DOI QR코드

DOI QR Code

Recent Progress in HER2 Associated Breast Cancer

  • Wang, Wei-Jia (Department of Pathology, the First Affiliated Hospital of Nanchang University) ;
  • Lei, Yuan-Yuan (Department of Pathology, the First Affiliated Hospital of Nanchang University) ;
  • Mei, Jin-Hong (Department of Pathology, the First Affiliated Hospital of Nanchang University) ;
  • Wang, Chun-Liang (Department of Neurosurgery, the First Affiliated Hospital of Nanchang University)
  • Published : 2015.04.14

Abstract

Breast cancer is the most common cancer worldwide among women and the second most common cancer. Approximately 15-23% of breast cancers over-express human epidermal growth factor receptor2 (HER2), a 185-kDa transmembrane tyrosine kinase, which is mainly found at the cell surface of tumor cells. HER2-positive breast cancer, featuring amplification of HER2/neu and negative expression of ER and PR, has the three following characteristics: rapid tumor growth, lower survival rate, and better response to adjuvant therapies. Clinically, it is notable for its role in a pathogenesis that is associated with increased disease recurrence and acts as a worse prognosis. At the same time, it represents a good target for anti-cancer immunotherapy despite the prevalence of drug resistance. New treatments are a major topic of research, and a brighter future can be expected. This review discusses the role of HER2 in breast cancer, therapeutic modalities available and prognostic factors.

Keywords

References

  1. Aksamitiene E, Kiyatkin A, Kholodenko BN (2012). Cross-talk between mitogenic Ras/MAPK and survival PI3K/Akt pathways: a fine balance. Biochem Soc T, 40, 139-46. https://doi.org/10.1042/BST20110609
  2. Ali SM, Alpaugh RK, Buell JK, et al (2014). Antitumor response of an ERBB2 amplified inflammatory breast carcinoma with EGFR mutation to the EGFR-TKI erlotinib. Clin Breast Cancer, 14, 14-6. https://doi.org/10.1016/j.clbc.2013.09.010
  3. Alqaisi A, Chen L, Romond E, et al (2014). Impact of estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER2) co-expression on breast cancer disease characteristics: implications for tumor biology and research. Breast Cancer Res Treat, 148, 437-44. https://doi.org/10.1007/s10549-014-3145-x
  4. Arcila ME, Chaft JE, Nafa K, et al (2012). Prevalence, clinicopathologic associations and molecular spectrum of ERBB2 (HER2) tyrosine kinase mutations in lung adenocarcinomas. Clin Cancer Res, 18.
  5. Asp N, Pust S, Sandvig K (2014). Flotillin depletion affects ErbB protein levels in different human breast cancer cells. Biochim Biophys Acta, 1843, 1987-96. https://doi.org/10.1016/j.bbamcr.2014.04.013
  6. Auvinen P, Rilla K, Tumelius R, et al (2014). Hyaluronan synthases (HAS1-3) in stromal and malignant cells correlate with breast cancer grade and predict patient survival. Breast Cancer Res Treat, 143, 277-86. https://doi.org/10.1007/s10549-013-2804-7
  7. Bai WD, Ye XM, Zhang MY, et al (2014). MiR-200c suppresses TGF-beta signaling and counteracts trastuzumab resistance and metastasis by targeting ZNF217 and ZEB1 in breast cancer. Int J Cancer, 135, 1356-68. https://doi.org/10.1002/ijc.28782
  8. Ballinger TJ, Sanders ME, Abramson VG (2014). Current HER2 testing recommendations and clinical relevance as a predictor of response to targeted therapy. Clin Breast Cancer.
