Gene Signature Associated with Prognosis

Genomic Health has commercialized a new test which has been shown to be associated with risk of tumor recurrence for stage II colon cancer. The test came on the market in January of 2010.

I wanted to review with you the limitations of this test, which is  not as good by far as the test they have developed for breast cancer.

Stage II colon cancer is usually a T3 N0 lesion meaning there are no lymph nodes involved. Oncologists look very carefully at the pathology report to make sure there are no aggressive features seen such as invasion into the nerves or blood vessels or tumor cells which are poorly differentiated (which means you can’t really see where the cell comes from). These features would already indicate a higher risk of tumor recurrence.

We have other clinical features such as signs of bowel obstruction or when the surgeon removed less than 12 lymph nodes that tell us the patient has higher risk, and we usually recommend 6 months of chemotherapy.

For patients who have none of these risk factors the risk of tumor recurrence for stage II colon cancer is about 15 percent. The dilemma is what we don’t know whether the individual patient will recur or not.

The Oncotype DX®  for colon cancer measures 12 genes in the tumor tissues and separates the tumor into  low, intermediate, and high risk for recurrence. Low risk is 12%, intermediate 18% and high risk is 22%. The distinction between risk levels is much less than for breast cancer where low risk is 7% and high risk is 31%, and therefore is much less clinically helpful.

However the biggest difference between the breast and colon tests is that in the breast test the benefit from adjuvant chemotherapy is known, but for colon we don’t know if chemotherapy has any benefit in any of the risk categories.

We need a better signature to distinguish between low and high risk.  Twelve to 22 percent is only a small step, and not satisfactory to make treatment decision not knowing if there is any treatment effect. In other words your risk of 12% could mean you benefit from chemo but your risk of 22% may not.

Many companies are working on prognostic markers which can help to select patients at high risk much better for chemotherapy, I have not adapted this test for evaluation for my patients with stage II colon cancer.

Disclosure: Dr. Lenz serves as a consultant to Amgen, Bristol-Myers Squibb, Genentech, ImClone, Merck KG, Novartis, Pfizer, Response Genetics, and sanofi-aventis. He has received honoraria from Astra Zeneca, Bayer, Bristol-Myers Squibb, Eli Lilly, Genentech, ICN, Imclone, Millenium, New Biotics, Novartis Chiron, Pfizer, Roche, sanofi-aventis. His research is funded by the National Cancer Institute and the National Institutes of Health

Disclosure:  Dr. Lenz is a consultant to Response Genetics which markets a genetics test to help patients and doctors make treatment decisions.

Disclosure: C3 has received funding from Genomic Health in the form of unrestricted educational grants.  C3 has ultimate authority over website content.