Molecular Markers Predict Clinical Outcome

PARIS, France--University of Chicago researchers have discoveredthat the combination of a molecular marker of tumor virulenceand a marker of metastatic potential can be used to reliably predictoutcome in women with node-negative breast cancer, Ruth Heimann,MD, PhD, reported at the annual meeting of the American RadiumSociety.

"Scoring tumor microvascular density adds significant prognosticinformation in addition to tumor size, nuclear grade, and estrogen-receptor(ER) status," Dr. Heimann said.

From a database of 826 node-negative mastectomy patients, fewof whom had received adjuvant chemotherapy, Dr. Heimann and hercolleagues were able to retrieve archival material on 184 womenwith mostly small tumors.

They chose ER status as an indicator of virulence, or the paceof tumor growth, and used microvascular density, assessed withfactor VIII antibody, as a marker for metastagenicity, or theultimate likelihood of distant metastases.

Although in postmenopausal women, ER status had no impact on 20-yeardisease-free survival, premenopausal women who were ER positivedid significantly worse than their receptor-negative counterparts,Dr. Heimann noted.

She hypothesized that these apparently paradoxical results mightbe attributable to the maturity of the database, pointing outthat the same phenomenon has been documented at Sloan-Kettering.

"When we looked at disease-free survival based on microvesseldensity, we identified a group of patients with low microvesseldensity who had significantly better long-term disease-free survivalthan those with high microvessel density," Dr. Heimann said.She emphasized that the favorable prognostic weight of low microvasculardensity held for women with ER-positive tumors as well as forthose with nuclear grade 2 or 3 tumors.

The Chicago team was able to define three distinct prognosticgroups on the basis of the combination of microvascular density,ER status, and nuclear grade:

• Women with low microvascular density had a better than 90%chance of surviving for 20 years with no signs of disease.
• In contrast, 20-year disease-free survival was only 60% inwomen with all three markers at their worst--more than 15 microvesselsper high-power field, ER positivity, and nuclear grade 2 or 3.
• An intermediate outcome was seen in women with high microvasculardensity, ER negativity, and nuclear grade 1.

"Adjuvant chemotherapy may need to be modified accordingto prognostic markers," Dr. Heimann suggested. "Thequestion is how to further improve our ability to predict outcomeabove the 90% level and below the 60% level, and our strategyis to add other markers and retrieve more tumor material,"she said.