New approaches target aggressive breast cancers

As National Breast Cancer Awareness Month draws to a close, pink ribbons and pink products slowly disappear from stores and businesses. But the disease remains at the forefront for patients who live with cancer and researchers working to eliminate it. Here we share some of the ways scientists at ASU are working to improve prevention, diagnosis and treatment of breast cancer.

MaryEllen Sheppard remembers going to her annual physical and hearing the doctor call her the “poster woman of health.”

“I didn’t feel sick. I was healthy, had high energy and was working two jobs. Life was good,” Sheppard says. But less than six months later, she noticed a patch of skin on her breast that seemed thicker than the surrounding tissue. It wasn’t quite a lump, but it was enough to get her to schedule a mammogram. The doctor also suggested a biopsy of the patch.  

Within weeks of that initial appointment, Sheppard got a call at work with the results. She had breast cancer. But as her oncologist at Mayo Clinic Arizona explained, the specific diagnosis was triple negative breast cancer, a rare, aggressive subtype that makes up only about five to 15 percent of all breast cancers.

Not only is triple negative breast cancer aggressive, behaving more like lung cancer, but it also tends to develop quickly and is not well detected by mammography. Despite Sheppard’s diligence about yearly screenings, her cancer wasn’t caught until it had already entered stage two of progression.

“Women may be doing everything right in terms of screening and monitoring and being healthy, but can still get breast cancers in between their regular screening mammograms,” says Dr. Karen Anderson, a researcher in the Virginia G. Piper Center for Personalized Diagnostics, part of the Biodesign Institute at Arizona State University. Anderson is also a medical oncologist at Mayo Clinic Arizona.

Part of the challenge with both diagnosis and treatment lies in the heterogeneous nature of breast cancer. It’s not simply one disease, but rather many different diseases that fall under the same general umbrella.  

“We know of at least seven or eight molecular types of breast cancer,” says Joshua LaBaer, director of the Piper Center.

For some of the more common forms of breast cancer, scientists have developed highly effective treatment regimens. For example, estrogen receptor positive cancers respond well to anti-hormone therapies, such as the widely prescribed Tamoxifen. Another common subtype is HER2/neu positive, which is often treated with a drug called Herceptin. But triple negative disease, the type Sheppard was diagnosed with, is not one of those cancers.

“You see the numbers in comparison with other forms of cancer that have survival rates that are much, much higher, and then to hear there’s no targeted treatment for it – to say it’s frightening is an understatement!” says Sheppard.

But there is a factor that will likely improve any cancer patient’s odds of beating the disease – catching it early on. LaBaer and Anderson are both studying early detection of breast cancer through identifying biomarkers, or antibodies in human blood that react with proteins the body produces when cancer is present.    

“The purpose of antibodies generally is to attack proteins from invading organisms or invading pathogens,” LaBaer says. “But in certain circumstances, people make antibodies against self-proteins.”

Cancer is one of those circumstances. Tumors cause the unregulated production of proteins, like an assembly line that suddenly runs out of control. The body recognizes the unnatural production and responds with antibodies.

While proteins may only remain in the bloodstream for a short time, the “memory antibodies” persist for much longer, making them easier to detect. LaBaer and Anderson both have projects underway to find out if certain antibodies give away the presence of breast cancer.

“We think that triple negative would be especially well-benefited from having an early detection method,” LaBaer says, because of its aggressive nature and poor prognosis. He is currently two-thirds of the way through a rigorous study screening blood from 150 patients, hoping to identify useful biomarkers. Anderson is coordinating a large study for the National Cancer Institute comparing 80 different biomarkers that have been identified by labs all over the country to find which ones are truly predictive of breast cancer.

“A lot of us believe very strongly in early detection because we know if you can catch the disease in stage one or even early stage two, you can do surgical removal, you can do radiation therapy and you have a better chance of success,” LaBaer says.

Early detection is a promising approach in the fight against cancer. But what if you could get a vaccine that would prevent you from ever developing the disease at all? That’s the vision of Stephen Albert Johnston, director of the Center for Innovations in Medicine at the Biodesign Institute.

“I decided I wanted to invent something to totally change the field,” Johnston says. A preventative cancer vaccine certainly would, but many doubted at first that such a thing was possible. The journal Nature even published an editorial piece calling Johnston’s idea a “misguided goal.”

“Everybody said ‘that’s impossible, you’re just blowing steam,’” Johnston says. But in looking where no one had looked before, he found something interesting. Despite the research showing each tumor is different, Johnston has found they also have some things in common.

“Let’s say this variant occurs in five percent of tumors and this one’s in ten percent of the tumors. You can start putting them together so it adds up to 100,” Johnston says. “Now we have the components that we think would go into the human vaccine to prevent cancer.”

Johnston’s team tested the vaccine in mice and found that it works. Now they face the challenge of showing it works in humans. The problem is that the efficacy of a cancer treatment depends on whether it extends a person’s life, which would take too long to measure.

“If you’re going to give a vaccine to healthy people, it could be 20 years before they get a tumor,” Johnston says. “How would you know if you did any good?” His solution? Give the vaccine to dogs. They get cancer at about the same frequency as humans, but live much shorter lives, making it more feasible to test the effectiveness of a vaccine on them.

“Our logic is that if we get a vaccine out there and it’s protecting dogs from getting tumors, it’s going to be hard for somebody to argue that we shouldn’t be using it on people,” Johnston says. He hopes to use crowdsourcing to help fund the project. If he is able to demonstrate that the vaccine works, Johnston’s idea is to give one to each investor from the crowdsourcing campaign to use for themselves – or their dogs.

Until a cancer vaccine becomes available, patients and their physicians must decide on the best possible treatment plan based on the person and the cancer. For many patients, including Sheppard, that plan often includes radiation therapy. Radiation relies on the presence of oxygen in the tumor tissue to work effectively. If there is a lack of oxygen in the tissue, an environment called hypoxia develops, which can allow the tumor to grow faster, spread to other organs and hinder radiation treatment.

Vikram Kodibagkar, a biomedical engineer in ASU’s Ira A. Fulton Schools of Engineering, is developing imaging technologies to detect and monitor hypoxia in tumors, including breast cancer. 

“We want to see quantitatively, as in getting a number that relates to how much oxygen is present, as well as qualitatively, trying to noninvasively paint the regions inside of the tumor that are hypoxic,” Kodibagkar says. “We have developed the technologies to do so and have demonstrated them in pre-clinical models.” This new method will potentially allow oncologists to predict how the course of personalized therapy will run and better understand how to treat tumors with hypoxic regions.

Nearly one in eight women in the U.S. will be diagnosed with breast cancer in her lifetime. But with early detection alone, Joshua LaBaer says there is potential to save thousands of lives. Certain subtypes are already considered to be very treatable, while others, like Sheppard’s triple negative disease, are less well understood.

However, her story has a happy ending. After receiving treatment at Mayo Clinic, Sheppard has been cancer-free for almost four years. By all accounts, she has beaten the odds.

“I am not in remission,” Sheppard says. “I am cured.”

Karen Anderson is an associate professor in the School of Life Sciences in ASU’s College of Liberal Arts and Sciences. Stephen Johnston is a professor in the School of Life Sciences. Joshua LaBaer is a professor in the Department of Chemistry and Biochemistry in the College of Liberal Arts and Sciences. Vikram Kodibagkar is an assistant professor in the School of Biological and Health Systems Engineering in the Ira A. Fulton Schools of Engineering.

Written by Allie Nicodemo, Office of Knowledge Enterprise Development