Association of osteopontin with specific prognostic factors and survival in adjuvant breast cancer trials of the Hellenic Cooperative Oncology Group

Additional file 1. OPN supplementary data

Comparison of the Ability of Different Clinical Treatment Scores to Estimate Prognosis in High-Risk Early Breast Cancer Patients: A Hellenic Cooperative Oncology Group Study.

Early breast cancer is a heterogeneous disease, and, therefore, prognostic tools have been developed to evaluate the risk for distant recurrence. In the present study, we sought to develop a risk for recurrence score (RRS) based on mRNA expression of three proliferation markers in high-risk early breast cancer patients and evaluate its ability to predict risk for relapse and death. In addition the Adjuvant! Online score (AOS) was also determined for each patient, providing a 10-year estimate of relapse and mortality risk. We then evaluated whether RRS or AOS might possibly improve the prognostic information of the clinical treatment score (CTS), a model derived from clinicopathological variables.A total of 1,681 patients, enrolled in two prospective phase III trials, were treated with anthracycline-based adjuvant chemotherapy. Sufficient RNA was extracted from 875 samples followed by multiplex quantitative reverse transcription-polymerase chain reaction for assessing RACGAP1, TOP2A and Ki67 mRNA expression. The CTS, slightly modified to fit our cohort, integrated the prognostic information from age, nodal status, tumor size, histological grade and treatment. Patients were also classified to breast cancer subtypes defined by immunohistochemistry. Likelihood ratio (LR) tests and concordance indices were used to estimate the relative increase in the amount of information provided when either RRS or AOS is added to CTS.The optimal RRS, in terms of disease-free survival (DFS) and overall survival (OS), was based on the co-expression of two of the three evaluated genes (RACGAP1 and TOP2A). CTS was prognostic for DFS (p3 positive nodes (LR-Δχ2 23.9, p3 positive nodes

Prognostic information among models used in terms of DFS.

<p>Prognostic information among models used in terms of DFS.</p

Prognostic information of CTS and improved significance when adding RRS or AOS to CTS.

<p>Changes in the likelihood ratio (LR) values (LR-Δχ²) are shown in the y-axis for disease-free survival (left panel) and overall survival (right panel).</p

Discrimination power by the concordance index (C-index) for the three scores alone and their combinations.

<p>C-indices by IHC subtypes, HER2 status and number of positive nodes are shown in the x-axis for disease-free survival (left panels) and overall survival (right panels).</p

Photos of TMA and whole tumor sections

Primary image data of TMA and whole tumor section

Ten-year risk estimates for CTS, AOS and RRS according to risk class categories.

<p>Risk for relapse is shown in the left panels and risk for death in the right panels, according to low, medium and high CTS and AOS. For RRS, two risk classes were available, with the red bars representing the risk for patients with high mRNA expression for both RACGAP1 and TOP2A and the blue bars when at least one of the genes had low mRNA expression (numbers on bars: percent of 10-year risk estimate).</p