Pathological Comparison of Breast Cancer Metastases with Primary Tumours in a Large Prospective Trial Testing Whole Genome Approach
Magali Lacroix-Triki, Isabelle Treilleux, Marie-Christine Mathieu, Delphine Loussouarn, Gaetan Mac Grogan, Anne Vincent-Salomon, Frederique Penault-Llorca, Thomas Filleron, Thierry Dubois, Thomas Bachelot, Frederic Commo, Mario Campone, Marta Jimenez, Fabrice Andre. Institut Claudius Regaud, Toulouse, France; Centre L Bérard, Lyon, France; Institut Gustave Roussy, Villejuif, France; CHU, Nantes, France; Institut Bergonié, Bordeaux, France; Institut Curie, Paris, France; Centre Jean Perrin, Clermont-Ferrand, France; Centre R Gauducheau, Saint Herblain, France; R&D UNICANCER, Paris, France
Background: Owing to the report of biomarker switch between primary and recurrent breast cancer, several groups recommend to re-sample metastatic sites. In the prospective SAFIR01 trial, systematic biopsies of metastatic sites were performed for genomic analysis to direct patients to specific targeted agents. We report the practical feasibility of molecular characterization on metastasic biopsy specimens and pathological comparison to matched primary tumours.
Design: From 2011 to 2012, 423 patients with metastatic breast cancer were included. Biopsies of metastatic sites were performed: at least two samples were snap-frozen and the remaining fixed in formalin (FFPE). DNA was extracted from the frozen sample, provided that it contained >50% cancer cells, and subjected to CGH array and sequencing of PIK3CA and AKT. When sufficient FFPE material was available, hormone receptor (HR) and HER2 status was re-assessed according to local institution protocols. Primary tumour characteristics were extracted from the initial pathology report and tumour collected for re-testing when available.
Results: Metastasis biopsy was successful in 97% and involved the liver (40%), lymph nodes (17.5%), skin (16%), lung (6.5%) and other sites (20%). Tumour cell content was sufficient to proceed to DNA extraction in 73% of the cases, allowing CGH array and sequencing for at least 68% of the patients. Mutation of PIK3CA and AKT were observed in 24% and 4.5% of the samples respectively. Most frequent genomic alterations consisted of amplification of FGF4 (16%), HER2 (13%) and FGFR1 (11%), with a constellation of rarer (<5%) actionable genomic changes in about 20% of the cases. Among the 204 cases available for comparison analysis with regards to HR status, 19% were discordant, with a loss of HR expression in 62% of these cases. As for HER2, 8% of discordant cases were observed, mainly represented by a loss of HER2 expression in 60% of these cases.
Conclusions: The discrepancy rates between primary and metastases for HR and HER2 in the SAFIR01 study are similar to those described in the literature. In this large prospective trial, we have shown that whole genome DNA approach is feasible in the context of daily practice to identify actionable alterations and direct patients to specific targeted agents.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 22, Wednesday Morning