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Table 1 Literature review of studies relating to HER3 prognostics in human breast cancer

From: Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4–1 and NRDP1, in primary breast cancer

Publication by Laboratory Methodology Cohort Characteristics Prognostic Implications
Takada et al. [91] IHC (RTJ2) met-HER2+ BCA (n = 29), TPD ↓ Low HER3 expression was associated with shortened PFS
Adamczyk et al. [25] IHC (SP71) HER2+ BCA (n = 97), Adj.T ↑ High HER3 expression (only with concurrent PTEN negativity) was associated with shorten MFS
Duchnowska et al. [44] VeraTag assay HER2+ BCA (n = 189), Adj.T - No correlation between HER3 expression and OS in advanced stage HER2 + BCA
Nishimura et al. [54] VeraTag assay met-HER2+ BCA (n = 47), T - HER3 expression did not has any influence on PFS in trastuzumab-refractory advanced HER2 + BCA
Koutras et al. [39] qRT-PCR BCA (n = 663, HER2 + BCA n = 143) ↓ Low HER3 mRNA (only with concurrently high EGFR, high HER2, low HER4 mRNA) was associated with worse DFS
Baselga et al. [38] qRT-PCR*, IHC** (DAK-H3-IC) HER2+ BCA (n = 740*/497**), Adj.T ↓ High HER3 mRNA was associated with better prognosis in metastatic HER2 + BCA
Berghoff et al. [16] IHC (DAK-H3-IC) met-BCA (n = 110, met-HER2 + BCA n = 34) ↑ High HER3 expression was associated with shorter OS in initially metastatic HER2 + BCA subgroup
Park et al. [31] IHC (DAK-H3-IC) met-HER2+ BCA (n = 125), T ↑ High HER3 expression was associated with worse PFS in initially metastatic HER2 + BCA
Bae et al. [26] IHC (DAK-H3-IC) HR-BCA (n = 886, HER2 + BCA n = 221) ↑ High HER3 expression was associated with poorer DFS in HER2 + BCA subgroup and poorer DFS and OS in TNBC
Czopek et al. [48] IHC (DAK-H3-IC) HER2+ BCA (n = 35) - No correlation between HER3 expression and DFS or OS
Lipton et al. [29] VeraTag assay met-HER2+ BCA (n = 89), T ↑ High HER3 expression was associated with shorter PFS in initially metastatic HER2 + BCA
Gori et al. [41] IHC (RTJ1) met-HER2+ BCA (n = 61), T - HER3 was not significantly associated with clinical outcome in initially metastatic HER2 + BCA
Han et al. [37] VeraTag assay met-HER2+ BCA (n = 50), T ↓ High HER3 expression was related to longer TTP in advanced HER2 + BCA
Larsen et al. [43] IHC (DAK-H3-IC) ER+ BCA (n = 1062) - HER3 expression did not shown any association to DFS
Chiu et al. [27] IHC (Ab-10 pAb) BCA (n = 3123) ↑ High HER3 expression was associated with decreased BCSS
Yonemori et al. [45] IHC (DAK-H3-IC) HER2+ BCA (n = 44), neoAdj.T - HER3 expression did not significantly correlate with pCR
Giltnane et al. [28] AQUA BCA (n = 550) ↑ High HER3 expression was associated with decreased survival
Haas et al. [42] IHC (SGP1) HER2- BCA (n = 171) - No prognostic value for HER3
Sassen et al. [50] IHC (5A12), FISH BCA (n = 173) - No prognostic value for HER3 expression, HER3 gene amplification was related to decreased DFS
Giuliani et al. [52] IHC (RTJ1) met-HER2+ BCA (n = 103), T - No prognostic value for HER3
Lee et al. [36] IHC (pAb) BCA (n = 378) ↓ High HER3 expression correlated with longer DFS
Bianchi et al. [53] IHC (RTJ1) BCA (n = 145) - No prognostic value for HER3 expression singly, but high co-expression of HER2/3/4 predicted worse prognosis
Fuchs et al. [34] IHC (C-17 pAb) BCA (n = 48) ↑ High HER3 expression singly and in co-expression with high HER1 and HER2 was associated with poor prognosis
Robinson et al. [32] IHC (polyclonal) met-HER2+ BCA (n = 104), T ↑ High HER3 expression was associated with worse OS
Wiseman et al. [33] IHC (2-18C9) BCA (n = 242) ↑ High HER3 expression independently and with high HER1 and/or HER2 was associated with decreased DSS
Abd El-Rehim et al. [15] IHC (RTJ1) BCA (n = 1499) - No prognostic value for HER3 singly, but in co-expression with high HER2 predicted unfavorable DFS and OS
Smith et al. [49] IHC met-HER2+ BCA (n = 77), T - No prognostic value for HER3
Bièche et al. [35] qRT-PCR BCA (n = 130) ↑ High HER3 mRNA was associated with shorten RFS
Witton et al. [30] IHC (H3.105.5) BCA (n = 220) ↑ High HER3 expression was associated with reduced BCSS survival
Suo et al. [47] IHC (sc-415), RT-PCR BCA (n = 100) - High HER3 expression was predictive for reduced DFS or BCSS only in co-overexpression with HER2 or HER1 + HER2
Pawlowski et al. [40] qRT-PCR BCA (n = 365) ↓ Elevated HER3 mRNA expression was associated with a better prognosis in terms of OS, but did not relate to RFS
Travis et al. [46] IHC (RTJ1) BCA (n = 346), met-BCA (n = 145) - No prognostic value for HER3 expression neither in primary nor metastatic breast cancer
Lemoine et al. [51] IHC (49.3 pAb) BCA (n = 195) - No demonstrable relationship between HER3 expression and survival
  1. Abbreviations: Adj.T = adjuvant trastuzumab therapy; BCA = primary breast cancer; BCSS = breast cancer-specific survival; DFS = disease-free survival; DSS = disease-specific survival; ER+ BCA = oestrogen receptor-positive breast cancer; HER2- BCA = HER2-negative breast cancer; HER2+ BCA = HER2-positive primary breast cancer; HR- BCA = hormone receptor-negative breast cancer; IHC = immunohistochemistry (antibody clone); met- = breast cancer diagnosed at advanced stage; MFS = metastasis-free survival; neoAdj.T = neoadjuvant trastuzumab therapy; n = number of patients being determined for HER3 status and followed for survival; OS = overall survival; pAb = polyclonal antibody; PFS = progression-free survival; pCR = pathologically complete response; qRT-PCR = quantitative reverse transcription polymerase chain reaction; RFS = recurrence-free survival; T = trastuzumab therapy after metastasis; TNBC = triple-negative breast cancer; TPD = trastuzumab, pertuzumab, docetaxel regimen; TTP = time to progression; ↑ = high HER3 mRNA or protein expression associated with worse clinical outcome; ↓ = low HER3 mRNA or protein expression associated with worse clinical outcome