Abstract P2-05-06: Clinical utility of systematic biopsy of first metastatic event in breast cancer: Results from a prospective multicenter trial

BACKGROUND : Cumulative evidence for phenotypic and molecular heterogeneity between primary breast cancer (BC) site and matched metastasis (mets) has been obtained in retrospective studies. Current expert consensus suggests performing biopsies of mets, but clinical utility and cost are unknown. The primary objective of the ESOPE study (NCT01956552) was to compare the phenotype and genotype of the primary tumor (PT) with those of matched mets at time of first distant relapse, before the start of any treatment, in order to optimize the treatment of mets PATIENTS and METHODS : Between Nov. 2010 and Sept. 2013, we conducted a prospective multicenter study on BC patients (pts) with diagnosis of first mets. All pts were to have available Formalin-Fixed Paraffin-Embedded (FFPE) PT sample and mets accessible to either percutaneous or surgical sampling. All tissue samples were centrally analyzed with immunohistochemistry (ER, PgR, HER2, and Ki67) and FISH when indicated. Frozen samples were stored for further analyses. We recorded intended therapeutic decision before and after biopsy. RESULTS : Of 93 pts included, 89 were eligible for biopsy. Median age was 57 years (28-81); median interval between PT and mets was 42 months (0-211), including 14 pts with novo metastatic breast cancer. Mets biopsy was performed in 85 pts (96%, refusal n=2, not feasible n=2). Toxicity was limited to only 1 grade 1 hemorrhage. Sampled sites were liver (44%), lung (16%), bone (13%), lymph node (13%), skin/muscle/chest wall (9%), ovary/peritoneum (4%), and adrenal gland (1%). PT was not available in 4 pts; mets biopsy was non contributive in 6 pts but led to a diagnosis of second primary cancer in 3 pts. In 72 pts with matched PT and mets, PT were luminal A (n=11), luminal B (n=33), triple negative (n=13), HER2 (n=13), non-evaluable (n=2). Mets were luminal A (n=6), luminal B (n=30), triple negative (n=16), HER2 (n=14), non-evaluable (n=6). Discrepancy rates were: ER 18% [kappa for concordance =0.6, CI 95 % (0.42-0.77)], PgR: 39% [kappa=0.19, CI 95% (0.01-0.39)], Her2: 4% [kappa=0.86, CI 95% (0.7-1)], Ki67: 25% [kappa=0.19, CI 95% (-0.09; 0.49)]. The most frequent discrepancy rate was observed in pts with lum A PT, as only 3/10 developed Lum A mets. HER2 and triple negative were the most stable subtypes (12/13 and 12/12 respectively). Most importantly, mets biopsy led to a change in therapeutic decision in 25 pts (independent evaluation by 2 oncologists). Additional comparative targeted NGS analyses are ongoing on a first subset of 54 FFPE paired samples, and parallel whole exome sequencing is planned on 38 paired samples with available constitutional DNA. CONCLUSION : Comparative analysis of breast cancer PT and first mets is routinely feasible, with very low morbidity and a significant impact for patients9 management: 29% had a second cancer diagnosis or were proposed a therapeutic change. Furthermore, this study will provide additional data on quality and quantity of tissue available for molecular analysis, and ultimately in terms of cost-efficacy. Citation Format: Comte A, Sigal-Zafrani B, Belin L, Bieche I, Callens C, Dieras V, Bidard F-C, Mariani O, Servois V, Szwarc D, Vincent-Salomon A, Brain ECG, Cottu PH. Clinical utility of systematic biopsy of first metastatic event in breast cancer: Results from a prospective multicenter trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P2-05-06.