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Researchers Link CEP17 Breast Cancer Tumors to Anthracycline Response

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Originally published March 29.

By Turna Ray

Breast cancer patients with a mutation on chromosome 17 are more likely to see better outcomes from anthracycline treatment than those without the mutation, researchers reported during the European Breast Cancer Conference this week in Barcelona, Spain.

In the study, researchers led by John Bartlett, professor of molecular pathology at the University of Edinburgh, performed a retrospective meta-analysis of data from nearly 3,000 patients in four trials to test the hypothesis that duplication of chromosome 17 alpha satellite predicts sensitivity to anthracyclines.

The researchers found that patients with CEP17 tumors treated with anthracyclines, were approximately two-thirds more likely to survive without a recurrence of cancer than those who did not receive anthracyclines.

Fluorescent in situ hybridization testing of patient tumors was conducted at two laboratories. The study compared outcomes for four groups, patients with CEP17 tumors treated with anthracyclines, patients without CEP17 tumors treated with anthracyclines, patients with CEP17 tumors treated with non-anthracycline based chemo, and patients without CEP17 tumors treated with non-anthra-cycline based chemo.

Researchers were able to detect CEP17 duplication in 27.5 percent of tumors and found that that CEP17 status was also associated with poorer overall survival and recurrence-free survival. However, when this group of patients was analyzed for their response to anthracyclines, "a significant treatment by marker interaction was observed," the researchers noted in their abstract.

"What the study showed was that the addition of anthracyclines to patients with CEP17 tumors had improved survival," Bartlett told Pharmacogenomics Reporter this week. Around 67 percent of patients with CEP17 tumors treated with anthracyclines experienced recurrence-free survival, and overall survival in this group was 63 percent.

"CEP17 duplication may reflect either chromosomal instability or polyploidy and further analysis will explore the underlying mechanisms for this effect," the researchers concluded in their abstract.

According to Bartlett, this finding, pending further validation, suggests that only patients with CEP17 tumors should receive anthracyclines. This means that those who do not have this marker can avoid anthracycline-based chemotherapies, as well as treatment-related toxicities. Further research could also lead to new CEP17 pathway-targeting cancer drugs.

"The research … is important because, until now, there was conflicting evidence about the best way of predicting response to anthracyclines and it was unclear whether any of the known biomarkers, such as the genes HER2 and TOP2A, were accurate indicators of response to these drugs," the European Cancer Organisation said in a statement announcing the study.

CEP17 is on the same chromosome as two other genes known to be involved in breast cancer, HER2 and TOP2A. However, in previous investigations, researchers found conflicting evidence about associations between HER2 and TOP2A markers and anthracycline response.

“We need to understand what CEP17 is telling us about the behavior of breast cancer cells," Bartlett said in a statement "It works as a biomarker for predicting response to anthracyclines, but we don’t know why it works."

Anthracyclines, widely used cancer treatments, are anti-tumor antibiotics that interfere with enzymes in DNA replication. Some examples of commonly used of anthracyclines, according to the American Cancer Society, include daunorubicin, doxorubicin (Adriamycin), epirubicin, and idarubicin.

According to Bartlett, the next step is to try to figure out why CEP17 tumors behave has they do, "and to try to make the cancers that don’t have the marker behave like the ones that do, so that they will respond to anthracyclines," Bartlett added.

CEP17 is detected by FISH testing, which is routinely used to establish HER2 status for breast cancer patients. As such, Bartlett pointed out that establishing CEP17 status in cancer patients can be done as they are being tested to see if they will respond to Herceptin.

Bartlett's research team is planning follow-up studies to identify the mechanism at work in this finding and may also perform a clinical trial to select patients using this marker.

The research was funded by Cancer Research UK, among other sources.

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