  9. Barroso-Sousa R, Santana IA, Testa L, et al (2013). Biological therapies in breast cancer: common toxicities and management strategies. Breast, 22, 1009-18. https://doi.org/10.1016/j.breast.2013.09.009
  10. Ben-Kasus T, Schechter B, Lavi S, et al (2009). Persistent elimination of ErbB-2/HER2-overexpressing tumors using combinations of monoclonal antibodies: Relevance of receptor endocytosis. Proc Natl Acad Sci USA, 106, 3294-9. https://doi.org/10.1073/pnas.0812059106
  11. Bessadottir M, Skuladottir EA, Gowan S, et al (2014). Effects of anti-proliferative lichen metabolite, protolichesterinic acid on fatty acid synthase, cell signalling and drug response in breast cancer cells. Phytomedicine, 21, 1717-24. https://doi.org/10.1016/j.phymed.2014.08.006
  12. Bilous M, Morey AL, Armes JE, et al (2012). Assessing HER2 amplification in breast cancer: findings from the Australian In situ hybridization program. Breast Cancer Res Treat, 134, 617-24. https://doi.org/10.1007/s10549-012-2093-6
  13. Blok EJ, Kuppen PJ, van Leeuwen JE, et al (2013). Cytoplasmic overexpression of HER2: a key factor in colorectal cancer. Clin Med Insights Oncol, 7, 41-51.
  14. Boku N (2014). HER2-positive gastric cancer. Gastric Cancer, 17, 1-12. https://doi.org/10.1007/s10120-013-0252-z
  15. Boulbes DR, Arold ST, Chauhan GB, et al (2014). HER family kinase domain mutations promote tumor progression and can predict response to treatment in human breast cancer. Mol Oncol, 9, 586-600.
  16. Brady SW, Zhang J, Seok D, et al (2014). Enhanced PI3K p110alpha signaling confers acquired lapatinib resistance that can be effectively reversed by a p110alpha-selective PI3K inhibitor. Mol Cancer Ther, 13, 60-70.
  17. Cao J, Jin Y, Li W, et al (2013). DNA vaccines targeting the encoded antigens to dendritic cells induce potent antitumor immunity in mice. BMC Immunol, 14, 39. https://doi.org/10.1186/1471-2172-14-39
  18. Chen L, Bourguignon LY (2014). Hyaluronan-CD44 interaction promotes c-Jun signaling and miRNA21 expression leading to Bcl-2 expression and chemoresistance in breast cancer cells. Mol Cancer, 13, 52. https://doi.org/10.1186/1476-4598-13-52
  19. Chmielecki J, Ross JS, Wang K, et al (2014). Oncogenic alterations in ERBB2/HER2 represent potential therapeutic targets across tumors from diverse anatomic sites of origin. Oncologist.
  20. Cruz GI, Martinez ME, Natarajan L, et al (2013). Hypothesized role of pregnancy hormones on HER2+ breast tumor development. Breast Cancer Res Treat, 137, 237-46. https://doi.org/10.1007/s10549-012-2313-0
  21. De Luca A, Maiello MR, D'Alessio A, et al (2012). The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches. Expert Opin Ther Targets, 16, 17-27.
  22. Delea TE, Hawkes C, Amonkar MM, et al (2013). Cost-effectiveness of lapatinib plus letrozole in post-menopausal women with hormone receptor-and HER2-positive metastatic breast cancer. Breast Care (Basel), 8, 429-37. https://doi.org/10.1159/000357316
  23. Dittrich A, Gautrey H, Browell D, et al (2014). The HER2 signaling network in breast cancer-like a spider in its web. J Mammary Gland Biol Neoplasia, [Epub ahead of print].
