Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

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

Authors: Satu Luhtala, Synnöve Staff, Anne Kallioniemi, Minna Tanner, Jorma Isola

Published in: BMC Cancer | Issue 1/2018

Login to get access

Abstract

Background

Human epidermal growth factor receptor HER3 (ErbB3), especially in association with its relative HER2 (ErbB2), is known as a key oncogene in breast tumour biology. Nonetheless, the prognostic relevance of HER3 remains controversial. NEDD4–1 and NRDP1 are signalling molecules closely related to the degradation of HER3 via ubiquitination. NEDD4–1 and NRDP1 have been reported to contribute to HER3-mediated signalling by regulating its localization and cell membrane retention. We studied correlations between HER3, NEDD4–1, and NRDP1 protein expression and their association with tumour histopathological characteristics and clinical outcomes.

Methods

The prevalence of immunohistochemically detectable expression profiles of HER3 (n = 177), NEDD4–1 (n = 145), and NRDP1 (n = 145) proteins was studied in primary breast carcinomas on archival formalin-fixed paraffin-embedded (FFPE) samples. Clinicopathological correlations were determined statistically using Pearson’s Chi-Square test. The Kaplan-Meier method, log-rank test (Mantel-Cox), and Cox regression analysis were utilized for survival analysis.

Results

HER3 protein was expressed in breast carcinomas without association with HER2 gene amplification status. Absence or low HER3 expression correlated with clinically aggressive features, such as triple-negative breast cancer (TNBC) phenotype, basal cell origin (cytokeratin 5/14 expression combined with ER negativity), large tumour size, and positive lymph node status. Low total HER3 expression was prognostic for shorter recurrence-free survival time in HER2-amplified breast cancer (p = 0.004, p = 0.020 in univariate and multivariate analyses, respectively). The majority (82.8%) of breast cancers demonstrated NEDD4–1 protein expression - while only a minor proportion (8.3%) of carcinomas expressed NRDP1. NEDD4–1 and NRDP1 expression were not associated with clinical outcomes in HER2-amplified breast cancer, irrespective of adjuvant trastuzumab therapy.

