New approach to genomic testing identifies women with low risk of breast cancer recurrence

Dec 13 2004

An initial validation study presented by Exagen Diagnostics at the San Antonio Breast Cancer Symposium suggests it may soon be possible to distinguish good prognosis from poor prognosis in any newly diagnosed breast cancer patient based on DNA changes in the patient's tumor.

Those patients identified as having a very good prognosis may do well without chemotherapy or hormonal therapy after their tumors have been removed.

In a retrospective study of 308 patients conducted with the University of New Mexico Cancer Research and Treatment Center at the Health Sciences Center, Exagen Diagnostics, an emerging leader in the rapid identification and productization of practical, genomic markers for prognostic testing, reported the discovery of two, 3-gene sets of markers that were prognostic in testing archived specimens from hormone receptor (HR)-positive and hormone receptor-negative patients, respectively. These two sets of markers form a panel for use in testing tumor tissue from breast cancer patients, providing a same- or next-day result.

In independent test sets, each of the 3-gene markers accurately identified 91 percent of HR-negative and HR-positive specimens from patients that did not experience recurrence of disease. In patients that were also node negative, the negative predictive value was 100 percent (e.g., 100 percent of patients identified by these tests had a good prognosis clinically).

The study population consisted of white and Hispanic patients with invasive ductal carcinoma that were diagnosed between 1986 and 1999 at the University of New Mexico Health Sciences Center. A minimum of four years of follow-up clinical information was available for each of the patients, with an average follow-up of 8.9 years. Poor prognosis was clinically defined as development of recurrence, as evidenced by either distant metastasis or death from breast cancer. Good prognosis was clinically defined as the absence of recurrence (or death from breast cancer) as of the last date of follow-up.

"With this approach, we are seeking to define a new standard of care by becoming the first company to offer a prognostic panel of tests that examines the patient's tumor tissue to detect changes in DNA copy number in any patient. This is a more practical method than currently available tests using RNA," said Waneta Tuttle, Ph.D., Exagen CEO.

"Today, we are treating almost any woman as though her cancer is aggressive, which puts patients who don't actually need treatment at risk for side-effects of therapy that is not necessary," explains Ian Rabinowitz, M.D., the primary UNM clinician involved in Exagen's initial study. "For early stage breast cancer there are about 70 to 80 percent of patients who are cancer-free and don't actually require therapy after they receive a lumpectomy. At this point in time, we have no way of identifying which patients fall into that category. So, the advantage of a technology such as Exagen's prognostic tests, once it is further validated, is that we can better identify patients that have a very good prognosis and potentially don't actually require therapy," he said.

The study was conducted using a proprietary "pattern of genomic amplification" FISH (e.g., fluorescent in situ hybridization) test or PGA FISH(TM). Due to the small number of markers in each reagent set, Exagen is uniquely able to implement these tests with PGA FISH technology, making them readily usable by any FISH-testing laboratory. Exagen's discovery technology is based on a mathematical approach that enables the company to examine 25,000 genes with no "preference" for one gene over another to define the best, small combination of genes for a specific testing purpose.