Clinical Research News
Studies Identify New Options for Breast Cancer
At NewYork-Presbyterian Hospital/Columbia University Medical Center, the treatment of breast cancer involves a comprehensive approach that includes reducing toxicities as well as improving outcomes.
Initiatives designed to improve outcomes for patients with breast cancer are focused on an ambitious drug development program that often allows patients access to therapies not available outside of clinical trials, as well as an active prevention program that focuses on both drugs and nutrients with the potential to inhibit the mechanisms of malignant transformation.
Among the most important recent advances for the treatment of metastatic breast cancer is a drug called ixabepilone, which was approved in late 2007.
The drug is indicated for metastatic or locally advanced cancer resistant to taxane or anthracycline, and it can be combined with capecitabine or used as monotherapy.
It induces cell apoptosis by binding to tubulin and promoting tubulin polymerization and microtubule stabilization.
"It is a very effective drug in a population for which there have been limited options.
We have been working with this agent in the clinic for 6 years, so many of our patients were able to benefit from this agent before it was widely available," said Linda Vahdat, MD, lead investigator on the Phase III trial.
"I believe we have one of the most active clinical trials programs in breast cancer in the country, and several other drugs coming forward look promising."
One group of agents is called the epothilones, a new class of cytotoxic agents that have a mechanism similar to taxanes but are more soluble in water and have a dissimilar resistance profile.
A Weill Cornell research team led by Dr. Vahdat at NewYork-Presbyterian Hospital will serve as principal investigators in a registration trial of epithelone (ZK-Epo) that is now beginning to accrue patients.
"Our group published a paper in the Journal of Clinical Oncology a few months ago that evaluated joint symptoms in postmenopausal women taking adjuvant aromatase inhibitors," said Dawn L. Hershman, MD, MS.
"It demonstrated that 47% of patients on one of these agents had joint pain, which is more than previously reported.
When we conducted a multiple logistic regression analysis to identify risk factors, prior exposure to taxanes increased the risk of joint pain 4-fold.
Understanding the risks as well as the benefits of breast cancer therapy is the first step toward improving compliance with therapy.
With more women surviving breast cancer and living longer, active lives, it is essential that we understand and try to avoid complications that will diminish the quality of that life."
In both the treatment of early-stage breast cancer and in cancer prevention, several novel agents show promise, but one of the challenges is the difficulty of confirming efficacy of these agents.
Trials often require several thousand women and include 5 to 10 years of follow-up, which can be prohibitively expensive.
Katherine Crew, MD, MS, reported that one of her areas of investigation is identifying intermediate markers that might be surrogates of clinical benefit.
"One example is breast density," she said.
"Having dense breasts on a mammogram is a strong predictor of cancer risk.
So this may be a useful marker in intervention trials to test novel agents for breast cancer prevention.
Other markers we can look at include the rates of cell proliferation and apoptosis within the breast tissue."
She added that some of their initiatives involve novel chemopreventive agents, such as high-dose vitamin D and the use of green tea extract, a study that is being supported by the National Cancer Institute.
"We are now moving into an area where we can individualize therapy based on the molecular genetics of each patient's cancer and target therapies to patients in a more sophisticated and rational way," added Dr. Hershman.
"The Columbia clinical and basic science translational research teams at Herbert Irving Comprehensive Cancer Center at NewYork-Presbyterian/Columbia work hand-in-hand to exploit the findings from the large cadre of outstanding laboratory researchers.
We use these findings to design novel therapeutic trials that we can offer our patients, and move the field forward for all women."
Another major interest of Dr. Vahdat involves the use of a copper-depletion compound, called tetrathiomolybdate, to prevent angiogenesis; a trial is under way in women with breast cancer at high risk for relapse who have completed standard therapy but are looking for additional strategies that might help reduce the risk for tumors returning.
"We do not know what reignites malignant growth, but we do know that tumors cannot grow without a blood supply," she said.
"In a breast cancer animal model, copper depletion was highly effective in preventing metastases from forming.
What was interesting in these studies was that when copper was restored, the growth of metastases began almost immediately."
| 
