Dr Dennis Slamon gets prestigious award

[al from Canada]

Dr. Slamon Presented with 2006 Karnofsky Memorial Award

Dennis J. Slamon, MD, PhD, a leading expert in the molecular pathogenesis of cancer, is the 2006 recipient of the David A. Karnofsky Memorial Award. Dr. Slamon’s pioneering research has resulted in a new approach to treating patients with breast cancer by specifically targeting the defective genes that lead to its development.

“This is an incredible honor that I must receive on behalf of my colleagues [and] UCLA, which provides an incredible environment supporting and encouraging research,” said Dr. Slamon. “I must also acknowledge study patients who are our full partners in translational research.” He delivered his Karnofsky Memorial Lecture, “Molecular Diversity of Human Breast Cancer: Therapeutic Implications,” after the Presidential Address on Saturday afternoon.

Traditional descriptive approaches to cancer treatment, he noted, have not been effective in treating many malignancies. Dr. Slamon and his colleagues at UCLA developed the monoclonal antibody trastuzumab, the first targeted treatment of HER-2-positive breast cancer.

Trastuzumab’s story begins with the identification of gene overexpression. Patients with breast cancer whose disease overexpresses HER-2 had shorter survival rates than did those with normal levels of HER-2. Dr. Slamon and his colleagues developed a monoclonal antibody targeting overexpressing HER-2 carcinoma cells, and phase I trials found that single-dose trastuzumab was effective as monotherapy. Phase III trials of trastuzumab plus chemotherapy compared with chemotherapy alone demonstrated a 53% increase in relative response and a 58% increase in duration of response. Additionally, investigators found trastuzumab to be well tolerated. At 1-year of follow-up, the survival rate for patients receiving trastuzumab plus chemotherapy survival rate was 78% compared with 67% for those receiving chemotherapy alone.

Trastuzumab, although well tolerated, increases the incidence of adverse cardiac events, particularly when used with anthracycline-based therapy. Dr. Slamon noted that a prospective analysis to determine ways to reduce cardiac risk is underway.

Clinicians now understand that each cancer has a different underlying molecular genetic structure, says Dr. Slamon. Six to eight categories of breast cancer have been identified, each one behaving differently, and as such, he believes that treatments tailored to each type of cancer need to be developed. Lapatinib — another HER-2 inhibitor — is being studied in combination with chemotherapy and trastuzumab. Dr. Slamon noted that investigators have observed promising results, although studies are ongoing. Dr. Slamon believes that attacking cancer at its genetic roots holds the most promise for developing new, more efficacious targeted treatments with minimum toxicity and maximum efficacy.

The therapeutic applications of trastuzumab, he believes, have expanded. Recent clinical trials have shown a dramatic reduction in recurrence rates for those with early stage breast cancer who receive trastuzumab in addition to surgery and chemotherapy.

Dr. Slamon noted that research remains one of his top priorities. He is now investigating the effectiveness of trastuzumab in newly diagnosed patients with breast cancer and is investigating new treatments for women with both breast and ovarian cancers. Dr. Slamon hopes to identify additional targets that have the potential to reduce the number of women who die from breast cancer.

Although the development of trastuzumab and other targeted therapies has revolutionized the way patients with cancer are treated, the real heroines of the trastuzumab story are the group of 20 women who enrolled in the first trastuzumab clinical trial in 1992.