Conclusions

Low HER3 expression is suggested to be a valuable prognostic biomarker to predict recurrence in HER2-amplified breast cancer. Neither NEDD4–1 nor NRDP1 demonstrated relevance in prognostics or in the subclassification of HER2-amplified breast carcinomas.
Appendix
Available only for authorised users
Literature
1.
Zhang N, Chang Y, Rios A, An Z. HER3/ErbB3, an emerging cancer therapeutic target. Acta Biochim Biophys Sin Shanghai. 2016;48(1):39–48.PubMed
2.
Berger MB, Mendrola JM, Lemmon MA. ErbB3/HER3 does not homodimerize upon neuregulin binding at the cell surface. FEBS Lett. 2004;569(1–3):332–6.CrossRefPubMed
3.
Jura N, Shan Y, Cao X, Shaw DE, Kuriyan J. Structural analysis of the catalytically inactive kinase domain of the human EGF receptor 3. Proc Natl Acad Sci U S A. 2009;106(51):21608–13.PubMedCentralCrossRefPubMed
4.
Holbro T, Beerli RR, Maurer F, Koziczak M, Barbas CF 3rd, Hynes NE. The ErbB2/ErbB3 heterodimer functions as an oncogenic unit: ErbB2 requires ErbB3 to drive breast tumor cell proliferation. Proc Natl Acad Sci U S A. 2003;100(15):8933–8.PubMedCentralCrossRefPubMed
5.
Tzahar E, Waterman H, Chen X, Levkowitz G, Karunagaran D, Lavi S, et al. A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor/neuregulin and epidermal growth factor. Mol Cell Biol. 1996;16(10):5276–87.PubMedCentralCrossRefPubMed
6.
Hudelist G, Singer CF, Manavi M, Pischinger K, Kubista E, Czerwenka K. Co-expression of ErbB-family members in human breast cancer: her-2/neu is the preferred dimerization candidate in nodal-positive tumors. Breast Cancer Res Treat. 2003;80(3):353–61.CrossRefPubMed
7.
Hynes NE, MacDonald G. ErbB receptors and signaling pathways in cancer. Curr Opin Cell Biol. 2009;21(2):177–84.CrossRefPubMed
8.
Lee-Hoeflich ST, Crocker L, Yao E, Pham T, Munroe X, Hoeflich KP, et al. A central role for HER3 in HER2-amplified breast cancer: implications for targeted therapy. Cancer Res. 2008;68(14):5878–87.CrossRefPubMed
9.
Liu B, Ordonez-Ercan D, Fan Z, Huang X, Edgerton SM, Yang X, et al. Estrogenic promotion of ErbB2 tyrosine kinase activity in mammary tumor cells requires activation of ErbB3 signaling. Mol Cancer Res. 2009;7(11):1882–92.PubMed
10.
Vaught DB, Stanford JC, Young C, Hicks DJ, Wheeler F, Rinehart C, et al. HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation. Cancer Res. 2012;72(10):2672–82.PubMedCentralCrossRefPubMed
11.
Lyu H, Huang J, Edgerton SM, Thor AD, He Z, Liu B. Increased erbB3 promotes erbB2/neu-driven mammary tumor proliferation and co-targeting of erbB2/erbB3 receptors exhibits potent inhibitory effects on breast cancer cells. Int J Clin Exp Pathol. 2015;8(6):6143–56.PubMedCentralPubMed
12.
Siegel PM, Ryan ED, Cardiff RD, Muller WJ. Elevated expression of activated forms of Neu/ErbB-2 and ErbB-3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer. EMBO J. 1999;18(8):2149–64.PubMedCentralCrossRefPubMed
13.
Amin DN, Sergina N, Lim L, Goga A, Moasser MM. HER3 signalling is regulated through a multitude of redundant mechanisms in HER2-driven tumour cells. Biochem J. 2012;447(3):417–25.CrossRefPubMed
14.
Dey N, Williams C, Leyland-Jones B, De P. A critical role for HER3 in HER2-amplified and non-amplified breast cancers: function of a kinase-dead RTK. Am J Transl Res. 2015;7(4):733–50.PubMedCentralPubMed
15.
Abd El-Rehim DM, Pinder SE, Paish CE, Bell JA, Rampaul RS, Blamey RW, et al. Expression and co-expression of the members of the epidermal growth factor receptor (EGFR) family in invasive breast carcinoma. Br J Cancer. 2004;91(8):1532–42.PubMedCentralCrossRefPubMed
16.
Berghoff AS, Bartsch R, Preusser M, Ricken G, Steger GG, Bago-Horvath Z, et al. Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients. Breast. 2014;23(5):637–43.CrossRefPubMed
17.
