Experimental Prognostic Test Identifies Breast Cancer Patients at Greatest Risk for Metastasis

Objective Tool May Help Patients Avoid Chemotherapy


- An experimental prognostic assay that, at the time of diagnosis, identifies which breast cancer patients are at greatest risk for metastatic disease did so
with more than 90 percent sensitivity, according to a study published in The Lancet (February 19, 2005; vol. 365: issue 9460). The assay represents the
first prognostic molecular marker that could be used with all lymph-node-negative (LNN) breast cancer patients, regardless of age, tumor size and grade,
or estrogen receptor/progesterone receptor (ER/PR) status. This diagnostic tool is being developed by Veridex, LLC, a Johnson & Johnson company.



Once the new genomic assay is further developed for commercial use, oncologists could have access to reliable and objective information not previously
available with this level of sensitivity to assess individual risk in a broad range of LNN breast cancer patients. Having such knowledge will help physicians
and patients make more individual and effective decisions regarding post-surgical therapy; most notably, the 76-gene signature, on which the assay is
based, could help identify patients who may not require adjuvant chemotherapy or could undertake a less-aggressive course of treatment.


"These findings could one day profoundly change treatment standards for lymph-node-negative breast cancer patients by more precisely determining who
is at risk of metastasis," said David Atkins, Ph.D., general manager, Molecular Diagnostics, Veridex, LLC, and a senior author on the study. "This purely
prognostic tool, which is the only one of its kind that can be used with such a broad range of patients, marks a significant step toward a time when
oncologists have the information to make quantitative, objective, effective treatment choices tailored precisely to each patient's unique risk profile."



The work represented a collaboration between the Erasmus Medical Center - Daniel den Hoed Cancer Center in Rotterdam, Netherlands, and Veridex,
LLC. Researchers analyzed tumor samples of 286 breast cancer patients treated during 1980-95, all of whom were lymph-node negative and did not
receive adjuvant chemotherapy. Importantly, the samples represented patients from routine practice, from all age groups and who were both ER/PR
positive and negative.


A genomic signature was constructed using gene expression data of 76 genes derived from extensive tumor gene expression profiling by Veridex, LLC,
researchers. This signature showed 93 percent sensitivity and 48 percent specificity in a subsequent independent testing set of 171 LNN patients. The
gene profile was highly informative in identifying patients who developed metastatic disease within five years; it also was a strong prognostic indicator of
development of metastases in the subgroups of 84 premenopausal and 87 postmenopausal patients, and in patients whose tumors measured 10-20 mm,
a group for whom prediction of prognosis is especially difficult.


According to John Foekens, Ph.D., and Jan Klijn, M.D., the study's lead investigators at Erasmus Medical Center, there have been many attempts to find
novel markers to identify breast cancer patients at risk for progression, but few have been implemented in routine practice due to their lack of wide
applicability or low prognostic power. Currently available tools are generally restricted to patients with a specific ER status, or to patients already taking
tamoxifen.


"These signatures represent a future of hope for improved treatment customization, but much more research needs to be done before they are made
available in routine clinical care," said Klijn, a medical oncologist.


This prognostic signature was later independently validated in a separate consecutive series of approximately 150 patients from four medical institutions.
The results were presented at the 2004 San Antonio Breast Cancer Symposium. Although this prognosticator has now been validated in approximately
320 patients, investigators are currently pursuing a further rigorous multi-institution clinical evaluation of the signatures.


About Veridex, LLC


Veridex, LLC, a Johnson & Johnson company, develops cancer diagnostic products that will enable earlier disease detection as well as more accurate
staging, monitoring and therapeutic selection. The company is initially developing two complimentary product lines: CellSearch™ assays that identify,
enumerate and characterize circulating tumor cells directly from whole blood; and GeneSearch™ assays that use molecular technology to diagnose,
stage and more accurately characterize tumors. For more information, please visit veridex
.