Results: Phase I/II Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients With Locally Advanced or Metastatic Breast Cancer

Dr. Linda Vahdat and her colleagues are very excited to be involved in the development of glembatumuma vedotin as it has the potential to be among the very first drugs for triple negative breast cancer.

http://jco.ascopubs.org/content/early/2014/09/29/JCO.2013.52.5683.full.pdf+html

Weill Cornell Researchers: Copper Depletion Therapy Keeps High-Risk Triple-Negative Breast Cancer at Bay

Researchers at Weill Cornell Medical College have recently published the results of a Phase II clinical trial conducted at the Weill Cornell Breast Center. The results show that an anti-copper drug called tetrathiomolybdate (TM) that disables the ability of bone marrow cells from setting up a “home” in organs to receive and nurture migrating cancer tumor cells has shown surprising benefit in treating high-risk triple-negative breast cancer, one of the most difficult-to-treat forms of cancer.

The median survival for metastatic triple-negative breast cancer patients is historically nine months. However, the results of the study, recently published in the Annals of Oncology, show that if patients at high-risk of relapse with no current visible breast cancer are copper depleted, it results in a prolonged period of time with no cancer recurrence. Only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after treatment with tetrathiomolybdate (TM).

“These study findings are very promising and potentially a very exciting advance in our efforts to help women who are at the highest risk of recurrence,” says the study’s senior investigator, Dr. Linda Vahdat, director of the Breast Cancer Research Program, chief of the Solid Tumor Service and Professor of Medicine at Weill Cornell Medical College.

Four of the study participants with a history of metastatic triple-negative breast cancer have had long-term benefit remaining disease free for between three and five and a half years.

“The anti-copper compound appears to be keeping tumors that want to spread in a dormant state,” reports Dr. Vahdat. “We believe one of the important ways it works is by affecting the tumor microenvironment, specifically the bone marrow-derived cells that are critical for metastasis progression.”

In addition, study participants with other forms of high-risk for relapse breast cancers — either stage 3 or stage 4 — without evidence of disease after treatment have also fared well. The progression-free survival rate among these 29 patients in the study has been 85 percent, to date.

“As good as these interim findings look to us, we cannot talk about significant benefit until we compare TM treatment to other therapies,” she says. Dr. Vahdat expects to launch a phase III randomized clinical trial in the near future.

This research is a report of the first 40 patients. The clinical trial, which began in 2007, has been expanded many times and now includes 60 patients, more than half of who have triple-negative breast cancer.

Click here to read the Weill Cornell press release. Click here to read the published research paper.

Cornell University Researchers Discover Switch That Controls Spread of Breast Cancer

Cancer has long been associated with inflammation. Biomedical engineers at Cornell University have now found the natural “switch” between the body’s response to inflammation and breast cancer metastasis–how malignant breast cancer cells use the bloodstream to spread elsewhere in the body.¬† The findings were recently published in the scientific journal PLOS ONE.

Cancer cells spread by sticking to the the thin lining of blood vessels, called the endothelium. However, it has been unclear how the cancer cells manage to do this. Researchers in the lab of Michael R. King, professor of biomedical engineering at Cornell, developed a flow chamber that resembles the lining of endothelium in order to determine  how breast cancer cells spread through blood and attach to cells.

In analyzing hormone therapy-resistant breast cancer cells sticking to the endothelium, the researchers accidentally discovered  that these cells interacted with receptor sites in blood vessels known as selectins. The is is a similar process as white blood cells racing to blood vessels to fight infection and inflammation.

The researchers found that the presence of pro-inflammatory molecules called cytokines helped the malignant breast cancer cells adhere to the endothelial wall, thus leading to metastasis. The cytokines then help promote growth of breast cancer cells, triggering other cells to release more cytokines.

The researchers then treated the cells with an anti-inflammatory drug called Metformin, used to treat diabetes. After treatment with Metformin, the cells were not able to metastasize, thus confirming the findings.

The authors write, “There is compelling evidence supporting the strong interplay between various types of inflammation and cancer progression suggested by numerous clinical and epidemiological studies….Taken together, these results suggest that therapeutic approaches targeting cytokine receptors and adhesion molecules on cancer cells may help reduce the likelihood of metastasis and deserve further attention.”

Click here to read the published research study.

Weill Cornell Researchers: Triple Negative Breast Cancer Metastasis Can Be Halted, Potential New Therapies on Horizon

Researchers at Weill Cornell Medical College have discovered the molecular switch that allows aggressive triple negative breast cancer cells to grow the amoeba-like protrusions they need to move away from a primary tumor and metastasize throughout the body. These findings, published today in Cancer Cell, suggest a novel approach for developing therapies to treat cancer once it has metastasized.

The researchers discovered that a miRNA (a small, non-coding RNA that regulates gene expression) called miR-708 is inhibited in metastatic triple negative breast cancer. miR708 acts as a metastatic tumor inhibitor, and when its function is restored, the tumors do not spread or form lethal macrometastases.

Triple negative breast cancer was chosen for the examination of the role of miRNAs because it has the worst outcome of all breast cancer subtypes due to its high recurrence rate and metastatic spread.

The researchers found that delivering synthetic miR-708 blocked metastatic outgrowth of triple negative breast cancer cells in the lung of mice. That makes miR-708 a promising therapeutic against metastatic breast cancer. Dr. Vivek Mittal, director of the Lehman Brothers Lung Cancer Laboratory at Weill Cornell Medical College and the study’s senior investigator, said that the findings suggest that agents now being tested for lymphoma cancer cells may also help restore miR-708 in triple negative breast cancer.

Dr. Linda Vahdat, director of the Weill Cornell Breast Cancer Research Program, Chief of the Solid Tumor Service and a co-investigator on the study said, “These study results are terrific. It not only offers us an avenue to treat metastatic triple negative breast cancer in the short-term, but also gives us the road map to prevent metastases in the long-run. We are anxious to get this into the clinic, and we are working as quickly as possible towards that end.”

Click here to read the full press release. Click here to read the published research paper.