HER2 Discordance between Primary Breast Carcinoma and Locoregional or Distant Metastatic Disease in Pts Treated in a Single Institution.
Authors: A. Chan, A. Morey
Journal: Cancer Research (2009)

Abstract Background Published data quotes HER2 status discordance rates between primary breast cancer and subsequent metastases of 0-38%. Studies employing immunohistochemistry (IHC) have generally found higher discordance rates than those employing in situ hybridization (ISH), suggesting methodological issues may play an important role in apparent discordance. It has also been proposed that the rate of discordance is higher in metachronous distant metastases than in synchronous or locoregional metastases. This study aims to assess the incidence of true HER2 status discordance between primary and loco-regional or metastatic breast cancer in a cohort of patients (pts) sourced from a single institution, with HER2 ISH-testing from a single reference laboratory with uniform methodology. A secondary aim is to determine the role that intratumoural heterogeneity plays in discordant HER2 status.Method Data collected prospectively for all breast cancer pts treated over the preceding 10 years were reviewed to identify pts with subsequent locoregional or metastatic recurrence where tissue was available from both primary and recurrent lesions. Patient consent was obtained for testing of previously untested samples. HER2 IHC had been previously performed using a variety of assays at local laboratories in 116 paired samples; the remaining samples were centrally tested using DakoA0485 antibody on Ventana XT autostainer. HER2 gene copy was assessed by Ventana INFORM HER2/ch17 SISH probes, with Vysis PathVysion HER2/cep17 dual colour FISH probe employed in cases which were equivocal/non diagnostic by SISH.Results Between 3/1999 and 6/2009, 450 with metastatic breast cancer and 45 pts with local recurrence only were seen. 204 pts (41%) underwent biopsy of the recurrence, where 16 pts had insufficient tissue for analysis in this study. Of the remaining 188 pts, 168 had metachronous recurrent disease (151 metastatic, 37 locoregional) and 20 synchronous metastatic disease, At diagnosis, pts were stage I (22%), II (40%), III (24%), IV (11%), unknown (3%); with mean age 54yrs (range 31-94). Biopsy of recurrence was from breast (20%), Lymph node (19%), Bone (12%), Chest wall (8%), Skin (7%), Liver (7%), Lung (7%), Brain (7%), Other (6%), Pleura (5%), Soft tissue (2%). HER2 IHC testing by local laboratories (116 paired samples) had shown complete concordance between primary and recurrence in only 50 pts (43%). HER2 status in the primary was negative or equivocal (i.e. 0, 1+ or 2+) with conversion to HER2 3+ in the recurrence in 8 pts (6.9%) and the converse in 10 pts (8.6%), resulting in an IHC discordance rate of 15.5%.All tumour samples will be centrally reviewed by ISH to assess for the true rate of discordance between the paired samples. An exploratory analysis of the effect of discordance on response to first-line metastatic treatment and breast cancer outcome will be made.This study was supported by a grant from Roche Australia Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2024.