Immunohistochemistry Subtypes (ER/PR/HER) of Breast Cancer: Where Do We Stand in the West of Saudi Arabia?

  • Khabaz, Mohamad Nidal (Department of Pathology, Faculty of Medicine, Rabigh Branch, King Abdulaziz University)
  • Published : 2014.10.23


In Saudi Arabia, cancer of breast is ranked the most frequent neoplasm and second source of cancer death in the female population. Breast cancer (BC) fast diagnosis, prognosis and medication management necessitate, these days, immunohistochemistry (IHC) assessment of hormone receptors and HER2 expression profile. The present report defines the IHC profile of ER, PR and HER2 in Saudi female breast neoplasms of ductal and lobular types and associations ER, PR and HER2 expression patterns with various clinicopathological factors (age, type of tumor, size, laterality, histological grade, and involvement of axillaries lymph nodes). Ninety nine cases of breast tumors were recruited from the pathology department archive of King Abdulaziz University Hospital, Kingdom of Saudi Arabia. ER, PR and HER2 expression was assessed using IHC staining. Ductal carcinomas with a variety of histological grades constituted 88 (88.8%) of total cases. Seventy four (77.8%), 59 (62.1%), and 35 (36.8%) of ductal carcinomas showed positive staining for ER, PR and HER2, in that order. Remaining breast cancer cases were four (4%) lobular carcinomas and two (2%) mixed form of ductal and lobular types, which were ER+, PR+, and HER2-. Breast cancer expression pattern of ER, PR and HER2 in Saudi female is different from that of Tunisian and Jordanian female populations and closer to the expression pattern of Egyptian, Lebanese, Iraqi and western country females. Furthermore, the present study found two IHC patterns of breast cancer ER+/PR-/HER2+ (5%) and ER+/PR-/HER2- (11.1%), which had not been reported in other Arabic studies. Thus the rates of IHC expression patterns in breast cancer show some variation among Arabic female populations.


