Built on preclinical studies at MD Anderson that showed mTOR inhibition makes mice with HER2-positive and PTEN-deficient breast tumors more sensitive to Herceptin, the study was part of MD Anderson's and Dana- Farber Cancer Institute's breast cancer SPORE (Specialized Program of Research Excellence) grant from the National Cancer Institute.
"This study is important to breast cancer treatment, and it represents a crucial step toward personalized cancer therapy by increasing our understanding of cancer pathways," said Francisco J. Esteva, M.D., Ph.D., professor in MD Anderson's Department of Breast Medical Oncology and corresponding author. "It's the culmination of more than five years, starting with basic research and animal studies, and an excellent example of bench-to-bedside research."
Approach Shows Promise
Presented in part at the 2010 annual meeting of the American Society of Clinical Oncology, the study stemmed from two concurrent trials at MD Anderson and Dana-Farber. Forty-seven women with HER2-positive metastatic breast cancer that had progressed on Herceptin-based therapy were given Herceptin every three weeks and Afinitor daily. Almost half the women had previously received two or more chemotherapy regimens.
The combination therapy resulted in partial responses in 15 percent of patients and persistent stable disease in 19 percent of patients, resulting in a clinical benefit rate of 34 percent. Median progression-free survival was four months. Treatment was well tolerated, and side effects, which included fatigue, infection and mouth sores, were manageable.
Patients with PTEN loss had lower rates of overall survival, but progression-free survival was not affected, suggesting that PTEN loss enables activation of pathways that promote cancer growth. However, PIK3 mutations did not significantly affect progression-free survival or overall survival. The finding that progression-free survival was not s
|Contact: Laura Sussman|
University of Texas M. D. Anderson Cancer Center