Letter to the Editor regarding the paper by Aurilio et al., A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

Abstract

Sir,We have read with great interest the article in press of Aurilio et al., A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases (http://dx.doi.org/10.1016/j.ejca.2003. 10.004), which will appear in Eur J Cancer. In the paper, the Authors have performed a meta-analysis of the studies published in the literature concerning the discordance rate in oestrogen receptor (ER), progesterone receptor (PgR) and HER2 status between primary tumour and corresponding relapse. It is well known that a considerable controversy concerns the issue of hormone receptors (HRs) expression as well as HER2 status between primary breast carcinomas (BC) and metastatic sites from the same patient, as elsewhere reported in literature [1][2][3][4][5]. In particular, the discordance between primary BC and metastases from negative to positive and vice versa potentially affects the treatment regimen [5]; therefore, it has been suggested that neoplastic tissue of metastatic lesions should be systematically re-biopsied to optimally re-assess HR as well as HER2 [1,2,[4][5][6][7][8].In their meta-analysis, focusing on HER2 status, Aurilio et al. documented that the pooled discordance proportion with respect to the primary breast tumour was 10% for distant metastases and 6% for loco-regional relapses. Moreover, a different pooled discordant proportion was found on the basis of the different utilised technique, since it was 10% in studies using immunohistochemistry (IHC) and fluorescence in situ hybridisation (FISH), but 5% in studies using IHC only; therefore, they conclude the observed discrepancy was not merely due to technicality. Nevertheless, whether these changes in HER2 status may be attributed to laboratory reproducibility in techniques or to other pre-analytical fac-0959-8049/$ -see front matter Ó

Discordance Rate of HER2 Status in Primary Gastric Carcinomas and Synchronous Lymph Node Metastases: A Multicenter Retrospective Analysis

“…Indeed HER2 status has been identified as a significant additional prognostic parameter in advanced GC [ 28 ]. Interestingly, the possible discordance in HER2 status between primary tumour and matched metastases has been shown in both breast and stomach cancers [ 7 , 9 , 10 , 11 , 15 , 19 , 24 , 25 , 29 , 30 ]. As a consequence, the need to assess HER2 status not only in the primary tumour, but also in its metastases, was recently emphasized.…”

“…As a consequence, the need to assess HER2 status not only in the primary tumour, but also in its metastases, was recently emphasized. However, studies investigating the changes in HER2 status mainly considered recurrent, loco-regional or metachronous lesions, while modification in HER2 status between paired primary neoplasm and synchronous nodal metastases was explored in only a few analyses [ 15 , 23 , 25 ].…”

“…This discrepancy may depend upon changes in HER2 receptor expression during the natural history of the tumour and has clinical and therapeutic relevance [ 11 ]. Of note, discordant cases may be characterized by either positive or negative conversion in HER2 status in metastatic asynchronous or synchronous axillary lymph nodes compared to the primary breast carcinoma [ 12 , 13 , 14 , 15 , 16 ].…”

Changes in human epidermal growth factor receptor 2 status between primary breast/gastric carcinomas and synchronous metastatic lymph nodes: how can we explain them?

“…Expression or amplifi cation of human epidermal growth-factor receptor 2 (HER2) frequently occur in primitive neoplastic tissues from patients with breast carcinoma (BC). [1][2][3][4] However, in recent years, several studies have demonstrated that HER2 status may vary in the metastatic lesions compared to the primary tumor, [5][6][7][8] and this discrepancy is more frequently found in distant metastases than in loco-regional ones. [9][10][11][12][13] Discordance in HER2 status was not only found between primary BC and its metastases, but also among the consecutive relapses of the same tumor, with similar proportions of cases turning from negative to positive or vice versa and the changes mainly appeared in the second or following progressions.…”

“…[12][13][14][15] For this reason, some investigators proposed that detection of HER2 status should be re-assessed in the neoplastic tissues from metastatic BC to establish whether the therapy is actually appropriate. [1,2,16,17] Thus, in this study, we evaluated HER2 status in paired samples of BC/GC and synchronous metastatic lymph nodes that were collected during the same surgical and tissue processing procedures, thus limiting and avoiding any potential technical bias due to external factors. Our aim was to explore the eventual HER2 discordance rate between primary BC and GC samples and corresponding lymph node metastases.…”