Breast cancer continues to be a dynamic field of research, and the CTRC-AACR San Antonio Breast Cancer Symposium, now in its 32nd year, is the premier destination to present new data on emerging therapies.
C. Kent Osborne, M.D., director of the Dan L. Duncan Cancer Center and the Lester and Sue Smith Breast Center at Baylor College of Medicine and president of the symposium, will host a Drugs in the Pipeline press conference on Friday, Dec. 11, at 8:00 a.m. CT, in room 217C of the Henry B. Gonzales Convention Center.
Reporters who cannot attend in person may participate by using the following information:
•U.S. & Canada: (888) 282-7404
•International: (706) 679-5207
•Access Code: 39118522
•Topic: AACR
The following abstracts will be presented at the press conference:
48. Targeting Intrinsically-Resistant Breast Cancer Stem Cells with Gamma-Secretase Inhibitors
Treating breast cancer with a "Notch" pathway inhibitor reduced the ability of cancer stem cells to replenish themselves and promote tumor growth, researchers reported at the CTRC-AACR San Antonio Breast Cancer Symposium. These findings suggest that ongoing clinical trials testing this class of agents could offer promising results, especially when combined with other anticancer treatments.
"The Notch pathway regulates self-renewal of stem cells and our research indicates that it also regulates cancer stem cell self-renewal," said the study's lead author, Jenny Chang, M.D., professor of medicine at Baylor College of Medicine.
The impact of using a Notch inhibitor, she said, was to sensitize a significant proportion of otherwise treatment-resistant cancer stem cells, and this supports the notion that a select subpopulation of cells in breast cancer is largely responsible for disease recurrence and cancer spread.
Researchers from Baylor College of Medicine, University of Michigan and Dana-Farber Cancer Institute focused on "mammosphere-forming" human breast cancer cells — cells that have been found to have stem cell properties and are resistant to conventional chemotherapy. These cancer cells can be identified because of their protein signature; they express high levels of CD44, a protein involved in migration, and low or undetectable levels of the cell adhesion protein CD24. Gene analysis of these cells showed that a number of pathways are activated, such as Notch, PI3K and Hedgehog, compared to non-cancerous cells.
In this study, researchers tested gamma-secretase inhibitors in preclinical cancer stem cell models and a complementary clinical trial of a gamma-secretase inhibitor in breast cancer patients. Gamma-secretase is required for activation of the Notch signaling pathway, which regulates self-renewal of stem cells.
The research team implanted human triple-negative breast cancer obtained from patients in two independent sets of mice, and then treated them with a gamma-secretase inhibitor. They isolated the tumors in the mice and found that mammosphere formation was impaired, but tumor volume was not affected.
"Because the cancer stem cell population may be a very small percentage of the tumor cells (0.1 percent to 1 percent), tumor volume measurement is not sensitive enough to measure effects on the cancer stem cell population," Chang said.
Researchers then studied tumor biopsies taken from a patient with metastatic breast cancer enrolled in a complementary clinical trial of a gamma-secretase inhibitor conducted at Baylor College of Medicine. They looked at biopsies before and during treatment. Findings showed that mammosphere-forming efficiency declined after the first cycle of the agent combined with chemotherapy, and tumor response was seen only after several rounds of therapy.
"The agent reduced the tumorigenic cancer cells," Chang said. "To eliminate these cells, combination therapy that targets additional pathways regulating cancer stem cells will be essential."
25. CONFIRM: A Phase III, Randomized, Parallel-Group Trial Comparing Fulvestrant 250 mg vs Fulvestrant 500 mg in Postmenopausal Women with Estrogen Receptor-Positive Advanced Breast Cancer
Embargoed until 4:00 p.m. CT, Dec. 10, 2009
A higher dose of fulvestrant is well tolerated and more active than the standard, lower dose in postmenopausal patients with advanced breast cancer.
"We believe that, based on the results of this study, treatment and practice should change; patients should receive the 500 mg dose," said Angelo Di Leo, M.D., Ph.D., director of the Department of Oncology at the Hospital of Prato, Italy.
Fulvestrant, sold under the trade name Faslodex by AstraZeneca, is an estrogen receptor antagonist used for the treatment of metastatic receptor-positive breast cancer in women who have progressed or had recurrent cancer after prior endocrine therapy.
Di Leo and colleagues conducted the CONFIRM study — Comparison of Faslodex In Recurrent or Metastatic breast cancer — to compare the efficacy, response rate, clinical benefit, duration of benefit and response, quality of life and overall survival of the drug at the standard 250 mg per month dose and 500 mg per month dose. Over a two-year period, the researchers recruited 736 women from 128 centers located in 17 countries to participate in this study.
Findings showed that the 500 mg dose of fulvestrant was more active and as well tolerated as the 250 mg dose of fulvestrant, according to Di Leo, who will present further results of this randomized, phase III trial at the CTRC-AACR Annual San Antonio Breast Cancer Symposium, to be held Dec. 9-13, 2009.
The researchers are currently conducting the Trans-CONFIRM study in an effort to understand if the higher dose is mandatory in all patients, or only some.
44. A Double-Blind, Randomized, Placebo-Controlled, Phase 2b Study Evaluating the Efficacy and Safety of Sorafenib in Combination with Paclitaxel as a First-Line Therapy in Patients with Locally Recurrent or Metastatic Breast Cancer
Combining chemotherapy with a drug widely used to treat liver and kidney cancer has offered advanced breast cancer patients with HER2-negative tumors significant improvement in overall response rate and time-to-disease progression, according to new results from an international trial presented at the CTRC-AACR San Antonio Breast Cancer Symposium.
The combination of sorafenib and paclitaxel also demonstrated a favorable trend in progression-free survival, according to lead investigator William Gradishar, M.D., professor of medicine at the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. Data on overall survival are not yet available.
"These data indicate that sorafenib provides added benefit when combined with paclitaxel compared to single agent paclitaxel in the first-line treatment of advanced breast cancer," Gradishar said.
The study, a double-blind, randomized, placebo-controlled phase IIb study, was conducted in the United States (95 patients), India (170 patients) and Brazil (15 patients). It is the second in a series of four worldwide stage IIb clinical trials testing the use of sorafenib in recurrent or metastatic HER2-negative breast cancer in a program called TIES (Trials to Investigate the Effects of Sorafenib in breast cancer).