Spears M, Taylor KJ, Munro AF, Cunningham CA, Mallon EA, Twelves CJ, et al. In situ detection of HER2:HER2 and HER2:HER3 protein-protein interactions demonstrates prognostic significance in early breast cancer. Breast Cancer Res Treat. 2012;132(2):463–70.CrossRefPubMed
18.
Barros FF, Abdel-Fatah TM, Moseley P, Nolan CC, Durham AC, Rakha EA, et al. Characterisation of HER heterodimers in breast cancer using in situ proximity ligation assay. Breast Cancer Res Treat. 2014;144(2):273–85.CrossRefPubMed
19.
Green AR, Barros FF, Abdel-Fatah TM, Moseley P, Nolan CC, Durham AC, et al. HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer. Breast Cancer Res Treat. 2014;145(1):33–44.PubMedCentralCrossRefPubMed
20.
Sak MM, Szymanska M, Bertelsen V, Hasmann M, Madshus IH, Stang E. Pertuzumab counteracts the inhibitory effect of ErbB2 on degradation of ErbB3. Carcinogenesis. 2013;34(9):2031–8.CrossRefPubMed
21.
Garrett JT, Sutton CR, Kuba MG, Cook RS, Arteaga CL. Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function. Clin Cancer Res. 2013;19(3):610–9.CrossRefPubMed
22.
Karamouzis MV, Dalagiorgou G, Georgopoulou U, Nonni A, Kontos M, Papavassiliou AG. HER-3 targeting alters the dimerization pattern of ErbB protein family members in breast carcinomas. Oncotarget. 2016;7(5):5576–97.CrossRefPubMed
23.
24.
Gaborit N, Lindzen M, Yarden Y. Emerging anti-cancer antibodies and combination therapies targeting HER3/ERBB3. Hum Vaccin Immunother. 2016;12(3):576–92.CrossRefPubMed
25.
Adamczyk A, Grela-Wojewoda A, Domagala-Haduch M, Ambicka A, Harazin-Lechowska A, Janecka A, et al. Proteins involved in HER2 Signalling pathway, their relations and influence on metastasis-free survival in HER2-positive breast Cancer patients treated with Trastuzumab in adjuvant setting. J Cancer. 2017;8(1):131–9.PubMedCentralCrossRefPubMed
26.
Bae SY, La Choi Y, Kim S, Kim M, Kim J, Jung SP, et al. HER3 status by immunohistochemistry is correlated with poor prognosis in hormone receptor-negative breast cancer patients. Breast Cancer Res Treat. 2013;139(3):741–50.CrossRefPubMed
27.
Chiu CG, Masoudi H, Leung S, Voduc DK, Gilks B, Huntsman DG, et al. HER-3 overexpression is prognostic of reduced breast cancer survival: a study of 4046 patients. Ann Surg. 2010;251(6):1107–16.CrossRefPubMed
28.
Giltnane JM, Moeder CB, Camp RL, Rimm DL. Quantitative multiplexed analysis of ErbB family coexpression for primary breast cancer prognosis in a large retrospective cohort. Cancer. 2009;115(11):2400–9.CrossRefPubMed
29.
Lipton A, Goodman L, Leitzel K, Cook J, Sperinde J, Haddad M, et al. HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of HER2-positive metastatic breast cancer. Breast Cancer Res Treat. 2013;141(1):43–53.PubMedCentralCrossRefPubMed
30.
Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM. Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003;200(3):290–7.CrossRefPubMed
31.
Park YH, Jung HA, Choi MK, Chang W, Choi YL, Do IG, et al. Role of HER3 expression and PTEN loss in patients with HER2-overexpressing metastatic breast cancer (MBC) who received taxane plus trastuzumab treatment. Br J Cancer. 2014;110(2):384–91.CrossRefPubMed
32.
Robinson AG, Turbin D, Thomson T, Yorida E, Ellard S, Bajdik C, et al. Molecular predictive factors in patients receiving trastuzumab-based chemotherapy for metastatic disease. Clin Breast Cancer. 2006;7(3):254–61.CrossRefPubMed
33.
Wiseman SM, Makretsov N, Nielsen TO, Gilks B, Yorida E, Cheang M, et al. Coexpression of the type 1 growth factor receptor family members HER-1, HER-2, and HER-3 has a synergistic negative prognostic effect on breast carcinoma survival. Cancer. 2005;103(9):1770–7.CrossRefPubMed
34.
Fuchs IB, Siemer I, Buhler H, Schmider A, Henrich W, Lichtenegger W, et al. Epidermal growth factor receptor changes during breast cancer metastasis. Anticancer Res. 2006;26(6B):4397–401.PubMed
35.