  24. Dong Y, Van Tine BA, Oyama T, et al (2014). Taspase1 cleaves MLL1 to activate cyclin E for HER2/neu breast tumorigenesis. Cell Res, 24, 1354-66. https://doi.org/10.1038/cr.2014.129
  25. Duchnowska R, Jassem J, Goswami CP, et al (2015). Predicting early brain metastases based on clinicopathological factors and gene expression analysis in advanced HER2-positive breast cancer patients. J Neurooncol, 122, 205-16. https://doi.org/10.1007/s11060-014-1704-y
  26. Ebi H, Costa C, Faber AC, et al (2013). PI3K regulates MEK/ERK signaling in breast cancer via the rac-GEF, P-Rex1. Proc Natl Acad Sci U S A, 110, 21124-9. https://doi.org/10.1073/pnas.1314124110
  27. Fountzilas G, Valavanis C, Kotoula V, et al (2012). HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy. J Transl Med, 10, 10. https://doi.org/10.1186/1479-5876-10-10
  28. Freudenberg JA, Wang Q, Katsumata M, et al (2009). The role of HER2 in early breast cancer metastasis and the origins of resistance to HER2-targeted therapies. Exp Mol Pathol, 87, 1-11. https://doi.org/10.1016/j.yexmp.2009.05.001
  29. Garrett J, Sutton C, Kuba M, et al (2013). Dual blockade of HER2 in HER2-overexpressing tumor cells does not completely eliminate HER3 function.Clin Cancer Res, 19, 610-9. https://doi.org/10.1158/1078-0432.CCR-12-2024
  30. Gennari R, Menard S, Fagnoni F, et al (2004). Pilot study of the mechanism of action ofpreoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res, 10, 5650-5. https://doi.org/10.1158/1078-0432.CCR-04-0225
  31. Gorbatenko A, Olesen CW, Morup N, et al (2014). ErbB2 upregulates the Na+, HCO3 (-)-cotransporter NBCn1/SLC4A7 in human breast cancer cells via Akt, ERK, Src, and Kruppel-like factor 4. Faseb J, 28, 350-63. https://doi.org/10.1096/fj.13-233288
  32. Green AR, Barros FF, Abdel-Fatah TM, et al (2014). HER2/HER3 heterodimers and p21 expression are capable of predicting adjuvant trastuzumab response in HER2+ breast cancer. Breast Cancer Res Treat, 145, 33-44. https://doi.org/10.1007/s10549-014-2925-7
  33. Hosonaga M, Arima Y, Sugihara E, et al (2014). Expression of CD24 is associated with HER2 expression and supports HER2-Akt signaling in HER2-positive breast cancer cells. Cancer Sci, 105, 779-87. https://doi.org/10.1111/cas.12427
  34. Huang L, Chen T, Chen C, et al (2013). Prognostic and predictive value of Phospho-p44/42 and pAKT in HER2-positive locally advanced breast cancer patients treated with anthracycline-based neoadjuvant chemotherapy. World J Surg Oncol, 11, 307. https://doi.org/10.1186/1477-7819-11-307
  35. Huang W, Wu QD, Zhang M, et al (2015). Novel Hsp90 inhibitor FW-04-806 displays potent antitumor effects in HER2-positive breast cancer cells as a single agent or in combination with lapatinib. Cancer Lett, 356, 862-71. https://doi.org/10.1016/j.canlet.2014.10.040
  36. Huang W, Ye M, Zhang LR, et al (2014). FW-04-806 inhibits proliferation and induces apoptosis in human breast cancer cells by binding to N-terminus of Hsp90 and disrupting Hsp90-Cdc37 complex formation. Mol Cancer, 13, 150. https://doi.org/10.1186/1476-4598-13-150
  37. Hudis C, Swanton C, Janjigian YY, et al (2013). A phase 1 study evaluating the combination of an allosteric AKT inhibitor (MK-2206) and trastuzumab in patients with HER2-positive solid tumors. Breast Cancer Res, 15, 110. https://doi.org/10.1186/bcr3577
  38. Huynh FC, Jones FE (2014). MicroRNA-7 Inhibits multiple oncogenic pathways to suppress HER2Delta16 mediated breast tumorigenesis and reverse trastuzumab resistance. PLoS One, 9, 114419. https://doi.org/10.1371/journal.pone.0114419
  39. Imami K, Sugiyama N, Imamura H, et al (2012). Temporal profiling of lapatinib-suppressed phosphorylation signals in EGFR/HER2 pathways. Mol Cell Proteomics, 11, 1741-57. https://doi.org/10.1074/mcp.M112.019919
  40. Iqbal N, Iqbal N (2014). Human epidermal growth factor receptor 2 (HER2) in Cancers: overexpression and therapeutic implications. Mol Biol Int, 2014, 852748.
