Harold Burstein, MD, PhD, assistant professor of medicine, Dana-Farber Cancer Institute/Harvard School of Medicine, Boston, Massachusetts, United States, presented the history of how monoclonal antibodies have changed the nature of treatment for breast cancer and its implication for future treatment.

"We first identified that there were important subsets of breast cancers that were defined by molecular markers," Dr. Burstein explained in his presentation on April 13^th. "After identifying the molecular markers, we began to ask the question: 'Which women might be able to skip chemotherapy altogether?'"

Subsequent research has shown that 65% to 75% of all breast cancers are oestrogen-receptor positive. Within this subset, 15% to 20% of all breast tumours overexpress the human epidermal growth factor receptor 2 (HER2) gene and, therefore, are susceptible to trastuzumab therapy. The use of trastuzumab, a monoclonal antibody, has also been explored in the adjuvant setting through several large trials, such as the National Surgical Adjuvant Breast Project B-31 trial.

There has been some concern about the cardiac risks associated with trastuzumab therapy. However, said Dr. Burstein, "For most women, the cardiac risks are small compared to the benefits." The risk has been quantified between 1% and 3%, he said.

Dr. Burstein noted other key issues remain with respect to trastuzumab therapy, such as: the timing of trastuzumab administration in relation to traditional chemotherapy; the optimal chemotherapy backbone; and ideal patient selection criteria for lower-risk, node-negative disease. "What remains to be determined is the optimal duration of trastuzumab treatment as well as an optimal cardiac monitoring strategy," he said.

Also on the horizon is the use of lapatinib, a small molecule, which has shown to disrupt the HER2 receptor. There are trials underway in which lapatinib is administered in combination with trastuzumab in the neoadjuvant setting.

In explaining the issue of adjuvant endocrine therapy, Dr. Burstein commented on the use of tamoxifen and aromatase inhibitors. He cited recent studies with a combination of tamoxifen and aromatase inhibitor, but the optimal sequencing and duration of such therapy is yet to be determined. In addition, better management of the osteoporosis and other risks associated with aromatase inhibitor therapy is required, he said.

"While we can do better than 5 years of tamoxifen therapy," he said, "the optimal duration of aromatase inhibitor therapy is unknown."


[Presentation title: Clinical Trials Update: Adjuvant Trastuzumab, Adjuvant Endocrine Therapy.]

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