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Researchers Have Identified Subgroup Sensitive to the Drug Cisplatin

Researchers have identified a subgroup of hard-to-treat breast cancers that may be sensitive to the drug cisplatin, rarely used in the treatment of breast tumors. They also have discovered// the molecular basis of this sensitivity, which may help identify patients most likely to benefit from cisplatin treatment. The findings will be tested in a clinical trial anticipated to begin at the MGH Gillette Center for Breast Cancer and collaborating institutions later this spring.

"This paper describes a specific molecular pathway that makes these tumors sensitive to a therapy infrequently used for breast cancer," says Leif Ellisen, MD, PhD, of the MGH Cancer Center, senior author of the study to appear in the May 2007 Journal of Clinical Investigation and receiving early online release. "We’re excited that this work has led to the design of a clinical trial for women with a very difficult to treat form of breast cancer."

About two thirds of breast cancers contain receptor molecules for the hormones estrogen or progesterone, and in recent years antiestrogen drugs like tamoxifen have improved outcomes for women with those tumors. About 20 to 30 percent of tumors, some with hormone receptors, have elevated levels of a growth-promoting protein called HER2, and those tumors are candidates for treatment with the monoclonal antibody Herceptin. The third major subtype is the 15 to 20 percent of breast tumors that have neither estrogen nor progesterone receptors and also do not overexpress HER2.

Since these so-called "triple-negative" tumors are treatable with neither Herceptin nor antiestrogen drugs, the prognosis for patients with the tumors has been poor. Triple-negative tumors are the most common subtype found in patients with mutations in the BRCA1 gene, but they also appear in women without alterations in the so-called "breast cancer gene." There have been reports that BRCA1-associated, triple-negative tumors might be sensitive to cisplat
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