Bieche I, Onody P, Tozlu S, Driouch K, Vidaud M, Lidereau R. Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer. 2003;106(5):758–65.CrossRefPubMed
36.
Lee Y, Cho S, Seo JH, Shin BK, Kim HK, Kim I, et al. Correlated expression of erbB-3 with hormone receptor expression and favorable clinical outcome in invasive ductal carcinomas of the breast. Am J Clin Pathol. 2007;128(6):1041–9.CrossRefPubMed
37.
Han SW, Cha Y, Paquet A, Huang W, Weidler J, Lie Y, et al. Correlation of HER2, p95HER2 and HER3 expression and treatment outcome of lapatinib plus capecitabine in her2-positive metastatic breast cancer. PLoS One. 2012;7(7):e39943.PubMedCentralCrossRefPubMed
38.
Baselga J, Cortes J, Im SA, Clark E, Ross G, Kiermaier A, et al. Biomarker analyses in CLEOPATRA: a phase III, placebo-controlled study of pertuzumab in human epidermal growth factor receptor 2-positive, first-line metastatic breast cancer. J Clin Oncol. 2014;32(33):3753–61.CrossRefPubMed
39.
Koutras A, Kalogeras KT, Wirtz RM, Alexopoulou Z, Bobos M, Zagouri F, et al. Evaluation of the prognostic significance of HER family mRNA expression in high-risk early breast cancer: a Hellenic Cooperative Oncology Group (HeCOG) validation study. J Transl Med. 2015;13:171.PubMedCentralCrossRefPubMed
40.
Pawlowski V, Revillion F, Hebbar M, Hornez L, Peyrat JP. Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res. 2000;6(11):4217–25.PubMed
41.
Gori S, Foglietta J, Mameli MG, Stocchi L, Fenocchio D, Anastasi P, et al. HER-3 status by immunohistochemistry in HER-2-positive metastatic breast cancer patients treated with trastuzumab: correlation with clinical outcome. Tumori. 2012;98(1):39–44.CrossRefPubMed
42.
Haas S, Gevensleben H, Rabstein S, Harth V, Pesch B, Bruning T, et al. Expression of heregulin, phosphorylated HER-2, HER-3 and HER-4 in HER-2 negative breast cancers. Oncol Rep. 2009;21(2):299–304.PubMed
43.
Larsen MS, Bjerre K, Lykkesfeldt AE, Giobbie-Hurder A, Laenkholm AV, Henriksen KL, et al. Activated HER-receptors in predicting outcome of ER-positive breast cancer patients treated with adjuvant endocrine therapy. Breast. 2012;21(5):662–8.CrossRefPubMed
44.
Duchnowska R, Sperinde J, Czartoryska-Arlukowicz B, Mysliwiec P, Winslow J, Radecka B, et al. Predictive value of quantitative HER2, HER3 and p95HER2 levels in HER2-positive advanced breast cancer patients treated with lapatinib following progression on trastuzumab. Oncotarget. 2017;8(61):104149–59.PubMedCentralCrossRefPubMed
45.
Yonemori K, Tsuta K, Shimizu C, Hatanaka Y, Hirakawa A, Ono M, et al. Immunohistochemical expression of HER1, HER3, and HER4 in HER2-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy. J Surg Oncol. 2010;101(3):222–7.PubMed
46.
Travis A, Pinder SE, Robertson JF, Bell JA, Wencyk P, Gullick WJ, et al. C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators. Br J Cancer. 1996;74(2):229–33.PubMedCentralCrossRefPubMed
47.
Suo Z, Risberg B, Kalsson MG, Willman K, Tierens A, Skovlund E, et al. EGFR family expression in breast carcinomas. C-erbB-2 and c-erbB-4 receptors have different effects on survival. J Pathol. 2002;196(1):17–25.CrossRefPubMed
48.
Czopek J, Pawlega J, Fijorek K, Puskulluoglu M, Rozanowski P, Okon K. HER-3 expression in HER-2-amplified breast carcinoma. Contemp Oncol (Pozn). 2013;17(5):446–9.
49.
Smith BL, Chin D, Maltzman W, Crosby K, Hortobagyi GN, Bacus SS. The efficacy of Herceptin therapies is influenced by the expression of other erbB receptors, their ligands and the activation of downstream signalling proteins. Br J Cancer. 2004;91(6):1190–4.PubMedCentralCrossRefPubMed
50.
Sassen A, Rochon J, Wild P, Hartmann A, Hofstaedter F, Schwarz S, et al. Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res. 2008;10(1):R2.PubMedCentralCrossRefPubMed
51.
