New approaches target aggressive breast cancers


October 31, 2013

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.” Download Full Image

“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

Allie Nicodemo

Communications specialist, Office of Knowledge Enterprise Development

480-727-5616

Division of household chores may depend on one's mess tolerance


October 31, 2013

Not that anyone is pointing fingers, but one individual went three weeks without noticing that dirty laundry had piled up.

The division of household labor is an issue that cuts across countries, genders and all types of relationships, from married couples to roommates. Trash Download Full Image

“This is one of the top three conflict issues couples fight over,” said Jess Alberts, Hugh Downs School of Communication President’s Professor. “Wives who feel like the division of labor is unfair are more dissatisfied and more likely to think of divorce.”

Strategies to cope are varied and inventive, said Alberts, who has conducted research on this issue for the past several years.

“This is the ongoing issue in my marital life and currently my favorite research project,” she said.

Inspiration to address this most basic issue with universal effects was inspired by ASU School of Life Sciences President’s Professor and entomologist Jennifer Fewell, who studies the division of labor between ants and bees.

"Fewell argued that ants and bees have specific threshold levels or tolerance for disorder in the hive. When they are bothered by their threshold level being violated, they are motivated to act,” Alberts said.

This realization inspired Alberts’ integrated theory of the division of labor that is currently in a testing phase and working “really well.” Her theory argues that people will act according to their threshold levels for household clutter or disorder.

“People possess a tolerance threshold for various tasks in the home. If one person has a low threshold for disorder, then the person with the higher threshold may never do anything because his or her threshold is never reached. Through repetition, the person with a lower threshold becomes more experienced and better at it,” she said. “Usually, the person with a lower threshold is not willing to wait for the person with the high threshold to be motivated to act.”

Women typically tackle the majority of chores and evolutionary psychology research explains why this may occur. For example, research shows that although parents equally respond to a baby in clear distress, they often vary their pattern if the baby is merely fussy. If mom responds faster to a fussy child, this becomes a reinforced pattern in which mom becomes the only one tending to the baby, Alberts said.

“Research suggests that females do about 50 percent more of household chores than males. Some people say it is an economic issue, but even when the woman makes more money, often she still does more housework. Sometimes the woman does more labor even when the husband is retired,” she added.

If you’ve ever felt unappreciated for handling the housework, consider the “economy of gratitude” that refers to the fact that people are grateful for gifts when they are in a relationship. However, gifts are defined as receiving something more than is expected. If one person does a task all of the time in a relationship, then their effort is not seen as a gift. Yet, if the other partner does the task only occasionally, they expect to be thanked for doing it because they see their contribution as a gift, or something added.

“It’s kind of like adding insult to injury,” Alberts said.

In a survey they conducted, Alberts and former graduate student Justin Boren found that gay couples have an easier time in general with the division of labor because they talk about it more readily. Female roommates also talk about chores while male roommates typically don’t. Instead, males may resort to passive-aggressive techniques, such as piling dirty dishes on someone’s bed.

“Some men with a low threshold level expect women to do most of the household work and are bothered because their partner is not motivated to do so. This expectation may come from the fact that, for social and evolutionary reasons, women pay more attention to and have more awareness of detail. They also have a keener sense of smell,” Alberts said.

Kendra Knight, a former ASU graduate student, measured individuals’ threshold levels by showing them a series of increasingly messy photos to discern at what point they would be motivated to act. Knight’s work is being recognized at the National Communication Association Convention in November when she will receive the Gerald R. Miller Outstanding Dissertation Award.

How does one avoid the chore trap?

“At the beginning of a relationship, try not to do a task more than three times in a row, if you don’t want be seen as owning the task,” Alberts advises.

If someone has a lower threshold for messes, thank your partner for their efforts.

“If you don’t feel that your partner is grateful for your efforts, especially if you perform the lion’s share of domestic labor, that’s likely to exacerbate feelings of inequity and dissatisfaction, making a difficult situation even worse,” according to an article in The Greater Good that Alberts co-authored with Angela Trethewey, Hugh Downs School of Communication director and professor.

Keep in mind that some people are simply oblivious until it reaches a crisis point, such as when someone runs out of underwear after three weeks.

“If it doesn’t trigger your threshold, it doesn’t register,” Alberts said.