San Antonio Breast Cancer Symposium Update, 1998

Several important advances were covered at the San Antonio Breast Cancer Symposium held in December of 1998. In the area of Breast cancer prevention, findings from the NSABP P01 Prevention Trial now confirm that in the short term, over about 5 years, patients taking tamoxifen who are at higher than average risk for getting breast cancer can reduce their risk of actually getting breast cancer by one-half.

Based on this information, the Food and Drug Administration has approved tamoxifen as a drug that can lower the short term incidence of breast cancer. It is important to recognize that tamoxifen may not actually be preventing cancer since in the opinion of most scientists, the development of breast cancer takes as many as 5 to 15 years to develop. Therefore, it is likely that what tamoxifen is doing is actually treating established breast cancers that are microscopic and undetectable. This leaves in question what the long-term effects of tamixofen prevention might be and the best time for a woman to take this if she is at higher risk.

Data from other clinical trials as well as from laboratory models suggest that the year-to year risk of getting breast cancer may actually be lower even after one has stopped taking tamoxifen. In the prevention trials, there was a higher risk of uterine cancer, blood clots, and the development of cataracts, especially in women over age 50. Even though tamixofen can now be prescribed as a "prevention" agent, it remains unclear in which population of women the benefits in terms of lowering the risk of a new cancer will actually outweigh some of the risks associated with tamoxifen. Furthermore, tamoxifen only seems to prevent ER+ breast cancers and this also brings into question whether or not the cancers that develop if one is on tamoxifen as a preventive agent might be more aggressive. Due to this question, it then remains unclear whether or not we are actually saving lives by using tamoxifen as a preventive agent. Hopefully these questions will be answered from other trials in which mortality is being looked at. There is also a trial planned to compare tamoxifen to raloxifene as a preventive agent for breast cancer. Raloxifene has the advantage that it may not increase the risk of uterine cancer.

Other findings included further information on the use of HER2/neu as a marker to identify who might benefit from different types of hormonal or chemotherapy for early stage breast cancer. Information from both the NASBP as well as from the Intergroup (two large American collaborative cancer clinical trial groups) show that in different trials looking at the chemotherapy Adriamycin, that patients whose tumors overexpressed HER2/neu (made high amounts of the protein encoded by the HER2/neu gene) seem to benefit more from Adriamycin. In older women, a study looking at tamoxifen alone compared to tamoxifen with an Adriamycin-containing chemotherapy regimen suggested that only among patients whose tumors overexpressed HER2/neu was there an actual benefit from chemotherapy. In women whose tumors were HER2/neu-negative, equal results were obtained with tamoxifen compared to tamoxifen plus chemotherapy. Finally, updated information from the clinical trials using HER2/neu humanized monoclonal antibody (Herceptin) were presented.

The updated results of a trial in which women received Herceptin as the only treatment if they had a metastatic breast cancer which over expressed HER2/neu and had progressed after one or two chemotherapy regimens was presented. 14% of women in this trial that included 222 women had a response to Herceptin. The average response time was about nine months. It still remains unclear why a majority of women do not respond to Herceptin, but certainly for those that do respond, there is a clinical benefit associated with it. Another trial compared chemotherapy alone to chemotherapy with Herceptin also for women with metastatic, HER2/neu-positive breast cancer.

This study showed convincingly that the addition of Herceptin improved the effectiveness of chemotherapy. The average time after which patients had progression of their tumor was significantly prolonged. The number of patients who had a response in the first place was also improved and the one-year survival was improved. Again, these changes were not as dramatic as one would like to see, but clearly demonstrate the biological effectiveness of Herceptin at least in some women.