Update On American Society of Clinical Oncology(ASCO) Meeting  

The last meeting of the American Society of Clinical Oncology (ASCO) was unique in the fact that seminal studies in the area of prevention, early stage and advanced breast cancer were presented that may soon affect standard clinical care.

The results of two prevention studies were presented. One was designed to prevent breast cancer using the drug tamoxifen. It has been known for some time that using the drug in adjuvant studies, one could lower the risk of recurrence. Women given the drug were also noted to have fewer new breast cancers in the other breast. Tamoxifen almost cut in half these new cancers. This led to the design of a large trial for women at higher risk. In 1992 the trial was open to any woman between the ages of 45 and 70 as long as they met the risk criteria (risk of cancer equal to 60 year old woman, family history of breast cancer, etc.). The women were assigned either to tamoxifen or placebo for 5 years. After 4 years they analyzed the data, and found that the incidence of cancer in the treated half was about half that of the control group. Of the 13,000 women studied, 150 cancers were found in the control group and about 80 in the group receiving therapy. Preinvasive cancers were also reduced in the treatment group, as were the number of fractures found. The negative findings included increased numbers of uterine cancer and increased blood clots in the tamoxifen group. Those women who developed new cancers tended to be ER(-). Because the trial was stopped early, we may never really know whether we have increased survival statistics. This is one criticism of stopping the trial early and is certainly an issue to be considered. Once a treatment is found to be valid do you let the community know or continue with the trial?

Another area of prevention being studied is a drug called roloxafene, a small chemical refinement of tamoxifen makes it stimulate the uterus less, and presumably will not increase the risk of uterine cancer. This drug also reduces the risk of osteoporosis. The study was designed to look at rates of osteoporosis in women over the age of 65 with low BMD (bone mineral density). 10,000 women were enrolled and followed over a 10 year period in a drug vs. placebo trial. Preliminary results indicate a 70% reduction in the odds of getting breast cancer for the treatment group. Those cancers were also a higher proportion of ER(-). Studies must be done with early stage breast cancer in order to see if roloxafene can be substituted for tamoxifen, but these large studies take time. Negative side effects, such as memory loss, hot flashes, etc. still remain the same for both drugs, but a reduction in uterine cancer was seenwith roloxafene. Tamoxifen also cuts metastatic recurrence by 45%, so there would be a reluctance to move to a drug that hasn't yet been tested and may never be tested, due to high costs of testing.

The results of two large studies were presented in the area of adjuvant therapy, treatment following surgery in early stage breast cancer. One group of patients with negative nodes was treated with chemotherapy CMF or CAF with and without tamoxifen. The group with tamoxifen did a few percentage points better, and the CAF group actually did 1% better than CMF. The study was large enough to make this a significant difference. The other study investigated the addition of taxol to adriamycin and cytoxin. It compared patients with positive nodes with AC and then AC plus taxol. Various doses of adriamycin made no difference, but the addition of taxol made a 4% difference in recurrence risk. There was no effect on cardiac toxicity with taxol, but when all patients were checked, 6% of patients in all arms had some cardiac problems. Cardiac toxicity with adriamycin may be underestimated.

Two large HER2/neu studies were big news. In the antibody alone study, 222 women who had received 2 or more chemotherapies for advanced cancer received herceptin: 15% had shrinkage of their tumors, and time to progression was about 9 months. Positive effect is defined as 50% shrinkage of tumor held for at least 4 weeks. The chemo plus antibody study showed a strongly positive effect. Those patients given AC with and without the antibody had a longer time to progression and a better response rate. Herceptin clearly adds some benefits to patients whose tumors overexpress HER2/neu.