Predicting Chemo Response

Triple negative breast cancer markers predict chemo response

(RxWiki News) One of the mysteries of cancer is its unpredictability. Sometimes chemotherapies work, and sometimes they don't. Recent research may help physicians personalize treatment for individual patients.

Researchers have identified a genetic marker that can forecast which triple-negative breast cancers and some ovarian cancers can likely be treated with common platinum-based chemotherapy drugs.

Triple-negative breast cancer is among the most aggressive, because its cells have no receptors for estrogen, progesterone or the HER2 gene that can be blocked with hormonal or targeted therapies. About 20 percent of breast cancers are triple-negative.

"Ask your oncologist about the type of tumor testing available to you."

These findings from Brigham and Women's Hospital and Dana-Farber Cancer Institute scientists and colleagues could potentially lay the groundwork for developing a test that would pinpoint patients who could be treated most effectively with a single drug.

Commonly, cancer treatments damage the DNA inside tumor cells. When this happens, cancer becomes unable to grow. Some cancer cells can repair the DNA damage, but not all. The cells that can't fix their own DNA are the ones that die.

Andrea Richardson, M.D., Ph.D., co senior author of the study and surgical pathologist at Brigham and Women's and Dana-Farber, told dailyRx in an email, "This research represents the first steps to our being able to predict which breast and ovarian cancer patients will benefit from drugs that target defects in DNA repair."

The newly identified marker highlights breast and ovarian cancer cells that can't repair damage caused by platinum chemotherapy agents such as cisplatin and caboplatin.

Having a test that could pick up this marker would help treat triple-negative breast cancers that don't respond to current therapies.

"We currently do not have any targeted therapies for patients with triple-negative breast cancer, so if these laboratory findings are confirmed and an assay is created to predict sensitivity to drugs that target defective DNA repair, it would be a major step forward," says Dr. Richardson.

The marker was discovered by examining tissue samples from women with triple-negative breast cancer who were participating in two clinical trials to test a platinum drug therapy.

During these trials, 79 patients received either cisplatin alone or in combination with bevacizumab (Avastin). The goal was to shrink tumors before surgically removing them.

About 40 percent of patients had total or nearly complete disappearance of tumors follow cisplatin therapies.

Analyzing the tissue of patients who responded to the therapies before and after treatment, researchers found loss of chromosomes in the tumor cells and were able to identify a pattern, or genetic marker.

The next step will be to develop a test (assay) that can pinpoint these markers, something that's not likely to happen anytime soon, according to Dr. Richardson.

"When/if such a predictive assay becomes available, this will help us to tailor therapy for individual patients to improve outcomes and reduce unnecessary toxicity," she wrote to dailyRx in an email.

A report on these studies is being published in the April issue of Cancer Discovery.

Grants from the National Cancer Institute and several foundations supported this research.

A pending patent application is based on these findings.  The patent through Dana Farber Cancer Institute, Children's Hospital of Boston, and Brigham and Women's Hospital lists Dr. Richardson and several of the co-authors as inventors.

Review Date: 
March 21, 2012