in a form of the malignancy called triple negative breast cancer.

“Scientists all over have been trying to take apart each step that cancer cells use to spread to a tissue. This step was not known,” Egeblad said of her discovery, which reveals how this form of breast cancer exploits cells in the immune system to spread. In 2014, Egeblad was one of only two scientists in the nation to win a coveted $2.5 million award from the Department of Defense, which is funding innovative research aimed at curing breast cancer.

Triple negative breast cancer accounts for 10 percent to 20 percent of all cases of the disease in this country, according to the National Breast Cancer Foundation. It can be tough to treat, foundation experts say, because by its very definition — triple negative — this form of breast cancer is missing all three receptors targeted by a range of highly successful medications.

Those receptors — progesterone, estrogen and HER-2/neu — are identifying proteins studding the surface of cancer cells, serving as their signatures. Drugs have been developed to home in on each protein to disrupt signals driving these forms of breast cancer.

But for those with triple negative breast cancer, doctors often have to try different combinations of medications to control the disease. Sometimes they are confronted with substantial challenges, particularly when the disease spreads — and that is where Egeblad’s discovery is shedding new light.

She has found that neutrophils, the most abundant cells in the immune system, are hijacked in a seemingly sinister plot by triple negative cancer cells. Neutrophils possess an extraordinary feature: They are capable of casting dense weblike “nets” of DNA. The structures are stippled with toxic enzymes aimed at destroying and digesting invaders and ejected to ensnare invaders, such as bacteria and yeasts.

These structures, aptly named neutrophil extracellular traps, or NETs, Egeblad said, are exploited in triple negative cancer to bolster the malignancy’s capacity to spread.

She has found how an immune system cell becomes an unwitting turncoat, assisting the cancer cell in metastasis. And it is metastasis — spreading to distant sites in the body — that makes any cancer deadly, Egeblad said.

“Our experiments showed that the NETs, in such situations, can promote metastasis,” Egeblad said.

Remarkably, she has seen this activity in real time via live imaging, which has allowed her to fully document the ability of cancer cells to induce neutrophils to eject their NETs even when no infection or invader was present.

“Not all triple negative breast cancer metastasizes,” Egeblad said. But she is certain that webs of DNA are being released — and hijacked — by cancer cells, a discovery that adds a giant piece to the puzzle about a mystifying form of breast cancer.

Triple negative can affect anyone, though it is more prevalent in women under 50, African-Americans, Hispanics, and those with a BRCA1 gene mutation, according to the Triple Negative Breast Cancer Foundation, which also reports that this subtype is more likely to spread and recur.

To help the public understand her ongoing studies, Egeblad periodically presents her research to breast cancer support groups. Her aim is ensure that virtually anyone can understand the work underway in her laboratory — and how it advances overall scientific knowledge about the disease.

Egeblad recently presented her work on NETS to the West Islip Breast Cancer Coalition.

“One thing that’s been really good for me is meeting with breast cancer survivors to discuss the big picture,” she said.

Support group members in West Islip had no problem understanding this form of breast cancer or a summary of Egeblad’s investigations.

“Triple negative breast cancer is very complex,” said Joanne Marquardt, a breast cancer survivor and research advocate for the coalition.

Marquardt, a retired earth sciences teacher in the Massapequa school district, said Egeblad’s explanation about NETS and how cancer cells exploit them was not only clear, but enlightening.

“This form of breast cancer is really very insidious and its goals are to survive and spread,” Marquardt said.

Egeblad said the next step in her research is to examine a larger population of cells to determine whether the weblike structures are being subverted in earlier phases of the disease.