Aim: To describe the effects of the development, implementation and prospective systematic evaluation and adaptation of a clinical care pathway for the management of patients with early breast cancer between 2002 and 2010) in a single breast unit. Materials and methods: In 2002 a clinical pathway was developed by the multidisciplinary breast team of the Sint Augustinus Hospital for de diagnosis and treatment of patients with operable breast cancer. Performance measurements were documented systematically by care providers using an order communication, planning and result reporting system. Annual analysis of predefined clinical outcome measures and indicators was performed. Based on these data and evidence based guidelines the pathway was regularly adapted to improve patient care. Results: The annual number of patients included in the pathway (289 vs 390, p 0.01) ), proportion of patients with Tis-T1 tumors (42% vs 58 %, p 0.01), negative lymph nodes (44% vs 58%, p < 0.01)) and no metastases at diagnosis (91.5% vs 95.9%) has risen significantly between 2002 and 2010. Histological subtypes remained the same. The average length of hospital stay (7.0 days vs 4.1 days, p 0.01) nearly halved and the proportion of breast conserving surgery (BCS) (43% vs 57%), preoperative guide wire localization (14% vs 27%) for impalpable lesions and use of sentinel node biopsy (0% vs 49%) increased significantly (p 0.01). Evolution of quality indicators defined by Eusoma (www.eusomadb.org/indicators.htm) between 2002 and 2010 shows a significant improvement of cancer care: proportion of positive of preoperative histologic diagnosis (59.7% vs 88.4%, p 0.001), more then 9 lymph nodes removed when axillary clearance performed (85.6 vs 91.4%, p< 0.04), BCS for invasive carcinoma up to 3 cm (62.0% vs 82.6%, p 0.016), BCS for DCIS up to 20 mm (43.8% vs 78.6%, p 0.016), hormone therapy in endocrine sensitive tumor (84.8% vs 97.4%, p 0.002), adjuvant chemotherapy in ER negative (PT1c or N+) invasive carcinoma (72% vs 95.6% p 0.028), proportion of second surgery (25% vs 10%, p 0.001) and clear margins after last operation (95% vs 99%, p 0.02). All mandatory EUSOMA requirements were fulfilled in 2010. Patient satisfaction improved significantly over the years (13/19 measured parameters p <0.05 between 2002–2010). Progression free 4 year survival was significantly higher for all patients, for T1 tumors only and for T2-T4 tumors only, treated in 2006–2008 compared to 1999–2002 and 2003–2005 (respectively p 0.006, p 0.05, p 0.06). Overall 4 year survival of the entire M0 population treated in 2006–2008 was significantly better (p 0.05) Conclusion: Although the patient characteristics changed over the years due to better screening, this clinical pathway for the treatment of patients operable breast cancer proved to be an important tool to improve the quality of patient care and patient satisfaction. Better adherence to guidelines and constant feedback of treatment data to the breast team contributes to a superior patient outcome. Measuring quality indicators proved useful to develop quality measures improving patient care. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-06.

Introduction. Breast cancer can be divided into several subgroups characterized by unique patterns of pathway activation. Platelet-derived growth factor receptor (PDGFR) signalling has not yet been included in this classification scheme, although it has been reported to be a potential target for therapy. In this study, we have constructed a PDGFR-activation signature and investigated its relevance in breast cancer. Materials and Methods. Sixteen PDGFR-modulated genes were identified by intersecting two published PDGFR-modulated gene lists. The resulting gene signature was applied onto a publicly available gene expression data set of GIST (GSE17743) using principle component analysis. The segregation of PDGFR- and KIT-mutated GIST samples was investigated using permutation analysis and classification sensitivity and specificity were assessed. Using the regression coefficients from the first principal component, a PDGFR-activation score was constructed and applied onto a second data set in order to validate the score (GSE1923). Finally, the score was applied onto a gene expression data set of 389 breast cancer ***samples, including 137 samples from patients with IBC. Results. Sixteen PDGFR-modulated genes (NR4A1, EGR3, JUNB, IER3, TIEG, JUN, BCL3, MYC, NR4A3, PLAU, MCL1, DUSP1, DUSP5, DUSP6, SGK, GADD45A) were able to discriminate PDGFR-mutated GIST samples from KIT-mutated GIST samples with a sensitivity of 75% and a specificity of 85%. Application of the PDGFR-activation score onto a data set of control and PDGF-treated glioblastoma cells showed a significant increase in the PDGFR-activation score in the treated condition (P=0.0302). Application of the PDGFR-signature onto our series of IBC and nIBC samples demonstrated a significant and molecular subtype-independent increase in PDGFR-activation in IBC (P=0.0015; FDR=3%). In addition, in our series of nIBC samples only, PDGFR-activation was associated with decreased DMFS and RFS (P=0.0038 and P=0.0137 respectively). In fact, PDGFR-activation was an independent prognosticator in a multivariate model incorporating the molecular subtypes. Discussion. We identified a gene signature composed of 16 genes able to predict PDGFR-activation in tissue samples by gene expression analysis. PDGFR-activation is significantly increased in samples from patients with IBC, an aggressive form of locally advanced breast cancer. In addition, in nIBC, PDGFR-activation is associated with DMFS and RFS, independently of the molecular subtypes suggesting that PDGFR-activation might add another level of clinically relevant heterogeneity in breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-01.