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A Big Battle at the Smallest Levels

By Jennifer Dublisky '11

Annamarie Widener will never forget the second day of 2001.

While celebrating the New Year with a girlfriend, Annamarie, then 38, leaned over a table to hear her friend more clearly when she felt a lump in her breast. A regular at giving herself monthly check-ups, the size of the lump alarmed her. She scheduled a visit to the doctor. Two days later he told her, "You are too young to have breast cancer. You don't have a family history—it's probably a cyst." He sent her home with the recommendation to take vitamin E.

Dr. Bin WangStill wary, Annamarie sought a second opinion from a general surgeon a friend recommended. The surgeon scheduled an immediate biopsy and removal. A week later doctors revealed that she had breast cancer rated as Stage 2B/3 estrogen negative Her2/Neu; level 3+—the highest level of this form of cancer. "His immediate reaction saved my life," said Annamarie. "The cancer would have taken over my whole body within months."

Doctors believed her aggressive form of cancer would not respond well to a standard chemotherapy regimen, so they prescribed an aggressive course of treatment using multiple methods. Thus began 18 months combining chemotherapy, radiation, and a new drug known as Herceptin. With her two children—Jim, then a junior in high school, and Deanna, in eighth grade—Annamarie, a Yardley, Pa., resident who works in payroll management, had a challenging path as a wife and mother. She persevered through her treatments trying to keep everything as normal as possible for her family. Despite the severity of her breast cancer, the treatment went well but the threat of reoccurrence was always with her. "You still have the fear that it could happen and you think about it every day," she said. "Soon after my treatments my doctor asked me to build a five-year plan for my family—'in case.'"

Part of that plan was getting her children through college. She and her son Jim, now a 2006 graduate of Widener, made their first visit to the Main Campus shortly after she finished chemotherapy treatments. "I remember visiting Widener University and thinking that my son would be safe," she said. "It offered a family atmosphere where all of the professors would get to know him. It comforted me knowing that he would be receiving an education."

Cases like Annamarie's are far too prevalent. Breast cancer is the most common cancer in American women—one in eight women will develop breast cancer—and the second leading cause of cancer death for women. The impact of the disease has been felt by others in the Widener University community. Dr. Barbara Kay Toner, 52, of Mount Laurel, N.J., died of breast cancer shortly after completing her doctoral work in Widener's Center for Education in 2010. In November, Rebecca L. (Caltabiano) Cancila, 38, of Mullica Hill, N.J., a 1996 nursing graduate, died after battling the disease.

Developing treatments that cure breast cancer is the goal of Dr. Bin Wang, a Widener University assistant professor of biomedical engineering who joined the faculty in 2011. Wang's research is supported by a $450,000 grant from the Susan G. Komen for the Cure foundation for a three-year project he started while teaching at Temple University in 2010. His research strives to develop a drug delivery system to overcome resistance to chemotherapy in breast cancer patients.

Chemotherapy, the most common treatment for breast cancer, is given intravenously and is known to be very toxic, causing severe side effects. Some patients can become "chemoresistant," meaning that once a tumor is treated with the drug, it builds resistance and therefore cannot be treated effectively with chemotherapy again. "The scary truth is that there is nothing currently available to breast cancer survivors who have to face recurrence and become chemoresistant," he said.

Wang and his research team are currently growing cells to treat with chemotherapy so that they become resistant. He will then use nanoparticles—microscopic particles—to deliver drugs to the cells. (Nanotechnology is the use of particles consisting of a small number of atoms or molecules—a scale normally measured in nanometers, or billionths, of a meter.) "We always deal with something we can see; however, there are different phenomena that can happen when you study something so small," he said. "In my research, I have found that an injection of medication through nanoparticles goes through cells into the tissue and can stay in the blood for a long time, protecting the drug while traveling to the affected cell."

Currently, doctors use liposomes—essentially tiny, manmade bubbles—which are filled with chemotherapy drugs and then injected into the body to identify the tumors and release the drug. The downside of this method is that drugs often damage other parts of one's body, specifically "good cells," said Dr. Curtis Miyamoto, chairperson and professor of the Department of Radiation Oncology at the Temple University School of Medicine. "There is always a race to get more chemotherapy into the cancer without hurting the person too much, which is why the potential for this kindof delivery system is very great."

Initial response rates of breast cancer to chemotherapy are often encouraging; however, a majority of patients often see tumors progress seven to ten months later. "These cancer cells eventually become resistant to normal doses of traditional chemotherapy and continue to grow and ultimately kill the patient," Wang said.

If the cancer is discovered late, recurrence can become more common in breast cancer survivors, causing many affected cells to become resistant. Wang said once a cell is resistant, chemotherapy is no longer effective and the five-year survival drops to well below 50 percent of patients.

A targeted delivery system, like the one Wang is proposing, would be more effective and not only benefit those who become resistant, but also anyone being treated with chemotherapy. "Ideally in 20 years we will be able to inject nanoparticles and kill all tumor cells," Wang said. "They will be like small robots in our bodies defending our good cells, and only harmful cells will be destroyed."

Dr. Sabitha Pillai-Friedman, assistant professor of human sexuality at Widener and a certified sex therapist, is a breast cancer survivor who speaks frequently with other survivors. She said that most breast cancer survivors suffer from anxiety about recurrence. "This fear can be more intense for women who do not have a lot of treatment options," she said. "A targeted multi-drug delivery system to overcome chemo-resistance, like the one that Dr. Wang is working on, would be a gift to women with those types of cancers."

Pillai-Friedman believes that a targeted delivery system of chemotherapy can benefit all breast cancer survivors. "Most patients that I treat in my practice are emotionally devastated by the side-effects of chemotherapy," she said. "Side effects such as hair loss, drastic weight changes, and skin problems contribute to altered self-image. This method of delivery could reduce side effects, subsequently reducing the emotional, psychosexual, and relationship problems that breast cancer patients and their partners face."

Miyamoto also sees great potential in Wang's research. "This is going to make a difference in people's lives," he said. "The way we treat cancer will change because of people like Dr. Wang. He is trying to make a difference that will impact the future."

Annamarie, now an 11-year survivor, is in complete remission. After she made it through the first five years and beat the statistics, she revisited her five-year plan. "I am fortunate not to have had a recurrence, since the likelihood that I should have was high," she said. "In the beginning every morning you wake up thinking I'm a cancer patient—you realize you are not immortal, but the further you go away the easier it becomes."

Her son Jim vividly recalls his mother walking onto Memorial Field at Widener for his commencement in May 2006. "I considered myself lucky to have my mom at graduation after everything that she had gone through," he said.

Annamarie said attending his commencement "signified two things: My son was a college graduate and...I survived."