  41. Kanthala S, Gauthier T, Satyanarayanajois S (2014). Structure-activity relationships of peptidomimetics that inhibit PPI of HER2-HER3. Biopolymers, 101, 693-702. https://doi.org/10.1002/bip.22441
  42. Kawajiri H, Takashima T, Kashiwagi S, et al (2015). Pertuzumab in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Expert Rev Anticancer Ther, 15, 17-26. https://doi.org/10.1586/14737140.2015.992418
  43. Khan S, Shukla S, Sinha S, et al (2015). Centchroman suppresses breast cancer metastasis by reversing epithelial-mesenchymal transition via downregulation of HER2/ERK1/2/MMP-9 signaling. Int J Biochem Cell Biol, 58, 1-16. https://doi.org/10.1016/j.biocel.2014.10.028
  44. Kumler I, Tuxen MK, Nielsen DL (2014). A systematic review of dual targeting in HER2-positive breast cancer. Cancer Treat Rev, 40, 259-70. https://doi.org/10.1016/j.ctrv.2013.09.002
  45. Kurata T, Tsurutani J, Fujisaka Y, et al (2014). Inhibition of EGFR, HER2 and HER3 signaling with AZD8931 alone and in combination with paclitaxel: phase i study in Japanese patients with advanced solid malignancies and advanced breast cancer. Invest New Drugs, 32, 946-54. https://doi.org/10.1007/s10637-014-0112-7
  46. Ladjemi MZ, Jacot W, Chardes T, et al (2010). Anti-HER2 vaccines: new prospects for breast cancer therapy. Cancer Immunol Immunother, 59, 1295-312. https://doi.org/10.1007/s00262-010-0869-2
  47. Lanning RM, Morrow M, Riaz N, et al (2015). The effect of adjuvant trastuzumab on locoregional recurrence of human epidermal growth factor receptor 2-positive breast cancer treated with mastectomy. Ann Surg Oncol.
  48. Lapin V, Shirdel EA, Wei X, et al (2014). Kinome-wide screening of HER2+ breast cancer cells for molecules that mediate cell proliferation or sensitize cells to trastuzumab therapy. Oncogenesis, 3, 133. https://doi.org/10.1038/oncsis.2014.45
  49. Lee HJ, Seo AN, Kim EJ, et al (2015). Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer. Br J Cancer, 112, 103-11. https://doi.org/10.1038/bjc.2014.556
  50. Lee MY, Marina M, King JL, et al (2014). Differential expression of centrosome regulators in Her2+ breast cancer cells versus non-tumorigenic MCF10A cells. Cell Div, 9, 3. https://doi.org/10.1186/1747-1028-9-3
  51. Leivonen SK, Sahlberg KK, Makela R, et al (2014). High-throughput screens identify microRNAs essential for HER2 positive breast cancer cell growth. Mol Oncol, 8, 93-104. https://doi.org/10.1016/j.molonc.2013.10.001
  52. Li JW, Mo M, Yu KD, et al (2014). ER-Poor and HER2-positive: a potential subtype of breast cancer to avoid axillary dissection in node positive patients after neoadjuvant chemotrastuzumab therapy. PLoS One, 9, 114646. https://doi.org/10.1371/journal.pone.0114646
  53. Liu Y, Liu Q, Wang T, et al (2013). Circulating tumor cells in HER2-positive metastatic breast cancer patients: a valuable prognostic and predictive biomarker. BMC Cancer, 13, 202. https://doi.org/10.1186/1471-2407-13-202
  54. Luo TY, Cheng PC, Chiang PF, et al (2015). (188) Re-HYNIC-trastuzumab enhances the effect of apoptosis induced by trastuzumab in HER2-overexpressing breast cancer cells. Ann Nucl Med, 29, 52-62. https://doi.org/10.1007/s12149-014-0908-8
  55. Luu T, Chung C, Somlo G (2011). Combining emerging agents in advanced breast cancer. Oncologist, 16, 760-71. https://doi.org/10.1634/theoncologist.2010-0345
  56. Mehta A, Tripathy D (2014). Co-targeting estrogen receptor and HER2 pathways in breast cancer. Breast, 23, 2-9. https://doi.org/10.1016/j.breast.2013.09.006
  57. Menendez JA, Vazquez-Martin A, Garcia-Villalba R, et al (2008). tabAnti-HER2 (erbB-2) oncogene effects of phenolic compounds directly isolated from commercial Extra-Virgin Olive Oil (EVOO). BMC Cancer, 8, 377. https://doi.org/10.1186/1471-2407-8-377
  58. Mirmalek SA, Hajilou M, Salimi Tabatabaee SA, et al (2014). Prevalence of HER-2 and hormone receptors and P53 mutations in the pathologic specimens of breast cancer patients. Int J Breast Cancer, 2014, 564308.
