Genetic markers predict residual tumor response to adjuvant chemotherapy

NEW YORK (Reuters Health) - A gene-expression profile associated with resistance to induced DNA damage can help identify cancer patients likely to benefit from adjuvant therapy after surgical excision of the primary tumor, according to a report in the November 10 early online edition of the Proceedings of the National Academy of Sciences.

Researchers in the US and Europe previously identified the "interferon-related DNA damage resistance signature (IRDS)," which involved 49 genes.

"Cells that are IRDS(+) show constitutive activation of the STAT1/IFN pathway," principal investigator Dr. Andy J. Minn at the University of Chicago and his associates explain, and this results in pro-survival signals.

Using a murine xenograft model of human squamous cell carcinoma, they demonstrated that "IRDS genes primarily regulate ... resistance to DNA damage but not metastasis."

They examined IRDS expression in multiple patient samples from a variety of different cancers (breast, head and neck, prostate, lung, and glioma). Roughly one third to one half of cases could be classified as IRDS(+).

In a group of 78 breast cancer cases, Dr. Minn's group identified the 7 genes most highly associated with IRDS status. When they analyzed clinical outcome in 295 patients with early-stage breast cancer, they observed that this 7-gene expression profile predicted outcome only among patients treated with adjunctive chemotherapy.

"The IRDS can be integrated with available prognostic tools to identify patients at risk for distant relapse who can be rendered at low risk by adjunctive chemotherapy," the authors report. IRDS also predicted local-regional control after radiation therapy.

The team independently validated the IRDS as a therapy-predictive marker in four large independent breast cancer data sets involving a merged set of 1573 patients.

Dr. Minn's team suggests that knowledge of a patient's IRDS status can assist in the decision to administer adjunctive therapy.

"Conversely," they add, "knowledge that (conventional) chemotherapy will be ineffective may compel patients to accept more aggressive therapies," such as anthracycline and taxane treatment, whereas "others may forego adjuvant treatment altogether."

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