Lemoine NR, Barnes DM, Hollywood DP, Hughes CM, Smith P, Dublin E, et al. Expression of the ERBB3 gene product in breast cancer. Br J Cancer. 1992;66(6):1116–21.PubMedCentralCrossRefPubMed
52.
Giuliani R, Durbecq V, Di Leo A, Paesmans M, Larsimont D, Leroy JY, et al. Phosphorylated HER-2 tyrosine kinase and her-2/neu gene amplification as predictive factors of response to trastuzumab in patients with HER-2 overexpressing metastatic breast cancer (MBC). Eur J Cancer. 2007;43(4):725–35.CrossRefPubMed
53.
Bianchi S, Palli D, Falchetti M, Saieva C, Masala G, Mancini B, et al. ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study. J Cell Physiol. 2006;206(3):702–8.CrossRefPubMed
54.
Nishimura R, Toh U, Tanaka M, Saimura M, Okumura Y, Saito T, et al. Role of HER2-related biomarkers (HER2, p95HER2, HER3, PTEN, and PIK3CA) in the efficacy of Lapatinib plus Capecitabine in HER2-positive advanced breast Cancer refractory to Trastuzumab. Oncology. 2017;93(1):51–61.CrossRefPubMed
55.
Yang L, Li Y, Shen E, Cao F, Li L, Li X, et al. NRG1-dependent activation of HER3 induces primary resistance to trastuzumab in HER2-overexpressing breast cancer cells. Int J Oncol. 2017;51(5):1553–62.CrossRefPubMed
56.
Sato Y, Yashiro M, Takakura N. Heregulin induces resistance to lapatinib-mediated growth inhibition of HER2-amplified cancer cells. Cancer Sci. 2013;104(12):1618–25.CrossRefPubMedPubMedCentral
57.
Narayan M, Wilken JA, Harris LN, Baron AT, Kimbler KD, Maihle NJ. Trastuzumab-induced HER reprogramming in “resistant” breast carcinoma cells. Cancer Res. 2009;69(6):2191–4.CrossRefPubMed
58.
Choi BK, Fan X, Deng H, Zhang N, An Z. ERBB3 (HER3) is a key sensor in the regulation of ERBB-mediated signaling in both low and high ERBB2 (HER2) expressing cancer cells. Cancer Med. 2012;1(1):28–38.PubMedCentralCrossRefPubMed
59.
Choi MR, An CH, Chung YJ, Choi YJ, Yoo NJ, Lee SH. Mutational and expressional analysis of ERBB3 gene in common solid cancers. APMIS. 2014;122(12):1207–12.CrossRefPubMed
60.
Toomey S, Eustace AJ, Fay J, Sheehan KM, Carr A, Milewska M, et al. Impact of somatic PI3K pathway and ERBB family mutations on pathological complete response (pCR) in HER2-positive breast cancer patients who received neoadjuvant HER2-targeted therapies. Breast Cancer Res. 2017;19(1):87.PubMedCentralCrossRefPubMed
61.
Jaiswal BS, Kljavin NM, Stawiski EW, Chan E, Parikh C, Durinck S, et al. Oncogenic ERBB3 mutations in human cancers. Cancer Cell. 2013;23(5):603–17.CrossRefPubMed
62.
63.
Huang Z, Choi BK, Mujoo K, Fan X, Fa M, Mukherjee S, et al. The E3 ubiquitin ligase NEDD4 negatively regulates HER3/ErbB3 level and signaling. Oncogene. 2015;34(9):1105–15.CrossRefPubMed
64.
Cao Z, Wu X, Yen L, Sweeney C, Carraway KL 3rd. Neuregulin-induced ErbB3 downregulation is mediated by a protein stability cascade involving the E3 ubiquitin ligase Nrdp1. Mol Cell Biol. 2007;27(6):2180–8.PubMedCentralCrossRefPubMed
65.
Qiu XB, Goldberg AL. Nrdp1/FLRF is a ubiquitin ligase promoting ubiquitination and degradation of the epidermal growth factor receptor family member, ErbB3. Proc Natl Acad Sci U S A. 2002;99(23):14843–8.PubMedCentralCrossRefPubMed
66.
Fry WH, Simion C, Sweeney C, Carraway KL 3rd. Quantity control of the ErbB3 receptor tyrosine kinase at the endoplasmic reticulum. Mol Cell Biol. 2011;31(14):3009–18.PubMedCentralCrossRefPubMed
67.
Diamonti AJ, Guy PM, Ivanof C, Wong K, Sweeney C, Carraway KL 3rd. An RBCC protein implicated in maintenance of steady-state neuregulin receptor levels. Proc Natl Acad Sci U S A. 2002;99(5):2866–71.PubMedCentralCrossRefPubMed
68.
Lipkowitz S. The role of the ubiquitination-proteasome pathway in breast cancer: ubiquitin mediated degradation of growth factor receptors in the pathogenesis and treatment of cancer. Breast Cancer Res. 2003;5(1):8–15.CrossRefPubMed
69.
Zou X, Levy-Cohen G, Blank M. Molecular functions of NEDD4 E3 ubiquitin ligases in cancer. Biochim Biophys Acta. 2015;1856(1):91–106.PubMed
