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Beyond microscopes and mortality charts, UF scientists are improving the outlook for many breast cancer patients
By Arline Dishong
A new case of breast cancer is diagnosed in the United States every three minutes (180,000 annually), and a woman dies from the disease every 12 minutes (44,000 annually). One out of nine women will develop breast cancer in her lifetime. Frightening odds for a disease which threatens such a major part of female sexual identity.
But as the 20th century draws to a close, there is reason for optimism - Diagnostic tests and treatments are being refined and scientists now are targeting cancer at the molecular level.
Many promising technologies for breast cancer detection and treatment are under investigation at the University of Florida Health Science Center's campuses in Gainesville and Jacksonville.
Physician scientists at both campuses are demonstrating the effectiveness of new computer-driven breast imaging, diagnostic and treatment techniques; better-targeted radiation therapy; and new combinations of high-dose chemotherapy, growth factors and bone marrow transplants. UF specialists also have helped refine breast conservation surgery and breast reconstruction.
In the laboratory, scientists conducting pioneering studies using mice with human forms of breast cancer are just beginning to assess the effectiveness of gene therapy.
UF pathologists are working to identify biological markers that can predict breast cancer's behavior before the disease can be found through standard breast examination or mammography.
Sentinels of Success
Based on discoveries concerning the way in which melanoma (the worst form of skin cancer) initially invades a specific "sentinel" lymph node, UF breast cancer specialists are now investigating the key lymph node first invaded by breast cancer. They anticipate that if this sentinel node is found to be free of cancer, there may be no reason to remove additional lymph nodes.
If long-term studies substantiate the accuracy of sentinel node biopsy, thousands of women each year will be spared the invasive procedure known as axillary dissection, in which 10 to 15 lymph nodes are surgically removed. Among the side effects of this surgery are nerve damage, swelling, reduced shoulder movement and pain.
"In my opinion, sentinel node biopsy may be one of the major advances in the care of breast cancer patients," says Dr. Edward Copeland III, director of the UF Cancer Center in Gainesville and chairman of the College of Medicine's department of surgery. Copeland is editor or co-editor of seven textbooks related to breast disease and cancer surgery.
UF radiologists in Gainesville also have refined a computerized, non-invasive breast diagnostic and treatment system called digital stereotactic large-core needle biopsy. This procedure exposes patients to only about half the radiation used in conventional X-ray imaging and leaves no disfiguring scars. The smallest tumors can be viewed from multiple angles, and, in many cases, open surgery can be avoided.
Cancer surgeon Dr. Scott Lind reports that a three-year study of 117 breast cancer patients treated at Shands at UF revealed this technology to be faster, more accurate, less costly and more comfortable to the patient than standard needle-localized breast biopsy. The stereotactic images are obtained in seconds instead of minutes, and the details are digitally sharpened by computer. Lind says the procedure can be performed in an outpatient setting using local anesthesia.
"We've found that stereotactic biopsy, when indicated as an initial diagnostic procedure, is superior to previous biopsy procedures," says Lind.
"With stereotactic biopsy, we can pinpoint abnormalities in the breast as tiny as 1 millimeter, and, by using computers to 'map' the lesion, we can biopsy tissue too small to be felt," he adds.
UF breast surgeons are finding that stereotactic breast biopsy is comparable in accuracy to standard needle-localized breast biopsy. The latter procedure involves inserting a guidewire into the breast to locate a suspicious area and then cutting along the wire to remove tissue, which leaves scars.
Breast biopsy and tissue analysis also are being improved in other significant ways, including greater attention to the guidelines physicians follow in performing the procedures.
In Jacksonville, Dr. Shahla Masood, professor and associate chair of pathology, has refined the technique of fine needle aspiration biopsy, proven highly effective in detecting structural changes in cellular material. Working with a select group of breast cancer pathologists, she helped develop national guidelines for physicians who perform this kind of biopsy, which usually is combined with core biopsy (using a 14-gauge tissue-cutting needle to remove a core of tissue) and careful study of mammographic images to reach a definitive diagnosis.
