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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

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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