New Investigations in Prevention, Detection, and Treatment

Selective estrogen receptor modulators (SERMs), such as tamoxifen and raloxifene: The first widely used SERM, tamoxifen, a breast cancer treatment for more than 20 years, was recently found to be an effective risk reduction agent for women with high risk of developing breast cancer, but had the serious side-effect of increased risk for endometrial cancer and blood clots. Raloxifene, a second-generation SERM, was shown to reduce the risk of breast cancer without increasing the risk of endometrial cancer in a recent clinical trial designed to evaluate its effect on osteoporosis in postmenopausal women. A new randomized clinical trial supported by the National Cancer Institute will directly compare the effectiveness of tamoxifen and raloxifene in reducing breast cancer incidence in postmenopausal women at high-risk for breast cancer.

Screening technologies

Although mammography is accepted as the imaging standard, other imaging techniques are being investigated, including computer-based or digital mammography, magnetic resonance imaging (MRI), and positron emission tomography (PET).

Chemotherapeutic agents

A host of chemotherapy drugs and drug combinations, which are believed to be more effective and less toxic than current regimens, are currently being evaluated.

High-dose chemotherapy with autologous bone marrow transplantation (ABMT): ABMT is designed to provide a "rescue" from severe chemotherapy-induced bone marrow suppression by reintroducing the patient's own bone marrow or stem cells from their blood, thereby allowing higher than normal doses of chemotherapy to be used. Recently, two large US studies reported preliminary results indicating that patients undergoing ABMT and receiving higher doses of chemotherapy did not experience any survival benefit after follow-up averaging three years compared to standard regimens. However, large-scale NCI-supported clinical trials currently underway will provide additional information to evaluate the effectiveness of this procedure.

Immunotherapy

In addition to recent and ongoing studies to determine the exact role of trastuzumab in breast cancer treatment, clinical trials are evaluating other monoclonal antibody therapies directed against the HER-2 protein and other breast cancer cell components. Some of these antibodies work by blocking growth-promoting molecules, others stimulate an immune reaction to the cancer, or target radioactive atoms to the cancer cells. Vaccine therapies are also being tested, to see if they can help a woman's immune system recognize and attack breast cancer cells more effectively.

Angiogenesis prevention

For tumors to be able to grow, new blood vessels must develop (angiogenesis) to nourish the cancer cells. The extent of angiogenesis is a predictor of aggressiveness and may be useful in predicting breast cancer patient outcomes. New anti-angiogenesis drugs, which may stop cancer growth and spread by preventing the formation of blood vessels, are under development and testing in clinical trials.

Source: American Cancer Society, Inc.

National Research Agenda

In 1998, the Breast Cancer Progress Review Group, a collaboration of prominent members of the scientific, medical, advocacy, and industry communities formed by the National Cancer Institute, released their recommendations for a national breast cancer research agenda. The report included research goals in biology, etiology, genetics, prevention, detection and diagnosis, treatment, control, and outcomes.

Among the goals in these eight areas are:

• to expand knowledge of normal breast development and the earliest breast lesions;
• to identify modifiable risk factors, and to investigate the interaction between genes and environment;
• to identify genetic mutations that occur at each stage of breast cancer development and progression, and evaluate these changes as targets for intervention;
• to identify surrogate endpoint biomarkers to serve as early indicators of intervention effectiveness;
• to develop better breast imaging and other technologies for diagnosis of clinically significant disease and better prediction of clinical outcomes;
• to encourage development of innovative treatments in academic settings, and to test their effectiveness through better supported, more representative clinical trials;
• to gain fuller understanding of mechanisms underlying behavioral change, and identify how psychosocial factors influence disease response and survival; and, to better understand the effects of multimodal treatments, and improve methods to study patient-focused outcomes across the continuum of age and race/ethnicity.