"Fine-needle aspiration biopsy provides superior analysis of the cells, but the expert analysis of tissue resulting from core biopsy generally is more precise - most likely because pathologists are more familiar with how to interpret what they see in the core-biopsied tissue," says Masood, who also is associate dean for research at the UF Health Science Center/Jacksonville. "With both techniques, we are sampling only a portion of the abnormality in a small amount of tissue. Thus, it's very important to correlate the visual images obtained in mammography with the pathologists' findings using both biopsy techniques."
Transplants Prolong Life
The dilemma of chemotherapy is that the drugs used to destroy cancer cells also often destroy other vital cells in the process. Bone marrow happens to be most vulnerable to this damage.
By refining bone marrow transplant techniques, UF researchers have been able to more effectively replace bone marrow damaged by chemotherapy. Key to the treatment is the use of stem cells, which give birth to all blood cells.
Doctors remove stem cells from the patient's blood and subsequently inject them back into the patient. The re-infused stem cells travel directly to the marrow, where they generate a fresh supply of healthy blood.
"We call this procedure stem cell rescue, since it enables patients to withstand high doses of cancer-killing drugs," says Dr. John Wingard, a medical oncologist with UF's College of Medicine. "Larger amounts of these drugs result in better response by the patient, including longer cancer-free survival."
"The problem," Wingard says, "is that when we increase the chemotherapy, we run into greater toxic effects on normal body tissues.
"Toxicity has been the major obstacle to escalating the dosage of anti-cancer drugs, and thus the transplantation of stem cells is needed to offset these adverse effects," he says.
Breast cancer now tops the list of diseases treated by bone marrow transplantation - following successful use of this procedure in patients with leukemias and other blood cancers, Wingard says.
"Since we extended the treatment to breast cancer patients during the past five years, we've seen a number of significant advances," including:
"Now we're evaluating the transplant therapy to women whose cancer has spread into four to nine lymph nodes. These patients face a 50-percent risk of cancer recurrence within five years if they receive only conventional chemotherapy," he says.
Testing New Technologies
UF's Cancer Center in Jacksonville is an active clinical testing site for promising new breast cancer detection systems, treatment refinements and investigations of plaguing questions about the greater threat faced by black women.
Center Director Dr. Gary Bowers cites a variety of exciting initiatives:
Despite the discovery in the mid 1990s of two genes that play a role in heightening susceptibility to breast cancer, gene therapy remains an elusive goal to medical scientists.
Yet there are grounds for hope - not through replacement of these genes in malignant cells, but possibly by giving the patient an influx of genes that activate natural immune responses against abnormal cells. This promising approach is now the subject of pioneering studies in mice with implanted human breast cancer - solid tumors large enough to be felt in standard hands-on breast examination.
Leading the experimental work is Dr. Lung-Ji Chang, associate professor of medical genetics and microbiology at UF's Gene Therapy Center in Gainesville.
"Because we want to obtain information that may be applied to people, we are treating human breast cancer in the animals and we're using human genes that are known to strengthen immune response to breast cancer," Chang says. "We have developed an excellent study model in these 'humanized mice,' in which to test how well various human immune-stimulating genes and combinations of genes help to generate immunity against breast cancer. The genes we're using have previously been found effective in eliminating tumor cells in mice.
"Our initial objective is to eradicate existing cancer, but the long-term goal is to develop a vaccine that will prevent the disease," Chang adds.
"We are designing a genetic approach that 'teaches' the immune system how to distinguish bad cells from good cells - by flagging the cancer cells with something that can be easily recognized by the immune system. Once the immune system is trained to recognize the cancerous cells, this recognition is stored in the cells' memory so that a permanent form of cancer resistance is created."
Chang faces critical questions regarding the promise of gene therapy. Among them: How much of the immune-stimulating genes are enough to generate resistance to breast cancer? And what is the most effective way to deliver the genes into the breast tumor?
Given the broad range of breast cancer research being conducted at UF, the idea of integrating the existing strong corps of talented professionals and resources into a well-coordinated breast disease center or institute is now the subject of serious discussions.
