Abstract 2903
Background
HER2 overexpression and/or amplification has been reported as predictive factor to HER2 targeted therapy in breast and gastric cancer, whereas HER3 is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 up-regulation in biliary tract cancers (BTCs).
Methods
An electronic search of MEDLINE, ASCO, ESMO and AACR was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridisation (ISH) in BTCs.
Results
Out of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5% (95% CI, 18.9% - 34.1%). Studies were classified as “high-quality” (HQ; 27 studies) [IHC overexpression defined as presence of moderate/strong staining] and “low-quality” (11 studies) [“any” expression was considered positive]. When HQ studies were analysed, extra-hepatic BTCs (EH-BTCs) showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma (IHCC) [19.9% (95% CI, 12.8 – 27.1%) vs. 4.8% (95% CI, 0 – 14.5%); p-value 0.0049]. HER2 amplification rate was higher in those patients selected by HER2 overexpression [57.6% (95% CI, 16.2 - 99%)] compared to “unselected” patients [17.9% (95% CI, 0.1 – 35.4%); p-value 0.0072]. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9% (95% CI, 9.7 - 46.1%) and 26.5% (one study), respectively.
Conclusions
Up to 20% of EH-BTCs might be HER2 overexpressed, ∼60% of HER2 overexpressed BTCs can be considered amplified while HER3 is overexpressed or amplified in ∼25% of BTCs. These findings may be considered in future trial development.
| HER2 status | No. studies | Up-regulation rate mean (95% CI, %) | P-Value | |
|---|---|---|---|---|
| Overall expression by IHC | 38 | 26.5% (18.9 - 34.1%) | ||
| Region of provenience | Asia | 17 | 28.4% (14.5 - 42.3%) | |
| West | 16 | 19.7% (10.1 - 29.2%) | 0.4936 | |
| IHC assessment | Low quality | 11 | 41.7% (22.9 - 60.5%) | |
| High quality | 27 | 20.3% (13.2 - 27.5%) | 0.0336 | |
| Site of Primary regardless IHC scoring | IHCC | 12 | 21.1% (2.3 - 39.7%) | |
| EHBTC | 32 | 22.5% (15.5 - 29.5%) | 0.2557 | |
| EHCC | 11 | 17.4% ( 3.4 - 31.4%) | 0.4752 | |
| GBC | 14 | 24.2% (14.1 - 34.3%) | 0.2339 | |
| AC | 7 | 27.2% (7.2 - 47.2%) | 0.4652 | |
| Site of Primary by HQ/IHC | IHCC | 8 | 4.8% (0 - 14.5%) | |
| EHBTC | 28 | 19.9% (12.8 - 27.1%) | 0.0049 | |
| EHCC | 11 | 17.4% ( 3.4 - 31.4%) | 0.0134 | |
| GBC | 12 | 19.1% ( 11.2 - 26.8%) | 0.0123 | |
| AC | 5 | 27.9% (0 - 60.7%) | 0.0642 | |
| Overall amplification by ISH | 16 | 30.1% (11.7 - 48.5%) | ||
| Site of Primary | IHCC | 6 | 17.6% (0 - 60.1%) | |
| EHBTC | 14 | 22.5% (7.9 - 37.2%) | 0.0468 | |
| Amplification by selection population | No | 12 | 17.9% (0.1 - 35.4%) | |
| Yes | 5 | 57.6% (16.2 - 99%) | 0.0072 |
Clinical trial identification
Legal entity responsible for the study
Istituto Europeo di Oncologia, Milano (IT)
Funding
“Clinical Unit Visit” ESMO fellowship
Disclosure
All authors have declared no conflicts of interest.