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Survivor, Researcher Join in Quest for Breast Cancer Cure

By Karen Fleming-Michael
Special to American Forces Press Service

FORT DETRICK, Md., Oct. 20, 2003 – When the Defense Department took on the task in 1992 of helping to find a cure for breast cancer, it forged relationships spanning science, academia, survivor support groups and the military.

Two "military" women involved with breast cancer research under the Congressionally Directed Medical Research Program have never met. But retired Col. Charlene Holt's experience as an oncologist and breast cancer survivor and Dr. Marti Jett's expertise as a researcher link the two women who would like nothing more than to find cures for the cancer that in 2002 struck about 203,500 women and killed about 40,000 more, according to figures from the American Cancer Society.

"Consumers like Dr. Holt continue to infuse the CDMRP with passion, inspiration and vision," said Col. Kenneth Bertram, an oncologist and director of CDMRP. "Scientists and clinicians like Dr. Jett are our greatest hope for preventing, controlling and curing these diseases."

Holt, a pediatric oncologist trained at St. Jude's Hospital in Memphis, Tenn., spent most of her Army Reserve and civilian careers setting up hospital oncology programs in Colorado, Idaho, Texas, Panama and the United Arab Emirates, and teaching her specialty at several universities.

Because both of her grandmothers had breast cancer, Holt said, she knew she was at high risk for the disease. Though mammography was in its infancy, she routinely had mammograms and conscientiously lugged her films with her wherever she went. Mammograms taken in 1987 and 1988 were clear, but in 1989 she noticed a dimple on her left breast.

A biopsy revealed a malignancy, which led to a modified radical mastectomy. When confronted with her diagnosis, she did what she knew best.

"I studied breast cancer and decided to get a second opinion on my mammography films," Holt said. The second look revealed not only the tumor that was missed on the left breast, but also showed she had tumors on the right breast as well.

"Whatever I did and whatever decisions I made, I researched them -- especially because things were initially missed," she said. "I even told the surgeon where to insert the needle for the biopsy."

Forty-five days after her first mastectomy, she had a second one on her right breast.

Two years after her surgeries and with her cancer in remission, Holt received a call to join the staff of Madigan Army Medical Center in Tacoma, Wash. There, she developed a multidisciplinary breast clinic so the surgeon, radiologist and oncologist could meet with the patient and her family to discuss the options and make a joint decision on treatment.

She also started a project to detect the two genes known to predispose women to breast cancer. The staff's efforts at Madigan led to the best early detection rate in the state of Washington and the Army, Navy and Air Force, she said.

Holt didn't want other women at high risk for breast cancer to feel alone, so she became a regular with Madigan's breast cancer support group and an advocate for the American Cancer Society. Her experiences led to an invitation to review breast cancer research proposals up for funding through CDMRP, which took the initiative to include survivors on review panels from its beginning.

Though an oncologist, she wore her survivor hat when reviewing research proposals and was also asked to educate other patient advocates who were starting on what they could expect in the review process.

"For the first time, basic scientists who sit at their benches and do 'lab rat' medicine realized why they were doing it with the involvement, face to face, on a committee with a woman (survivor) asking questions," she said of the survivor's role in the review process. "So many of the scientists hadn't been involved in clinical medicine and the reality of what it was all about."

Giving clinicians, researchers and consumers a voice in the grants review process is vital for balancing the program, said Dr. Rick Kenyon, program manager for the Breast Cancer Research Program. Many of the clinicians involved in the review process are also researchers, holding both medical and doctoral degrees, so they can interface with the researchers.

"On top of that, we have the consumer who can say, 'Hey, you're not going to do that to me,'" he said. "Consumer reviewers nicely complement the science and put in perspective how we're going to proceed and how the money is going to be spent."

Holt said she is encouraged about the future of breast cancer research. "As we understand molecular biology and molecular genetics, the therapeutics of the future are going to be far more specific than they have in the past," she said.

"What the new generations are going to have to figure out, at least from a clinical standpoint, is how you combine the chemo that we have now with the new biotech and how to combine the new molecular drugs and genetic profiles of patients together to do the best thing," Holt added.

One researcher making strides in those areas is Dr. Marti Jett from the Walter Reed Army Institute of Research in Washington, D.C. A biochemist who has researched mechanisms that apply to both breast cancer and biological threats since graduating with her doctoral degree from Georgetown University, Jett was one of the first researchers to receive a grant from CDMRP when its Breast Cancer Research Program began in 1992.

With the four-year grant money, she hired breast cancer researchers and tried to understand the effects a set of signaling molecules has on drug-sensitive and multi-drug resistant cells. Collaborating with the National Institutes of Health, the team helped point out to the world that the fatty acid binding proteins associated with normal cell function disappear with cancer while other fatty acid binding proteins increase. They also discovered that antisense therapy to block production of the latter fatty acid binding proteins destroys the tumor.

A patent was issued, papers were published, and Jett's idea led to two additional CDMRP grants.

"I think we have leveraged that money so well," she said. "It has not only provided really important, very basic information about fatty acid binding proteins, but it's benefited all our projects so much."

A third grant from the Breast Cancer Research Program is helping to grow more breast cancer researchers. With a training grant, she is now pairing with Howard University to determine why breast cancer presents itself more severely and earlier in pre-menopausal women of African American descent than their Caucasian counterparts.

Jett's research not only has advanced breast cancer research, but also has helped military medicine.

"My work with biothreat agents meant looking at similar mediators. It seemed to me that if I could do basic research in one system to understand what is regulating them, it would help at looking at the biothreat pathogens that I was examining. Indeed, that is exactly the case," Jett said. "Much of the work we did on the first breast cancer grant has led to some major findings in terms of novel ways of diagnosing exposure to biothreat agents. It was just a wonderful mix of chemistry."

Will some of the answers about cancer be found within a military lab? Jett says it's possible.

"Nowadays, research is so complex and people are forming such big groups to include expertise so, yes, it wouldn't surprise me at all if some technology developed in a military lab could directly contribute to improvements in treatment with cancer," she said.

Holt said she's encouraged by the work CDMRP researchers like Jett have accomplished. "When I started with St. Jude, the average child was dead in four months with leukemia, and now I get Christmas cards from kids 20, 30 years out," she said. "I think the same thing is going to happen with all cancers as we understand the mechanisms, which is why I think this program is important."

Now retired from Madigan and the Army Reserve and working as a consultant for a drug company, Holt continues to be a fan of the CDMRP process.

"It shows how the Army is a 'can do' organization. Whether it's taking a hill or winning a war ... you give them a task and they put together a lot of different skills and talent and make it happen," she said. "They've set a unique standard for the rest of the medical world to take a long hard look at."

(Karen Fleming-Michael is a staff writer for The Standard.)

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