Dr. Gary Bowers, Associate Professor of Surgery, (352) 549-3939, gjb@traumaone.umc.ufl.edu
Jung-Li Chang, Ph.D.,Associate Professor of Molecular Genetics and Microbiology, (352) 392-3315, lchang@college.med.ufl.edu
Dr. Edward R. Copeland III, Director, UF Cancer Center; Edward Woodward Professor and Chair of Surgery, (352) 395-0622, copeland@surgery.ufl.edu
Dr. D. Scott Lind, Assistant Professor of Surgery, (352) 395-7973, lind@surgery.ufl.edu
Dr. Shahla Masood, Professor and Associate Chair, Department of Pathology, (352) 549-4387, sm@umc5.umc.ufl.edu
Dr. John R. Wingard, Professor of Medical Oncology, UF Cancer Center, (352) 846-2814, wingajr@medicine.ufl.edu
Shahla Masood Inspired by a friend's pain
The emotional pain of breast cancer crystallized for UF pathologist Shahla Masood 15 years ago when she diagnosed a cancerous growth in the biopsied breast tissue of a close friend with three children.
"I could see how, within seconds, my friend's life was shattered. The tumor was large and the lymph nodes were involved," Masood says of the woman, who underwent a modified radical mastectomy, radiation and chemotherapy.
Deeply moved by that personal encounter, Masood began to mobilize talents and resources locally and internationally to strengthen and expand patient-care services, research and education. Her efforts have helped improve information exchange among physicians and researchers in many parts of the world.
Masood described her friend's complex, emotionally draining experiences in the opening editorial for the premier edition of The Breast Journal, which she founded in 1993.
"Through this experience, I've gained a deeper appreciation for the psychosocial aspects of the disease, and of the pain and insecurity associated with the loss of a breast. I've also learned a lot about the uncertainties associated with the disease," wrote Masood, whose friend fared well for many years but now has cancer spreading into the bones.
The Breast Journal - the official journal of the American Society of Breast Disease, the American Society of Breast Surgeons and the Senolergic International Society - provides a panoramic view of advances in breast cancer research. Articles address medical, surgical, psychosocial and rehabilitative aspects of the disease. Nine internationally recognized breast disease experts serve as associate editors, and 95 additional specialists serve on the editorial board of the bi-monthly.
Masood also has organized and hosted an international breast disease symposium each of the last three years that brings world leaders in clinical practice and research to the Jacksonville-Gainesville area to share scientific findings.
Typically, Masood's commentary on breast cancer is comprehensive, and ambitious.
"Collectively, we as breast cancer specialists need to extend our expertise to improve the teaching of physicians and patients everywhere," she says. "We also need to create a vehicle for serving the medically underserved and find ways to motivate women to obtain diagnostic mammograms in a timely fashion. And we need to lobby for a universal low fee for mammograms and cervical tests."
Her appointment last year to the National Cancer Institute's Progress Review Group provides a platform from which she now can influence future directions in breast cancer research.
While many of Masood's efforts are global in scope, she also seeks to help medically underserved women in north Florida gain access to breast cancer screening and treatment.
For example, she introduced the Breast and Ovarian Cancer Risk Assessment Program to Jacksonville. The program is designed to assess the hereditary and non-hereditary risks for developing these two forms of cancer and to educate patients and their families regarding these risks.
Masood also is training "navigators" in the Jacksonville area to help educate low-income women and lead them to accessible health care. And, she is helping to develop a Jacksonville Research Consortium that will bring researchers from different medical centers together to identify important medical and research needs in the region and find ways to address them without duplicating services.
Under her leadership as assistant dean for research at the UF Health Science Center/Jacksonville, research funding increased 50 percent from 1996 to 1997. Now she is organizing a Center for Clinical Research to expand patient-oriented research and strengthen the teaching of research fundamentals to residents and fellows.
Masood and her husband, urologist Dr. Ahmed Kasraeian, have two sons enrolled at the University of Florida - Ali is a first-year medical student, and Sina is in pre-medicine.
Arline Dishong
Related web site: http://www.ufhscj.edu/path/breastj.htm