At median follow up of more than 7 years, the relapse-free survival (RFS) and overall survival (OS) rates for the whole group of 264 patients treated at Colorado were 69.8% and 73%, respectively. The median time to relapse was 14 months (63.5% relapses within the first 2 years, 6.7% after the 5th year).
We identified three clinical variables independently associated with outcome: nodal ratio (number of involved nodes/number of dissected nodes), pathological tumor size, and hormone receptors [2]. A scoring system was constructed with those variables: score = (nodal ratio × 3.05) + (tumor size × 0.15) - (ER/PR × 1.15). In this formula, size is entered in cm, and ER/PR is assigned '1' if positive (estrogen receptor [ER] and/or progesterone receptor [PR] positive), or '0' if negative (both negative). A cutoff score of 2.41 yields the best sensitivity and specificity. Thus, patients with low (<2.41) and high (≥ 2.41) scores before transplant presented significant differences in outcome. This model was validated in an external sample of 225 HRPBC patients treated at Duke University with the same HDC. It was subsequently validated prospectively in our second patient cohort [3].
Overexpression of HER2, identified as an independent predictor of outcome, complemented the clinical model, establishing the following risk groups: low risk (low score, HER2-negative; 44% patients; 87% RFS), intermediate risk (low score, HER2-positive; 29% patients; 68% RFS), high risk (high score, any HER2; 27% patients; 49% RFS) [4].
We detected an independent prognostic effect of EGFR (epidermal growth factor receptor), particularly among HER2-positive patients [5], which suggests a synergistic effect through heterodimerization of both receptors. In contrast, we did not observe a prognostic effect of p53 status [4].
Tumor angiogenesis, assessed through CD31-stained microvessel count, was an independent adverse predictor of outcome [6]. In contrast, tumor VEGF (vascular endothelial growth factor) expression lacked prognostic significance in our population with locoregionally advanced tumors, in contrast to multiple prior observations in patients with earlier disease [6].
Finally, we observed that the presence of tumor cells contaminating the apheresis product, detected through immunocytochemistry for cyto-keratins, was independently associated with post-transplant relapse [7].