Abstract P3-05-07: Poor prognosis early breast cancer: pathological characteristics of the Unicancer-PACS08 trial including patients treated with docetaxel or ixabepilone in adjuvant setting
Authors: M Lacroix-Triki, P Delrée, T Filleron, F Penault-Llorca, C Bor, E Mery, V Maisongrosse, P Génin, J Jacquemier, J Reyre, P Caveriviere, M-L Quintyn-Ranty, G Escourrou, C Mesleard, J Lemonnier, A-L Martin, M Campone
Journal: Cancer Research (2012)

Abstract Background: The PACS08 trial aimed to compare adjuvant FEC100-Docetaxel regimen to FEC100-Ixabepilone (Ixa) in poor prognosis early breast cancer (BC). The study population included BC patients presenting with triple-negative (TN) [i.e. estrogen receptor (ER)−/progesterone receptor (PR)−/HER2−] or ER+/PR−/HER2− tumor, which are subgroups significantly associated with worse prognosis. Central review was performed and detailed pathological characteristics of the cohort are reported herein. Patients and method: Between 2007 and 2010, 762 patients with unilateral TNBC (n = 592, 78%) or ER+/PR−/HER2− BC (n = 170, 22%) were enrolled. Recruitment was interrupted due to BMS decision to stop Ixa development in adjuvant setting. As defined by inclusion criteria, TNBC were either node+ or node-, and ER+/PR−/HER2− BC only node+. Following the validation of ER, PR and HER2 status on whole sections prior to inclusion, paraffin blocks (n = 754) were sent for central pathology review, tissue microarray (TMA) construction and constitution of the trial collection for translational research studies. Review of the cases (n = 754) was performed by a board of expert breast pathologists on a one-week working session with discussion of the difficult cases under a multihead microscope. Tumor characteristics were assessed on whole tissue sections. Immunohistochemical detection of Ki67, EGFR, cytokeratins (CK)5/6 and 14, was performed on TMAs. Results: TNBC were significantly associated with younger age at diagnosis (median age 51yr vs 57.5yr in the ER+/PR- subgroup, p &amp;lt; 0.001). Most tumors were invasive ductal carcinomas (72%). Distribution of special histological subtypes was significantly different in the TNBC and ER+/PR−/HER2− subgroups, with the former comprising medullary (n = 16/17) and metaplastic (n = 34/34) subtypes while the latter was enriched in invasive lobular carcinomas (n = 27/35, p &amp;lt; 0.0001). TNBC were significantly associated with higher histological grade as compared to ER+/PR−/HER2− subgroup (Table 1). Accordingly, TNBC displayed significantly higher proliferative activity as shown by mitotic count and Ki67 index (p &amp;lt; 0.001). As compared to ER+/PR−/HER2− subgroup, TNBC showed distinct characteristics, and displayed a so-called basal-like phenotype in 80%. Among the ER+/PR−/HER2− subgroup, most tumors were classified as luminal B (64%). Interestingly, the presence of tumor lymphocytic infiltrate was more frequently observed in luminal B (59%) as compared to luminal A (30%) subtype (p &amp;lt; 0.001). Conclusion: The Unicancer-PACS08 patient cohort is mainly composed of TNBC that harbour distinct pathological features. Description of the PACS08 collection provides a solid basis for translational research projects, which have been initiated with regards to genomic instability and DNA damage repair, immune system, and biomarker studies to identify new therapeutic targets. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-05-07.