70.
Amodio N, Scrima M, Palaia L, Salman AN, Quintiero A, Franco R, et al. Oncogenic role of the E3 ubiquitin ligase NEDD4-1, a PTEN negative regulator, in non-small-cell lung carcinomas. Am J Pathol. 2010;177(5):2622–34.PubMedCentralCrossRefPubMed
71.
Sun A, Yu G, Dou X, Yan X, Yang W, Lin Q. Nedd4–1 is an exceptional prognostic biomarker for gastric cardia adenocarcinoma and functionally associated with metastasis. Mol Cancer. 2014;13:248.PubMedCentralCrossRefPubMed
72.
Huang ZJ, Zhu JJ, Yang XY, Biskup E. NEDD4 promotes cell growth and migration via PTEN/PI3K/AKT signaling in hepatocellular carcinoma. Oncol Lett. 2017;14(3):2649–56.PubMedCentralCrossRefPubMed
73.
Jung S, Li C, Jeong D, Lee S, Ohk J, Park M, et al. Oncogenic function of p34SEI-1 via NEDD41mediated PTEN ubiquitination/degradation and activation of the PI3K/AKT pathway. Int J Oncol. 2013;43(5):1587–95.CrossRefPubMed
74.
Chen Y, van de Vijver MJ, Hibshoosh H, Parsons R, Saal LH. PTEN and NEDD4 in human breast carcinoma. Pathol Oncol Res. 2016;22(1):41–7.CrossRefPubMed
75.
Yen L, Cao Z, Wu X, Ingalla ER, Baron C, Young LJ, et al. Loss of Nrdp1 enhances ErbB2/ErbB3-dependent breast tumor cell growth. Cancer Res. 2006;66(23):11279–86.CrossRefPubMed
76.
Jiao S, Liu W, Wu M, Peng C, Tang H, Xie X. Nrdp1 expression to predict clinical outcome and efficacy of adjuvant anthracyclines-based chemotherapy in breast cancer: a retrospective study. Cancer Biomark. 2015;15(2):115–23.CrossRefPubMed
77.
McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM, et al. REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer. 2005;93(4):387–91.PubMedCentralCrossRefPubMed
78.
Korhonen T, Huhtala H, Holli K. A comparison of the biological and clinical features of invasive lobular and ductal carcinomas of the breast. Breast Cancer Res Treat. 2004;85(1):23–9.CrossRefPubMed
79.
Korhonen T, Kuukasjarvi T, Huhtala H, Alarmo EL, Holli K, Kallioniemi A, et al. The impact of lobular and ductal breast cancer histology on the metastatic behavior and long term survival of breast cancer patients. Breast. 2013;22(6):1119–24.CrossRefPubMed
80.
Joensuu H, Kellokumpu-Lehtinen PL, Bono P, Alanko T, Kataja V, Asola R, et al. Adjuvant docetaxel or vinorelbine with or without trastuzumab for breast cancer. N Engl J Med. 2006;354(8):809–20.CrossRefPubMed
81.
Luhtala S, Staff S, Barok M, Tanner M, Isola J. Comparison of antibodies for immunohistochemistry-based detection of HER3 in breast Cancer. Appl Immunohistochem Mol Morphol. 2018;26(3):212–9.
82.
Koumakpayi IH, Diallo JS, Le Page C, Lessard L, Gleave M, Begin LR, et al. Expression and nuclear localization of ErbB3 in prostate cancer. Clin Cancer Res. 2006;12(9):2730–7.CrossRefPubMed
83.
Xu D, Wang H, Gardner C, Pan Z, Zhang PL, Zhang J, et al. The role of Nedd4-1 WW domains in binding and regulating human organic anion transporter 1. Am J Physiol Renal Physiol. 2016;311(2):F320–9.PubMedCentralCrossRefPubMed
84.
85.
86.
87.
Laakso M, Loman N, Borg A, Isola J. Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors. Mod Pathol. 2005;18(10):1321–8.CrossRefPubMed
88.
89.
90.
Collins D, Jacob W, Cejalvo JM, Ceppi M, James I, Hasmann M, et al. Direct estrogen receptor (ER) / HER family crosstalk mediating sensitivity to lumretuzumab and pertuzumab in ER+ breast cancer. PLoS One. 2017;12(5):e0177331.PubMedCentralCrossRefPubMed
91.
Takada K, Kashiwagi S, Goto W, Asano Y, Morisaki T, Fujita H, et al. Analysis of HER family (HER1-4) expression as a biomarker in combination therapy with Pertuzumab, Trastuzumab and docetaxel for advanced HER2-positive breast Cancer. Anticancer Res. 2018;38(4):2285–94.PubMed
92.
Kirouac DC, Du J, Lahdenranta J, Onsum MD, Nielsen UB, Schoeberl B, et al. HER2+ Cancer Cell Dependence on PI3K vs. MAPK Signaling Axes Is Determined by Expression of EGFR, ERBB3 and CDKN1B. PLoS Comput Biol. 2016;12(4):e1004827.PubMedCentralCrossRefPubMed
