Asian Pacific Journal of Cancer Prevention

Asian Pacific Organization for Cancer Prevention (아시아태평양암예방학회)
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Prognostic Significance of Human Epidermal Receptor (HER)-3 Immunohistochemical Expression in Patients with Metastatic Breast Cancer

  • Olmez, Omer Fatih (Department of Medical Oncology, Uludag University Medical School) ;
  • Evrensel, Turkkan (Department of Medical Oncology, Uludag University Medical School) ;
  • Cubukcu, Erdem (Department of Medical Oncology, Uludag University Medical School) ;
  • Ugras, Nesrin (Department of Pathology, Uludag University Medical School) ;
  • Avci, Nilufer (Department of Medical Oncology, Uludag University Medical School) ;
  • Canhoroz, Mustafa (Department of Medical Oncology, Uludag University Medical School) ;
  • Deligonul, Adem (Department of Medical Oncology, Uludag University Medical School) ;
  • Hartavi, Mustafa (Department of Medical Oncology, Uludag University Medical School) ;
  • Olmez, Fatma (Department of Obstetrics and Gynecology, Sevket Yilmaz Education and Research Hospital) ;
  • Cubukcu, Sinem (Department of Medical Oncology, Uludag University Medical School) ;
  • Tolunay, Sahsine (Department of Pathology, Uludag University Medical School) ;
  • Kurt, Ender (Department of Medical Oncology, Uludag University Medical School) ;
  • Kanat, Ozkan (Department of Medical Oncology, Uludag University Medical School) ;
  • Manavoglu, Osman (Department of Medical Oncology, Uludag University Medical School)
  • Published : 2013.07.30

Abstract

Background: Previous reports have shown that human epidermal receptor (HER)-3 overexpression may be associated with poor prognosis in patients with breast cancer, but results have been conflicting. In this study, we sought to investigate the prognostic significance of HER-3 immunohistochemical expression in patients with metastatic breast cancer. Methods: We retrospectively analyzed HER-3 immunohistochemical expression profiles in 45 paraffin-embedded specimens from patients who had been treated between 1996 and 2006 in the Department of Oncology of the Uludag University School of Medicine, Bursa, Turkey. Membranous or cytoplasmic dominant expression patterns of HER-3 were analyzed using the Rajkumar score and a cytoplasmic 4-point scoring system, respectively. Progression-free survival (PFS) and overall survival (OS) served as the main outcome measures. Results: The median PFS in the study participants was 9 months (interquartile range: 4.5-13 months), whereas the median OS was 20 months (interquartile range: 7.5-28 months). Categorization of the patient population according to HER-3 positive immunohistochemical expression did not reveal any statistically significant difference in terms of both PFS (p=0.70) and OS (p=0.81). The results of multivariable Cox regression analysis indicated that tumor size was the only independent predictor of PFS, whereas estrogen and progesterone receptor status was independently associated with OS. Conclusions: HER-3 immunohistochemical expression did not correlate with outcomes in Turkish patients with metastatic breast cancer. Although our results suggest that HER-3 expression in cancer specimens is not of prognostic significance, further prospective studies are warranted to confirm these results.

Keywords

Metastatic breast cancer;human epidermal receptor-3;immunohistochemistry;survival

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References

  1. Allred DC (2010). Issues and updates: evaluating estrogen receptor-alpha, progesterone receptor, and HER2 in breast cancer. Mod Pathol, 23, 52-9. https://doi.org/10.1038/modpathol.2010.55
  2. Amler LC (2010). HER3 mRNA as a predictive biomarker in anticancer therapy. Expert Opin Biol Ther, 10, 1343-55. https://doi.org/10.1517/14712598.2010.512003
  3. Bieche I, Onody P, Tozlu S, et al (2003). Prognostic value of ERBB family mRNA expression in breast carcinomas. Int J Cancer, 106, 758-65. https://doi.org/10.1002/ijc.11273
  4. Bloom HJ, Richardson WW (1957). Histological grading and prognosis in breast cancer; a study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer, 11, 359-77. https://doi.org/10.1038/bjc.1957.43
  5. Brufsky A (2010). Trastuzumab-based therapy for patients with HER2-positive breast cancer: from early scientific development to foundation of care. Am J Clin Oncol, 33, 186-95.
  6. Arslan C, Altundag K, Dizdar O (2011). Emerging drugs in metastatic breast cancer: an update. Expert Opin Emerg Drugs, 16, 647-67. https://doi.org/10.1517/14728214.2011.640672
  7. Chaudhri RA, Olivares-Navarrete R, Cuenca N, et al (2012). Membrane estrogen signaling enhances tumorigenesis and metastatic potential of breast cancer cells via estrogen receptor-${\alpha}36\;(ER{\alpha}36)$. J Biol Chem, 287, 7169-81. https://doi.org/10.1074/jbc.M111.292946
  8. Cortazar P, Justice R, Johnson J, et al (2012). US food and drug administration approval overview in metastatic breast cancer. J Clin Oncol, 30, 1705-11. https://doi.org/10.1200/JCO.2011.39.2613
  9. Eckhardt BL, Francis PA, Parker BS, Anderson RL (2012). Strategies for the discovery and development of therapies for metastatic breast cancer. Nat Rev Drug Discov, 11, 479-97. https://doi.org/10.1038/nrd2372
  10. Goel S, Chirgwin J, Francis P, et al (2011). Rational use of trastuzumab in metastatic and locally advanced breast cancer: implications of recent research. Breast, 20, 101-10. https://doi.org/10.1016/j.breast.2010.11.008
  11. Gullick WJ (1996). The c-erbB3/HER3 receptor in human cancer. Cancer Surv, 27, 339-49.
  12. Keating GM (2012). Pertuzumab: in the first-line treatment of HER2-positive metastatic breast cancer. Drugs, 72, 353-60. https://doi.org/10.2165/11209000-000000000-00000
  13. Koutras AK, Kalogeras KT, Dimopoulos MA, et al (2008). Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer. Br J Cancer, 99, 1775-85. https://doi.org/10.1038/sj.bjc.6604769
  14. Koutras AK, Fountzilas G, Kalogeras KT, et al (2010). The upgraded role of HER3 and HER4 receptors in breast cancer. Crit Rev Oncol Hematol, 74, 73-8. https://doi.org/10.1016/j.critrevonc.2009.04.011
  15. Lee Y, Cho S, Seo JH, et al (2007). Correlated expression of erbB-3 with hormone receptor expression and favourable clinical outcome in invasive ductal carcinomas of the breast. Am J Clin Pathol, 128, 1041-9. https://doi.org/10.1309/GA5VRFQFY5D0MVKD
  16. 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
  17. Lorusso P, Janne PA, Oliveira M, et al (2013). Phase I Study of U3-1287, a fully human anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Clin Cancer Res, 19, 3078-87 https://doi.org/10.1158/1078-0432.CCR-12-3051
  18. Lower EE, Glass EL, Bradley DA, Blau R, Heffelfinger S (2005). Impact of metastatic estrogen receptor and progesterone receptor status on survival. Breast Cancer Res Treat, 90, 65-70. https://doi.org/10.1007/s10549-004-2756-z
  19. Lyman GH, Burstein HJ, Buzdar AU, D'Agostino R, Ellis PA (2012). Making genuine progress against metastatic breast cancer. J Clin Oncol, 30, 3448-51. https://doi.org/10.1200/JCO.2012.43.6931
  20. Michaelson JS, Silverstein M, Sgroi D, et al (2003). The effect of tumor size and lymph node status on breast carcinoma lethality. Cancer, 98, 2133-43. https://doi.org/10.1002/cncr.11765
  21. Nanda R (2007). Targeting the human epidermal growth factor receptor 2 (HER2) in the treatment of breast cancer: recent advances and future directions. Rev Recent Clin Trials, 2, 111-6. https://doi.org/10.2174/157488707780599375
  22. Ocana A, Vera-Badillo F, Seruga B, et al (2013). HER3 overexpression and survival in solid tumors: a meta-analysis. J Natl Cancer Inst, 105, 266-73. https://doi.org/10.1093/jnci/djs501
  23. Orphanos G, Kountourakis P (2012). Targeting the HER2 receptor in metastatic breast cancer. Hematol Oncol Stem Cell Ther, 5, 127-37. https://doi.org/10.5144/1658-3876.2012.127
  24. Pawlowski V, Revillion F, Hebbar M, Hornez L, Peyrat JP (2000). 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, 6, 4217-25.
  25. Ravdin PM, Green S, Dorr TM, et al (1992). Prognostic significance of progesterone receptor levels in estrogen receptor-positive patients with metastatic breast cancer treated with tamoxifen: results of a prospective Southwest oncology group study. J Clin Oncol, 10, 1284-91.
  26. Sassen A, Rochon J, Wild P, et al (2008). Cytogenetic analysis of HER1/EGFR, HER2, HER3 and HER4 in 278 breast cancer patients. Breast Cancer Res, 10, 2.
  27. Stern DF (2008). ERBB3/HER3 and ERBB2/HER2 duet in mammary development and breast cancer. J Mammary Gland Biol Neoplasia, 13, 215-23. https://doi.org/10.1007/s10911-008-9083-7
  28. Sumida T, Itahana Y, Hamakawa H, Desprez PY (2004). Reduction of human metastatic breast cancer cell aggressiveness on introduction of either form a or B of the progesterone receptor and then treatment with progestins. Cancer Res, 64, 7886-92. https://doi.org/10.1158/0008-5472.CAN-04-1155
  29. Tafe LJ, Tsongalis GJ (2011). The human epidermal growth factor receptor 2 (HER2). Clin Chem Lab Med, 50, 23-30.
  30. Tanner B, Hasenclever D, Stern K, et al (2006). ErB-3 predicts survival in ovarian cancer. J Clin Oncol, 24, 4317-23. https://doi.org/10.1200/JCO.2005.04.8397
  31. Vaught DB, Stanford JC, Young C, et al (2012). HER3 is required for HER2-induced preneoplastic changes to the breast epithelium and tumor formation. Cancer Res, 72, 2672-82. https://doi.org/10.1158/0008-5472.CAN-11-3594
  32. Way TD, Lin JK (2005). Role of HER2/HER3 co-receptor in breast carcinogenesis. Future Oncol, 1, 841-9. https://doi.org/10.2217/14796694.1.6.841
  33. Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM (2003). Expression of the HER1-4 family of receptor tyrosine kinases in breast cancer. J Pathol, 200, 290-7. https://doi.org/10.1002/path.1370

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