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Faculty Profile

Peter Lee Charts New Territory in Breast Cancer Research

By Mitzi Baker

Peter Lee, MD
  Peter P. Lee, MD

In his first six years on the faculty, Peter P. Lee, MD, had devoted most of his time to research on the role of the immune system in melanoma and leukemia, with some HIV studies on the side.

He had only recently turned his attention to breast cancer on the day in the spring of 2005, when he saw a flyer announcing a $4 million grant for breast cancer research. So he didn't think he was a likely candidate—even when he saw it was targeted to young researchers who could bring fresh ideas to the field. "I didn't think I had much of a chance, but the grant was a dream, so I figured what the heck," he said.

In March, Lee, assistant professor of medicine (hematology), received the first installment of the grant from his Era of Hope Award, and it was testimony to the potential other scientists see in his approach to research: He seeks to apply the expertise he has developed in immunology, starting with his work as a first-year medical student on T cells and AIDS, to developing new tools in the fight against breast cancer.

Already his tack is yielding tantalizing results: He published findings last fall that showed his method of using immune cells to predict the severity of a woman's breast cancer could be more effective than the current method of looking at cancer cells.

"He has discovered a new and unexpected way to predict progression of disease in breast cancer patients," said Philippa Marrack, PhD, a researcher at National Jewish Medical and Research Center in Denver. "This could radically change the way the disease is treated in different patients."

Not your ordinary grant

Yet it would be a mistake to see Lee's award as strictly the result of the publication of those findings, which was months after he applied for the honor.

The U.S. Army Medical Research and Materiel Command, which manages the grant program, is different from the usual medical research funding programs in that its application for the Era of Hope Award was not asking for a proven track record in breast cancer research or mountains of supporting data. Given that the award is targeted for young researchers who have no more than six years in their first academic appointment (Lee made the cut-off by one month), the Army's decision in large part is based on their assessment of the character of an applicant—and his or her thinking about research.

"The selection process for this is completely different," said Lee. "It's about the person." For a chance at winning one of five allotments of $4 million from a pool of 70 candidates, Lee had to put words onto paper explaining his research philosophy—why he does what he does—much like the personal essay in a college application.

In his essay, Lee discussed how he has long had an appreciation for the intricacies of the immune system and the many ways it can go awry. He described how the emergence of the HIV epidemic sparked his scientific creativity. In 1986, after his first year of medical school, Lee convinced a faculty member to allow him to pursue a project he had begun as an undergraduate majoring in microbiology—creating antibodies that would block one of the molecules that HIV needs to enter T cells. He managed to raise the antibodies, but couldn't show that they worked. One year later, an article was published using this exact approach, but with a more effective antibody.

"I had the right idea, but wrong antibodies," Lee wrote in his proposal. "But rather than discouraging me, this near-miss experience instilled in me a great appreciation for science, research and the immune system. I was hungry to come up with more innovative ideas."

After completing medical school and a residency in internal medicine, the lure of the mysterious immune system was still strong for Lee; he chose to pursue fellowship training in immunology and hematology. In his clinical training, he cared for leukemia patients who suffered through the course of their treatment and ultimately succumbed to their diseases.

Their plight inspired Lee to try to come up with better treatment approaches than chemotherapy, which can ravage the entire body. "I have long felt that the best opportunity for a specific, non-toxic therapy for cancer would be to harness the specificity of the immune system," he wrote.

And that's what encouraged him in 1996 to enter the field of tumor immunology. At that time, he explained, the conventional wisdom was that the immune system ignored cancer because it was recognized by the body as "self." He wanted to challenge this notion, reasoning that an alternative scenario could be that anti-cancer immune responses do develop in patients, but they are ineffective.

Lee's findings were the first to show anti-tumor activity in melanoma patients' T cells and that the cancer had caused the cells to malfunction. The findings opened up new territory for speculation and investigation; published in 1999 in Nature Medicine, this article has been cited in other publications more than 450 times.

Another perspective on breast cancer

Since then, Lee's lab has investigated further the molecular mechanisms for T cell dysfunction in cancer patients. He recently expanded its scope to include looking at the immune cells found in the lymph nodes surrounding breast cancer. In September, Lee published a study showing that unique patterns of immune cells in the lymph nodes of breast cancer patients could divide the women neatly into favorable and unfavorable outcome groups.

Lee seeks to open a whole new way of viewing breast cancer, from the immune system's point of view rather than the cancer cell's. On a clinical level, his findings could result in a simple tool—a stained biopsy sample—that could give valuable prognostic information. Doctors could begin using this test immediately as it takes already-available methods but applies them in a new way.

Additionally, his work could lend valuable insight into the delicate balance between cancer and the immune system that determines clinical outcome.

"Can we really understand the mechanisms by which breast cancer suppresses immune response," Lee wonders, "and can we potentially devise new treatment approaches that could block or reverse these changes either systemically or more interestingly, directed at these tumor-draining lymph nodes?"

Along with his thinking about research, another thing that worked in Lee's favor was the grant's stipulations that the money be used for interdisciplinary work. That's no problem for Lee, said Lee's boss, Linda Boxer, MD, PhD, the chief of the division of hematology who nominated him for the award. "He is creative and innovative," she explained, "and is able to assemble collaborators from different fields to help solve problems relevant to clinical medicine."

Since winning the award, he has established a team of statisticians, computer scientists and clinicians to use novel biostatistical methods and computational modeling to integrate their findings into an all-inclusive model.

"The scope of this award allows me to envision such a comprehensive and multidisciplinary approach to breast cancer," wrote Lee in his proposal. "I am dedicated to bringing this vision to reality."

And what that means to Lee is doing translational work—research that can lead to direct benefits for patients.

"Dr. Lee's discoveries suggest new ideas about how the immune system interacts with breast cancer, ideas which may help us treat the disease more effectively," said Marrack, the senior Colorado scientist and Howard Hughes Medical Institute investigator who is an internationally renowned immunologist. "He is one of my heroes: He takes on problems in patients rather than tiptoeing around the issues in mice and model systems like many of the rest of us."

Posted: 07/21/06

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