  59. Mittendorf EA, Liu Y, Tucker SL, et al (2010). A novel interaction between HER2/neu and cyclin E in breast cancer. Oncogene, 29, 3896-907. https://doi.org/10.1038/onc.2010.151
  60. Mohd Sharial MSN, Crown J, Hennessy BT (2012). Overcoming resistance and restoring sensitivity to HER2-targeted therapies in breast cancer. Ann Oncol, 23, 3007-16. https://doi.org/10.1093/annonc/mds200
  61. Moody SE, Schinzel AC, Singh S, et al (2014). PRKACA mediates resistance to HER2-targeted therapy in breast cancer cells and restores anti-apoptotic signaling. Oncogene, [Epub ahead of print].
  62. Morrison G, Fu X, Shea M, et al (2014). Therapeutic potential of the dual EGFR/HER2 inhibitor AZD8931 in circumventing endocrine resistance. Breast Cancer Res Treat, 144, 263-72. https://doi.org/10.1007/s10549-014-2878-x
  63. Mortimer JE, Bading JR, Colcher DM, et al (2014). Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET. J Nucl Med, 55, 23-9. https://doi.org/10.2967/jnumed.113.122630
  64. Muendlein A, Hubalek M, Geller-Rhomberg S, et al (2014). Significant survival impact of MACC1 polymorphisms in HER2 positive breast cancer patients. Eur J Cancer, 50, 2134-41. https://doi.org/10.1016/j.ejca.2014.05.007
  65. Nahta R (2012). Molecular mechanisms of trastuzumab-based treatment in HER2-overexpressing breast cancer. ISRN Oncol, 2012.
  66. Nair R, Roden DL, Teo WS, et al (2014). c-Myc and Her2 cooperate to drive a stem-like phenotype with poor prognosis in breast cancer. Oncogene, 33, 3992-4002. https://doi.org/10.1038/onc.2013.368
  67. Nam S, Chang HR, Jung HR, et al (2015). A pathway-based approach for identifying biomarkers of tumor progression to trastuzumab-resistant breast cancer. Cancer Lett, 356, 880-90. https://doi.org/10.1016/j.canlet.2014.10.038
  68. Nielsen BS, Balslev E, Poulsen TS, et al (2014). miR-21 expression in cancer cells may not predict resistance to adjuvant trastuzumab in primary breast cancer. Front Oncol, 4, 207.
  69. Omenn GS, Guan Y, Menon R (2014). A new class of protein cancer biomarker candidates: differentially expressed splice variants of ERBB2 (HER2/neu) and ERBB1 (EGFR) in breast cancer cell lines. J Proteomics, 107, 103-12. https://doi.org/10.1016/j.jprot.2014.04.012
  70. Pandey JP, Kistner-Griffin E, Black L, et al (2014). IGKC and FcgammaR genotypes and humoral immunity to HER2 in breast cancer. Immunobiol, 219, 113-7. https://doi.org/10.1016/j.imbio.2013.08.005
  71. Pang B, Sun SP, Gao L, et al (2014). A single nucleotide polymorphism in PIK3CA gene is inversely associated with P53 protein expression in breast cancer. Med Oncol, 31, 30. https://doi.org/10.1007/s12032-014-0030-8
  72. Pazhoomand R, Keyhani E, Banan M, et al (2013). Detection of HER2 status in breast cancer: comparison of current methods with MLPA and real-time RT-PCR. Asian Pac J Cancer Prev, 14, 7621-8. https://doi.org/10.7314/APJCP.2013.14.12.7621
  73. Prat A, Carey LA, Adamo B, et al (2014). Molecular features and survival outcomes of the intrinsic subtypes within HER2-positive breast cancer. J Natl Cancer Inst, 106.
  74. Rakha EA, Pinder SE, Bartlett JM, et al (2015). Updated UK recommendations for HER2 assessment in breast cancer. J Clin Pathol, 68, 93-9 https://doi.org/10.1136/jclinpath-2014-202571
  75. Rimawi MF, Aleixo SB, Rozas AA, et al (2014). A neoadjuvant, randomized, open-label phase II trial of afatinib versus trastuzumab versus lapatinib in patients with locally advanced HER2-positive breast cancer. Clin Breast Cancer.
  76. Rouanet P, Roger P, Rousseau E, et al (2014). HER2 overexpression a major risk factor for recurrence in pT1a-bN0M0 breast cancer: results from a French regional cohort. Cancer Med, 3, 134-42. https://doi.org/10.1002/cam4.167
  77. Rugo HS, Brufsky AM, Ulcickas Yood M, et al (2013). Racial disparities in treatment patterns and clinical outcomes in patients with HER2-positive metastatic breast cancer. Breast Cancer Res Treat, 141, 461-70. https://doi.org/10.1007/s10549-013-2697-5
  78. Scaltriti M, Nuciforo P, Bradbury I, et al (2014). High HER2 expression correlates with response to the combination of lapatinib and trastuzumab. Clin Cancer Res, 21, 569-76.
  79. Schroeder RL, Stevens CL, Sridhar J (2014). Small molecule tyrosine kinase inhibitors of ErbB2/HER2/Neu in the treatment of aggressive breast cancer. Molecules, 19, 15196-212. https://doi.org/10.3390/molecules190915196
  80. Sclafani F, Roy A, Cunningham D, et al (2013). HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab. Ann Oncol, 24, 3123-8. https://doi.org/10.1093/annonc/mdt408
  81. Segovia-Mendoza M, Diaz L, Gonzalez-Gonzalez ME, et al (2015). Calcitriol and its analogues enhance the antiproliferative activity of gefitinib in breast cancer cells. J Steroid Biochem Mol Biol, 148, 122-31 https://doi.org/10.1016/j.jsbmb.2014.12.006
  82. Shinde AM, Zhai J, Yu KW, et al (2015). Pathologic complete response rates in triple-negative, HER2-positive, and hormone receptor-positive breast cancers after anthracycline-free neoadjuvant chemotherapy with carboplatin and paclitaxel with or without trastuzumab. Breast, 24, 18-23. https://doi.org/10.1016/j.breast.2014.10.008
  83. Spicer J, Baird R, Suder A, et al (2015). Phase 1 dose-escalation study of S-222611, an oral reversible dual tyrosine kinase inhibitor of EGFR and HER2, in patients with solid tumours. Eur J Cancer, 51, 137-45. https://doi.org/10.1016/j.ejca.2014.11.003
  84. Sueta A, Yamamoto Y, Yamamoto-Ibusuki M, et al (2014). An integrative analysis of PIK3CA mutation, PTEN, and INPP4B expression in terms of trastuzumab efficacy in HER2-positive breast cancer. PLoS One, 9, 116054. https://doi.org/10.1371/journal.pone.0116054
  85. Tagliabue E, Campiglio M (2014). "Omics" and Immunologic approaches to optimizing cure rates in HER2-positive breast carcinomas. Front Oncol, 4, 334.
  86. Takada M, Higuchi T, Tozuka K, et al (2013). Alterations of the genes involved in the PI3K and estrogen-receptor pathways influence outcome in human epidermal growth factor receptor 2-positive and hormone receptor-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy. BMC Cancer, 13, 241. https://doi.org/10.1186/1471-2407-13-241
  87. Tolaney SM, Barry WT, Dang CT, et al (2015). Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med, 372, 134-41. https://doi.org/10.1056/NEJMoa1406281
  88. Victorino VJ, Campos FC, Herrera AC, et al (2014). Overexpression of HER-2/neu protein attenuates the oxidative systemic profile in women diagnosed with breast cancer. Tumour Biol, 35, 3025-34. https://doi.org/10.1007/s13277-013-1391-x
  89. Wu Y, Mohamed H, Chillar R, et al (2008). Clinical significance of Akt and HER2/neu overexpression in African-American and Latina women with breast cancer. Breast Cancer Res, 10, 3.
  90. Xia W, Petricoin EF, Zhao S, et al (2013). An heregulin-EGFR-HER3 autocrine signaling axis can mediate acquired lapatinib resistance in HER2+ breast cancer models. Breast Cancer Res, 15, 85. https://doi.org/10.1186/bcr3480
  91. Xu C, Chen H, Wang X, et al (2014). S100A14, a member of the EF-hand calcium-binding proteins, is overexpressed in breast cancer and acts as a modulator of HER2 signaling. J Biol Chem, 289, 827-37. https://doi.org/10.1074/jbc.M113.469718
  92. Yan Y, Hein AL, Greer PM, et al (2014). A novel function of HER2/Neu in the activation of G2/M checkpoint in response to gamma-irradiation. Oncogene, 0. [Epub ahead of print]
  93. Yeh ES, Abt MA, Hill EG (2014). Regulation of cell survival by HUNK mediates breast cancer resistance to HER2 inhibitors. Breast Cancer Res Treat, 149, 91-8
  94. Yu AF, Yadav NU, Lung BY, et al (2015). Trastuzumab interruption and treatment-induced cardiotoxicity in early HER2-positive breast cancer. Breast Cancer Res Treat, 149, 489-95. https://doi.org/10.1007/s10549-014-3253-7
  95. Zang F, Wei X, Leng X, et al (2014). C-FLIP (L) contributes to TRAIL resistance in HER2-positive breast cancer. Biochem Biophys Res Commun, 450, 267-73. https://doi.org/10.1016/j.bbrc.2014.05.106
  96. Zhang S, Huang WC, Li P, et al (2011). Combating trastuzumab resistance by targeting SRC, a common node downstream of multiple resistance pathways. Nat Med, 17, 461-9. https://doi.org/10.1038/nm.2309
  97. Zhu ZL, Zhang J, Chen ML, et al (2013). Efficacy and safety of trastuzumab added to standard treatments for HER2-positive metastatic breast cancer patients. Asian Pac J Cancer Prev, 14, 7111-6. https://doi.org/10.7314/APJCP.2013.14.12.7111

Cited by

  1. Differences in Prognostic Factors between Early and Late Recurrence Breast Cancers vol.16, pp.15, 2015, https://doi.org/10.7314/APJCP.2015.16.15.6575
  2. Functional and therapeutic significance of protein kinase D enzymes in invasive breast cancer vol.72, pp.22, 2015, https://doi.org/10.1007/s00018-015-2011-2
  3. Relationship between erb-B2 mRNA Expression in Blood and Tissue of Invasive Ductal Carcinoma Breast Cancer Patients and Clinicopathological Characteristics of the Tumors vol.17, pp.1, 2016, https://doi.org/10.7314/APJCP.2016.17.1.249
  4. Metabolic Portraits of Breast Cancer by HR MAS MR Spectroscopy of Intact Tissue Samples vol.7, pp.2, 2017, https://doi.org/10.3390/metabo7020018
  5. Role of RUNX2 in Breast Carcinogenesis vol.16, pp.9, 2015, https://doi.org/10.3390/ijms160920969