Just five years ago, there was no such thing as breast cancer prevention. Today, however, this new field of study holds much promise. A successful national study, revealing the ability of tamoxifen to decrease the incidence of breast cancer by up to 49 percent in high-risk women of all age groups, has given new hope and some sense of comfort to women and led to the discovery of other prevention strategies. Among these is a new large trial that will compare tamoxifen to another drug called raloxifene, of which the Johns Hopkins Oncology Center is a participant.

Called the STAR Trial for the Study of Tamoxifen and Raloxifene, the new multi-institutional project will compare and examine the two drugs in up to 22,000 women for effectiveness in breast cancer prevention.

Researchers believe both drugs, known scientifically as selective estrogen receptor modulators, work by selectively blocking the uptake of estrogen into breast tissue. Estrogen, a female hormone, can promote the growth of breast cancer. While the cancer-prevention properties of tamoxifen have previously been demonstrated through controlled clinical trials, this is the first breast cancer trial for raloxifene. Raloxifene, FDA approved for the treatment of osteoporosis, is suspected to be useful in preventing breast cancer because of the decreased incidence of the disease observed in over 10,000 postmenopausal women taking the drug as therapy for the bone disease.

This new study, headed by the National Surgical Adjuvant Breast and Bowel Project (NSABP), will include women at increased risk of developing breast cancer, women who are 35 years or older, and postmenopausal women. The women will be randomly chosen to take daily doses of either tamoxifen or raloxifene for five years, followed by seven years of physical exams, routine medical tests, and personal and telephone interviews by a STAR Trial physician or nurse practitioner. Data from the study will allow experts to compare the drugs, including side effects, and to evaluate their overall ability and benefits in preventing the occurrence of breast cancer.

Women who meet the study criteria for cancer risk, age, and menopausal status may call the Johns Hopkins Breast Center STAR Trial coordinator at 410-614-STAR (7827). (Note: As of press date, this trial is not yet open for accrual, please call the above number for more information.)

Dissecting the Cancer Instead of the Woman:
Sentinel Node Biopsy Provides New Way of Detecting Invasive Breast Cancer

The standard procedure for determining whether breast cancer has spread beyond the breast is a surgical technique called axillary lymph node dissection. Surgeons remove multiple lymph nodes from under the arm for pathological examination to determine if lymphatic fluid has carried any cancer cells beyond the breast tissue to the lymph nodes. This is vital information often used to determine the need for chemotherapy or hormone therapy. While the procedure has been key to determining the type and extent of therapy a breast cancer patient should receive, surgeons—including the Johns Hopkins Breast Center’s Julie Lange, M.D., assistant professor of surgery—are testing a new, less invasive procedure that might yield the same staging information in many patients. The procedure is called sentinel node biopsy.

The new procedure is based on the idea that cancer does not spread randomly but rather through very specific lymphatic channels. The first node or nodes to receive the lymphatic fluid is considered the sentinel node. If this sentinel node is free of cancer cells, it is likely that other nodes are free of disease as well.

This less invasive approach limits the disruption of tissues under the arm, so patients are less likely to suffer side effects such as numbness, pain, stiffness, and impaired shoulder mobility common to the traditional axillary lymph node dissection. In addition, detailed pathological examination of a single node, as opposed to a less thorough study of multiple nodes, could result in more detailed and accurate staging of the cancer.

Lange and her colleagues believe sentinel node biopsy is best suited for women with small, early stage tumors. She says, however, that while it may one day replace axillary dissection, it is still under clinical investigation. She points to a 10 percent false negative rate and lack of standardization in how the procedure is performed as areas of concern that must be addressed before sentinel node biopsy can be widely offered to patients.

New Research Highlight

Oncologists have long been plagued by the microscopic cancer cell that survives only to turn up months, even years later as a more difficult to manage recurrence of the disease.

Hopkins researchers are now investigating a combined treatment approach that may be able to stave off these cells. Known as immunotherapy, this experimental approach is initially being planned for study in women with advanced stages of breast cancer, where the disease has spread beyond the breast. Patients would first be treated with high doses of chemotherapy to kill as many cancer cells as possible, followed by an infusion of their own bone marrow, which replenishes vital blood and immune cells killed by the anticancer drugs. The final step is a breast cancer vaccine, administered by injection under the skin, which activates the immune system and causes it to seek out and kill remaining cancer cells anywhere in the body.

The vaccine approach, developed under the direction of Elizabeth Jaffee, M.D., associate professor of oncology, is genetically engineered to recognize and target immune-triggering substances known as antigens, produced by normal and cancer cells containing a defective copy of the growth-promoting gene known as HER-2/neu. In essence, the vaccine is a molecular signal to the immune system that it should search for and destroy any cells containing this antigen. And since the antigen is produced by not only cancer cells, but also normal cells genetically predisposed to turn malignant, the vaccine also shows promise as a future breast cancer prevention strategy.

For now, Jaffee and her colleagues are continuing to test the vaccine in animal models and are developing plans for clinical trials in humans.