U.S. Army Medical Research and Materiel Command
Point of Contact:
Chuck Dasey, (301) 619-7071
July 20, 2000
For Immediate Release:
Minimally Invasive Approaches Characterize Innovative Techniques for Early Detection and Treatment in Breast Cancer
Research Results from "Era of Hope" Department of Defense Breast Cancer Research Program Meeting
ATLANTA, June 10, 2000 - New technologies described at the "Era of Hope" Department of Defense Breast Cancer Research Program meeting feature minimally invasive procedures and promising approaches that could change standard practices in breast cancer screening and treatment.
Screening Breast Duct Fluid May Identify Atypical Cells Before Cancer Develops
Research presented today identifies a new technique that may allow clinicians to obtain cells from the same breast ducts over time, which could make it possible to determine the presence of pre-cancerous abnormalities in high-risk women, potentially years before mammographically detectable lesions develop.
"Scientists have known that all breast cancers arise in the lining of milk ducts, but until now, routine sampling of ductal cells - a logical approach to detection of atypical cells that are often precursors to cancer - has been impeded by two obstacles. One was a map of the ductal system and the other was the development of a minimally invasive device to withdraw cells from the ductal lining," said lead investigator Susan M. Love, M.D., adjunct professor in surgery, University of California at Los Angeles, CA.
Dr. Love's team tackled both obstacles. First they constructed an anatomical diagram of breast ducts, based on examining nipples of lactating women (volunteers found through La Leche League), archival ductograms (X-ray images), and breast tissue from mastectomies. These studies demonstrated that each breast has an average of five to nine unconnected milk ducts that extend from the nipple area back to the chest wall, a pattern that holds true across differing populations. "Contrary to prevailing views, the breast is actually a collection of ductal systems, not one organ," explained Dr. Love.
She and her colleagues then developed an early-generation device - a double-lumen catheter - to retrieve ductal cells. Each of its two lumens is a minute thread (less than 0.5 mm in diameter), that is inserted a short distance (roughly 0.5 inches) into the natural duct opening in the nipple area - eliminating the need to puncture the skin. A saline solution is injected through one thread and fluid containing cells from the lining is aspirated through the other thread in a process called "ductal lavage." Dr. Love notes that women generally report less discomfort than during a mammogram.
"With this device, we can find cells that are just thinking about becoming cancer," Dr. Love said. That includes pre-cancerous cells known as atypia, as well as malignant ones, before they break out of the duct system and become full-fledged invasive breast cancer. Scientists have long believed that even the tiniest tumors visible on mammograms have been growing for at least eight to 10 years.
Independent investigators at 19 major breast cancer centers in the U.S. and Europe recently completed a multicenter clinical trial involving 502 women at high risk for breast cancer, ranging in age from 26-81years. In this study, a later-generation device was compared to a procedure in which a suction cup draws out ductal fluid. Preliminary findings on a subset of the 502-woman cohort show that in the 271 breasts lavaged, the new device identified abnormal cells in 15% of the population (41/271), compared with approximately 4% in the comparison group (11/271). Dr. Love will discuss additional data from the clinical trial at the "Era of Hope" meeting. This research initiative was initially funded with a Department of Defense Breast Cancer Research Program "IDEA" grant, an award category designed to support novel, untested and high-risk ideas, as well as the participation of young, promising scientists.
The device has been cleared for marketing in the U.S., has a patent application pending and will become available at key breast cancer centers in the fall. "This technique isn't widely available yet - more doctors need to be trained. But it should be available at local breast cancer centers soon," said Dr. Love.
Dr. Love is one of the founders of a privately held company that is commercializing the catheter, and currently acts as a board member and consultant to the company.
Test for Tumor Markers May Flag Women with High Potential for Metastasis
In another presentation made here, researchers reported on a testing system that can detect tumor markers in the blood of breast cancer patients, which may predict future risk for metastasis. These findings are a first step toward the goal of being able to diagnose and treat cancer metastases before a detectable tumor forms.
"We hope that this test will allow us to identify patients who are at high risk for disease recurrence," said Bret Taback, M.D., department of molecular oncology, John Wayne Cancer Institute, Santa Monica, CA. "If our approach is validated, it will mean that a simple, minimally invasive blood test can identify the spread of disease while it is occurring and before the disease is clinically detectable by conventional methods." According to Dr. Taback, by providing the oncologist more information about what the patient's cancer is doing, the results of this test could also be used to help make decisions about the most appropriate adjuvant therapy for an individual patient.
The researchers used electrochemiluminescent technology combined with a new ultra-sensitive detection instrument developed by a private company to detect one or more of four tumor markers that are known to be expressed by breast cancer tumor cells. They performed the test on blood drawn from 65 patients recently diagnosed with breast cancer (49 with stage I or II cancer, 16 with stage III or IV). Blood samples from 45 patients (69%) showed the presence of at least one of the four molecular markers. Markers were associated with tumor size and disease stage - that is, patients with tumors of a certain size were more likely to have certain markers detected in their blood. This research initiative also received funding from the Department of Defense Breast Cancer Research Program "IDEA" grant.
The patients are being followed long-term to see whether the presence of certain markers accurately predicts metastasis or disease recurrence. Because expression of tumor markers varies widely among patients and within tumors in the same individual, it can be difficult to discern the significance of the presence of any single marker, explained Dr. Taback.
"By testing for multiple markers, we are casting a bigger fish net. We hope that further follow up will tell us whether patients with a particular marker or unique combinations of markers have faster recurrence or a poorer prognosis," said Dr. Taback. He and his colleagues are also refining the test to detect other markers that might be better at predicting the risk of metastasis or disease recurrence.
The presence of tumor cells in the blood can mean different things depending on the stage and status of the patient's disease, Dr. Taback said. In early-stage disease, tumor cells in the blood most likely indicate a spread of the primary tumor (metastasis). In more advanced-stage disease, the presence of these cells may indicate a more rapidly progressing disease.
Laser Treatment Could be Alternative to Surgery for Some Women
An experimental laser treatment for small, localized breast cancer tumors could become a less-invasive alternative to lumpectomy for some patients, researchers reported today.
The success of the laser procedure presently hinges on whether magnetic resonance imaging (MRI) can reliably detect any small areas of cancer not destroyed by the laser, which is the focus of the research being conducted. To date, about 100 patients in London, England, and Little Rock, AR, have received the experimental laser treatment; some were treated in another study.
"The advantage of laser treatment is no surgery, no scar, and no change in the size or shape of the breast," said Professor Stephen G. Bown, director of the National Medical Laser Centre in London. "It would be a much simpler procedure to do, with a lower risk of complications, and no hospital admission required in patients who are otherwise generally fit."
Before the laser treatment, patients have a diagnostic MRI scan. Then, under image guidance, thin needles threaded with optic fibers are inserted into the tumor via the skin, followed by the delivery of low-power laser light to gently heat and kill the tumor tissue. After the laser treatment, patients have a second MRI scan, at which time the researchers assess whether any areas of cancer can still be detected. Patients then undergo conventional surgery to remove the entire cancer area in the breast. Following surgery, excised tissue is examined under a microscope and compared with the MRI images.
Dr. Bown and his colleagues found good correlation between the post-laser MRI images to see if the imaging picked up any areas of cancer not adequately treated with the laser. The investigators report good correlation between the post-laser MRI images and clinical measurements of the surgical specimen for both the true extent of the cancer and the extent of laser-induced destruction.
In the study's next stage, which is just getting under way, patient volunteers will receive only the experimental laser treatment without subsequent surgical lumpectomy, but with close MRI follow up.
According to the researchers, laser treatment could be a suitable alternative to lumpectomy only for carefully selected patients with small, localized breast tumors. Dr. Bown emphasized that it should not be considered at all if doctors have any suspicion that a patient's cancer has spread (for example, to the lymph nodes).
"Era of Hope" is a forum for the presentation of research supported by the U.S. Department of Defense's Breast Cancer Research Program (BCRP), an unprecedented partnership between the military, scientists, clinicians, and breast cancer survivors. Since 1992, the BCRP has been working to prevent and cure breast cancer by fostering new directions in research, addressing underserved populations and issues, encouraging the work of new and young scientists and inviting the voice of breast cancer survivors to be heard in all aspects of the program. One of 53 congressional research programs managed by the U.S. Army Medical Research and Materiel Command, the BCRP has received more than $1 billion to date from Congress for innovative breast cancer research.
"Development of Intraductal Techniques for Breast Cancer Prevention, Diagnosis and Treatment"
Susan M. Love, Jean Chou, Regina Offodile, Mary Alpaugh, Eufrosina Traipe, Stella Grosser, Sharon Hirschowitz, Sanford Barsky
- Poster Session: Friday, June 9, 6:30 p.m. - 8:00 p.m., Galleria, Posterboard R-12
"Molecular Detection of Metastatic Cells in the Blood of Breast Cancer Patients"
Bret Taback, Arden Chan, Christine Kuo, Duc-Hanh Nguyen, Armando Giuliano, Dave S.B. Hoon
- Poster Session: Friday, June 9, 6:30 p.m. - 8:00 p.m., Galleria, Posterboard C-9