Long-Term Analysis and Prospective Validation of a Prognostic Model for Patients with High-Risk Primary Breast Cancer Receiving High-Dose Chemotherapy

Abstract

Purpose: We described previously a prognostic model for high-risk primary breast cancer patients receiving highdose chemotherapy (HDC). Such model included nodal ratio (no. involved nodes:no. dissected nodes), tumor size, hormone receptors, and HER2. In the present study we intended to test this model prospectively in a second patient cohort. In addition, we analyzed the long-term overall outcome of our HDC trials.Experimental Design: We analyzed all 264 patients enrolled since 1990 in our prospective trials for 4 -9؉, >10؉ nodes, or inflammatory disease. Patients of the second cohort (treated since 1997) had their prognostic score estimated prospectively before receiving HDC.Results: Fourteen patients (5.3%) died from HDCrelated complications. At median follow-up of 7.1 years, relapse-free survival and overall survival of the whole group were 69.8% and 73%, respectively. Median time to relapse was 14 months (63.5% relapses within the first 2 years, 6.7% after year 5). The model was validated in the second cohort, establishing the following pretransplant risk categories: low risk (low score, HER2؊), 44% patients, 87% freedom from relapse (FFR); intermediate risk (low score, HER2؉), 29% patients, 68% FFR; and high risk (high score, any HER2), 27% patients, 49% FFR.Conclusions: Few relapses are seen after year 5 of follow-up, which indicates the need for mature results of the randomized trials before their final interpretation or metaanalysis. Our prospectively validated prognostic model, if additionally confirmed in the randomized trial populations, may provide an insight into the relative benefit of HDC in different risk patient subsets.

Prognostic analysis of tumour angiogenesis, determined by microvessel density and expression of vascular endothelial growth factor, in high-risk primary breast cancer patients treated with high-dose chemotherapy

“…The optimal cutoff score of 2.41, as identified in the receiver operating characteristic curves, conferred on the model a sensitivity of 0.6, a specificity of 0.88, a positive predictive value of 0.65, a negative predictive value of 0.86, and an accuracy of 83%. The prognostic value of this score was confirmed externally (Nieto et al, 1999) and prospectively (Nieto et al, 2004).…”

“…We retrospectively analysed tumour samples from patients who were prospectively enrolled in phase II and III trials of HDC for HRPBC at the University of Colorado between 1990 and 2001. A total of 234 patients were accrued in these studies, which were open to patients with 4 -9 positive axillary nodes (n ¼ 102) (Bearman et al, 1997;Moore et al, 2007) and 10 or greater positive nodes (n ¼ 132) (Nieto et al, 2004;Peters et al, 2005). Those trials, as well as the current retrospective review of tumour blocks, were approved by the Cancer Center Protocol Review Committee and the Institutional Review Board.…”

The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

“…Furthermore, previous studies demonstrated that normalisation of an initial lymphocytopenia resulted in an improved clinical outcome in breast cancer patients treated with chemotherapy (Nieto et al , 2004; West et al , 2011). An elevated lymphocyte count has also significantly been associated with prolonged OS in patients with multiple myeloma and metastatic colorectal cancer (Leitch et al , 2007; Ege et al , 2008).…”

The elevated preoperative derived neutrophil-to-lymphocyte ratio predicts poor clinical outcome in breast cancer patients

“…The importance of lymphocytes has been demonstrated in several studies in which an increased infiltration of tumors with lymphocytes has been linked with improved outcomes in cancer patients [33][34][35][36]. Additionally, elevated peripheral blood lymphocyte counts have been correlated with prolonged survival in various types of cancer, whereas low peripheral blood lymphocyte counts have been linked with cancer progression and poor prognosis [22,[37][38][39][40]. A high dNLR might be caused by an elevated neutrophil count and/or a low lymphocyte count and likely reflects a more aggressive behavior of tumors.…”