93.
Li Q, Zhang R, Yan H, Zhao P, Wu L, Wang H, et al. Prognostic significance of HER3 in patients with malignant solid tumors. Oncotarget. 2017;8(40):67140–51.PubMedCentralPubMed
94.
Ribelles N, Perez-Villa L, Jerez JM, Pajares B, Vicioso L, Jimenez B, et al. Pattern of recurrence of early breast cancer is different according to intrinsic subtype and proliferation index. Breast Cancer Res. 2013;15(5):R98.PubMedCentralCrossRefPubMed
95.
Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, et al. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res. 2014;16(4):R73.PubMedCentralCrossRefPubMed
96.
Denduluri N, Somerfield MR, Eisen A, Holloway JN, Hurria A, King TA, et al. Selection of optimal adjuvant chemotherapy regimens for human epidermal growth factor receptor 2 (HER2) -negative and adjuvant targeted therapy for HER2-positive breast cancers: an American Society of Clinical Oncology guideline adaptation of the Cancer Care Ontario clinical practice guideline. J Clin Oncol. 2016;34(20):2416–27.CrossRefPubMed
97.
Lambertini M, Ponde NF, Solinas C, de Azambuja E. Adjuvant trastuzumab: a 10-year overview of its benefit. Expert Rev Anticancer Ther. 2017;17(1):61–74.CrossRefPubMed
98.
Gyawali B, Niraula S. Duration of adjuvant trastuzumab in HER2 positive breast cancer: overall and disease free survival results from meta-analyses of randomized controlled trials. Cancer Treat Rev. 2017;60:18–23.CrossRefPubMed
99.
100.
Bertelsen V, Stang E. The mysterious ways of ErbB2/HER2 trafficking. Membranes (Basel). 2014;4(3):424–46.CrossRef
101.
Sak MM, Breen K, Ronning SB, Pedersen NM, Bertelsen V, Stang E, et al. The oncoprotein ErbB3 is endocytosed in the absence of added ligand in a clathrin-dependent manner. Carcinogenesis. 2012;33(5):1031–9.CrossRefPubMed
102.
103.
Reif R, Adawy A, Vartak N, Schroder J, Gunther G, Ghallab A, et al. Activated ErbB3 Translocates to the nucleus via Clathrin-independent endocytosis, which is associated with proliferating cells. J Biol Chem. 2016;291(8):3837–47.CrossRefPubMed
104.
Asp N, Pust S, Sandvig K. Flotillin depletion affects ErbB protein levels in different human breast cancer cells. Biochim Biophys Acta. 2014;1843(9):1987–96.CrossRefPubMed
105.
Asp N, Kvalvaag A, Sandvig K, Pust S. Regulation of ErbB2 localization and function in breast cancer cells by ERM proteins. Oncotarget. 2016;7(18):25443–60.PubMedCentralCrossRefPubMed
106.
Ghosh R, Narasanna A, Wang SE, Liu S, Chakrabarty A, Balko JM, et al. Trastuzumab has preferential activity against breast cancers driven by HER2 homodimers. Cancer Res. 2011;71(5):1871–82.PubMedCentralCrossRefPubMed
Metadata
Title
Clinicopathological and prognostic correlations of HER3 expression and its degradation regulators, NEDD4–1 and NRDP1, in primary breast cancer
Authors
Satu Luhtala
Synnöve Staff
Anne Kallioniemi
Minna Tanner
Jorma Isola
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4917-1

Other articles of this Issue 1/2018

BMC Cancer 1/2018 Go to the issue

Research article

Deep sequencing of human papillomavirus positive loco-regionally advanced oropharyngeal squamous cell carcinomas reveals novel mutational signature

Research article

Inhibition of autophagy sensitizes cancer cells to Photofrin-based photodynamic therapy

Research article

Cancer incidence and mortality rates and trends in Trinidad and Tobago

Debate

The curious case of Gαs gain-of-function in neoplasia

Research article

The prognostic significance of topoisomerase II alpha protein in early stage luminal breast cancer

Research article

Ezrin and E-cadherin expression profile in cervical cytology: a prognostic marker for tumor progression in cervical cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits