Barcelona—A meta-analysis of 4 large breast cancer trials reveals that a particular chromosome abnormality is a highly significant indicator that a patient’s breast cancer will respond to anthracycline therapy, announced an international team of researchers at the EBCC7 meeting.
According to the lead author on the current study, John Bartlett, PhD, professor of molecular pathology at the University of Edinburgh, United Kingdom, evidence on whether the HER2 and TOP2A genes could provide accurate indication of tumor response to anthracyclines is conflicting. Earlier research by Dr Bartlett did show that duplication of chromosome 17 alpha satellite (CEP17) predicted sensitivity to anthracyclines. The present retrospective meta-analysis of nearly 3000 patients attempted to sort out this conflicting evidence.
The test used to assess patient genetic sequences, fluorescent in situ hybridization or FISH, is carried out routinely in breast cancer patients; it is used to test for the HER2 gene to see whether the woman might benefit from the drug trastuzumab (Herceptin). Because CEP17 is on the same chromosome as the HER2 and TOP2A genes, the assessment for CEP17 could be easily carried out in the same FISH analysis as for HER2, said Dr Bartlett. In the present study, Dr Bartlett’s lab conducted the FISH analysis on samples from the original trials.
Overall, CEP17 duplication was detected in 27.5% of tumors and was associated with poorer overall survival (OS) and recurrence-free survival (RFS). Patients with this genetic abnormality who were treated with anthracyclines were approximately two-thirds more likely to survive (OS = 63%) and to survive without a recurrence of cancer (RFS = 67%) than those who did not receive anthracyclines.
In a press release announcing the findings, Dr Bartlett stated that “our finding that patients whose tumors have the CEP17 abnormality are more likely to respond to anthracyclines is entirely novel.” This genetic abnormality, the authors conclude, may represent a clinically useful biomarker for selection of patients likely to benefit from anthracycline-containing chemotherapies.
In addition to helping better target chemotherapy, the discovery may open the way for biochemists to research the mechanisms involved in CEP17 and to design new drugs to target these pathways.
He cautioned that these findings need to be validated, saying “whilst the finding is of high evidence level, we need to confirm its applicability in an era where taxanes are a key component of treatment choice.” Never theless, they suggest that “only those patients with CEP17 tumors should receive anthracyclines, thereby en abling other patients who do not have the CEP17 abnormality to avoid a toxic treatment that will not be effective.”
