A predictive model for relapse in high-risk primary breast cancer patientstreated with high-dose chemotherapy and autologous stem-cell transplant

High-dose chemotherapy (HDCT) is currently under evaluation for high-risk p rimary breast cancer (HRPBC), defined by extensive axillary nodal involveme nt or inflammatory breast carcinoma. Phase II studies of HDCT for HRPBC sho w that 30-40% of patients eventually relapse, We retrospectively reviewed 1 76 patients enrolled in clinical trials of HDCT for HRPBC at the University of Colorado and analyzed 23 potential predictive variables for relapse. Al l of the patients received the same regimen, with cyclophosphamide, cisplat in, and BCNU, Nine patients who experienced a toxic death were excluded fro m this analysis. The resulting predictive model was subsequently tested in an independent patient set treated at Duke University with the same HDCT re gimen. Nodal ratio (number of involved nodes:number of sampled nodes), tumo r size, grade, stage, estrogen receptor, progesterone receptor, and clinica l inflammatory breast carcinoma correlated with risk of relapse. Nodal rati o, tumor size, and the combined estrogen receptor/progesterone receptor sta tus were independent predictors. A scoring system using those three variabl es determines the risk of relapse, with a sensitivity and specificity of 60 and 90%, respectively, and a positive and negative predictive value of 65 and 88%, respectively. The differences in relapse-free survival and overall survival between high- and low-score patients were highly significant (P < 0.000001), This model was subsequently validated in the Duke patient set. This model can identify two subgroups of HRPBC patients with low (12%) and high (65%) risk for recurrence after HDCT, Future research that tests new t herapies will focus on those patients with a high score.