Her2 Expression in Circulating Tumor Cells Is Associated with Poor Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

HER2-dependent signaling may support the development of metastatic castration-resistant prostate cancer (mCRPC) by activating androgen receptor signaling through ligand-independent mechanisms. From 41 mCRPC patients (including 31 treated with Androgen Receptor Signaling Inhibitors [ARSI]), Circulating Tumor Cells (CTCs) were prospectively enriched with AdnaTest platform and analyzed with a multiplexed assay for HER2 and AR-V7 mRNA expression. Then, we evaluated the impact of HER2 expression on PSA-response, Progression Free Survival (PFS) and Overall Survival (OS). HER2 expression was detected in CTCs of 26 patients (63%). Although PSA response was similar regardless of HER2 status, patients with HER2 positive CTCs had shorter PSA-PFS (median: 6.2 months versus 13.0 months, p = 0.034) and radiological-PFS (6.8 months versus 25.6 months, p = 0.022) than patients without HER2 expression. HER2 expression was also associated with a shorter OS (22.7 months versus not reached, p = 0.05). In patients treated with ARSI, multivariate analyses revealed that the prognostic impact of HER2 status on PSA-PFS was independent of AR-V7 expression and of the detection of CTCs by an AdnaTest. We showed for the first time the poor prognostic value of HER2 expression in CTCs from patients with mCRPC. The therapeutic interest of targeting this actionable pathway remains to be explored.

Assessment of the expression pattern of HER2 and its correlation with HER2-targeting antibody-drug conjugate therapy in urothelial cancer

“…Some studies have attempted to detect HER2 expression in circulating tumor cells. 39 Based on this, we can reasonably speculate that precision detection and evaluation may become future research hotspots.…”

A Systematic Review of Circulating Tumor Cells Clinical Application in Prostate Cancer Diagnosis

“…After applying all the selection criteria, the final sample comprised 46 articles on metastatic PC [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ] ( Supplementary Table S1 ) and 15 articles on localized PC [ 55 , 56 , 57 , 58 , 59 , 60 …”

HER2 as a potential therapeutic target on quiescent prostate cancer cells

“…They also found that HER2 (ERBB2) was enriched in experimental bone metastases and that dual inhibition of EGFR and HER2 was required for effective bone metastasis treatment [20] . On a related note, Maillet et al fround that HER2 expression by circulating tumor cells in patients with metastatic castration resistant PCa correlated with worse clinical outcome, most importantly overall survival [33] . In testing response of PCa cell lines to trastuzumab (anti-HER2) and cetuximab (anti-EGFR), Andersson et al did not observe additional effects of addition of cetuximab to trastuzumab.…”