Breast cancer;ER;HER2;PR;immunohistochemistry;Saudi Arabia females


  1. Allred DC, Harvey JM, Berardo M, Clark GM (1998). Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol, 2, 155-68.
  2. Aiad HA, Wahed MM, Asaad NY, El-Tahmody M, Elhosary E (2014). Immunohistochemical expression of GPR30 in breast carcinoma of Egyptian patients: an association with immunohistochemical subtypes. APMIS, (Epub ahead of print).
  3. Al-Eid HS, Garcia AD (2012). Cancer incidence report saudi arabia 2009. Saudi Cancer Registry, Ministry of Health, Kingdom of Saudi Arabia.
  4. Allred DC, Carlson RW, Berry DA, et al (2009). NCCN task force report: estrogen receptor and progesterone receptor testing in breast cancer by immunohistochemistry. J Natl Compr Canc Netw, 6, 1-21.
  5. Ambroise M, Ghosh M, Mallikarjuna VS, Kurian A (2011). Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev, 12, 625-9.
  6. Anderson E, Clarke RB, Howell A (1998) Estrogen responsiveness and control of normal human breast proliferation. J Mammary Gland Biol Neoplasia, 1, 23-35.
  7. Aryandono T, Harijadi, Soeripto (2006). Hormone receptor status of operable breast cancers in Indonesia: correlation with other prognostic factors and survival. Asian Pac J Cancer Prev, 7, 321-4.
  8. Azizun-Nisa, Bhurgri Y, Raza F, Kayani N (2008). Comparison of ER, PR and HER-2/neu (C-erb B 2) reactivity pattern with histologic grade, tumor size and lymph node status in breast cancer. Asian Pac J Cancer Prev, 9, 553-6.
  9. Ban KA, Godellas CV (2014). Epidemiology of breast cancer. Surg Oncol Clin N Am, 3, 409-22.
  10. Barnes DM, Hanby AM (2001). Oestrogen and progesterone receptors in breast cancer: past, present and future. Histopathology, 3, 271-4.
  11. Chow LW, Ho P (2000). Hormonal receptor determination of 1,052 Chinese breast cancers. J Surg Oncol, 3, 172-5.
  12. Bartlett JM, Rea D, Rimm DL (2011). Quantification of hormone receptors to guide adjuvant therapy choice in early breast cancer: better methods required for improved utility. J Clin Oncol, 27, 3715-6.
  13. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007). Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer registry. Cancer, 9, 1721-8.
  14. Cheang MC, Chia SK, Voduc D, et al (2009). Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst, 10, 736-50.
  15. Chu KC, Anderson WF, Fritz A, Ries LA, Brawley OW (2001). Frequency distributions of breast cancer characteristics classified by estrogen receptor and progesterone receptor status for eight racial/ethnic groups. Cancer, 1, 37-45.
  16. Chuthapisith S, Permsapaya W, Warnnissorn M, et al (2012). Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women. Asian Pac J Cancer Prev, 2, 459-62.
  17. Cobleigh MA, Vogel CL, Tripathy D, et al (1999). Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol, 9, 2639-48.
  18. Dawood S, Hu R, Homes MD, et al (2011). Defining breast cancer prognosis based on molecular phenotypes: results from a large cohort study. Breast Cancer Res Treat, 1, 185-92.
  19. Di Cosimo S, Baselga J (2010). Management of breast cancer with targeted agents: importance of heterogeneity. Nat Rev Clin Oncol, 3, 139-47.
  20. Ge QD, Lv N, Kong YN, et al (2012). Clinical characteristics and survival analysis of breast cancer molecular subtypes with hepatic metastases. Asian Pac J Cancer Prev, 13, 5081-6.
  21. Duffy SW, Tabar L, Vitak B, Warwick J (2006). Tumor size and breast cancer detection: what might be the effect of a less sensitive screening tool than mammography? Breast J, 1, 91-5.
  22. El Saghir NS, Assi HA, Jaber SM, et al (2014). Outcome of breast cancer patients treated outside of clinical trials. J Cancer, 5, 491-8.
  23. Gapstur SM, Dupuis J, Gann P, Collila S, Winchester DP (1996). Hormone receptor status of breast tumors in black, Hispanic, and non-Hispanic white women. An analysis of 13,239 cases. Cancer, 8, 1465-71.
  24. Hammond ME, Hayes DF, Dowsett M, et al (2010). American society of clinical oncology/college of American pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol, 16, 2784-95.
  25. Horita K, Yamaguchi A, Hirose K, et al (2001). Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer. Eur J Histochem, 1, 73-84.
  26. Huang HJ, Neven P, Drijkoningen M, et al (2005). Association between tumour characteristics and HER-2/neu by immunohistochemistry in 1362 women with primary operable breast cancer. J Clin Pathol, 58, 611-6.
  27. Ikpatt OF, Ndoma-Egba R (2003). Oestrogen and progesterone receptors in Nigerian breast cancer: relationship to tumour histopathology and survival of patients. Cent Afr J Med, 11, 122-6.
  28. Izadi P, Mehrdad N, Foruzandeh F, Reza NM (2012). Association of poor prognosis subtypes of breast cancer with estrogen receptor alpha methylation in Iranian women. Asian Pac J Cancer Prev, 13, 4113-7.
  29. Kallel I, Khabir A, Boujelbene N, et al (2012). EGFR overexpression relates to triple negative profile and poor prognosis in breast cancer patients in Tunisia. J Recept Signal Transduct Res, 3, 142-9.
  30. Jatoi I, Chen BE, Anderson WF, Rosenberg PS (2007). Breast cancer mortality trends in the United States according to estrogen receptor status and age at diagnosis. J Clin Oncol, 13, 1683-90.
  31. Joslyn SA (2002). Hormone receptors in breast cancer: racial differences in distribution and survival. Breast Cancer Res Treat, 1, 45-59.
  32. Kadivar M, Mafi N, Joulaee A, Shamshiri A, Hosseini N (2012). Breast cancer molecular subtypes and associations with clinicopathological characteristics in Iranian women, 2002-2011. Asian Pac J Cancer Prev, 13, 1881-6.
  33. Kaptain S, Tan LK, Chen B (2001). Her-2/neu and breast cancer. Diagn Mol Pathol, 3, 139-52.
  34. Khokher S, Qureshi MU, Mahmood S, Nagi AH (2013). Association of immunohistochemically defined molecular subtypes with clinical response to presurgical chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev, 14, 3223-8.
  35. Lazennec G, Bresson D, Lucas A, chauveau C, Vignon F (2001). ER beta inhibits proliferation and invasion of breast cancer cells. Endocrinology, 9, 4120-30.
  36. Lertsanguansinchai P, Chottetanaprasith T, Chatamra K, et al (2002). Estrogen and progesterone receptors status in Thai female breast cancer patients: an analysis of 399 cases at king chulalongkorn memorial hospital. J Med Assoc Thai, 1, 193-202.
  37. Li CI, Malone KE, Daling JR (2002). Differences in breast cancer hormone receptor status and histology by race and ethnicity among women 50 years of age and older. Cancer Epidemiol Biomarkers Prev, 7, 601-7.
  38. Payne SJ, Bowen RL, Jones JL, Wells CA (2008). Predictive markers in breast cancer-the present. Histopathology, 1, 82-90.
  39. Lund MJ, Butler EN, Hair BY, et al (2010). Age/race differences in HER2 testing and in incidence rates for breast cancer triple subtypes: a population-based study and first report. Cancer, 11, 2549-59.
  40. Najafi B, Anvari S, Roshan ZA (2013). Disease free survival among molecular subtypes of early stage breast cancer between 2001 and 2010 in Iran. Asian Pac J Cancer Prev, 10, 5811-6.
  41. Osborne CK, Yochmowitz MG, Knight WA 3rd, McGuire WL (1980). The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer, 12, 2884-8.
  42. Pegoraro RJ, Karnan V, Nirmul D, Joubert SM (1986). Estrogen and progesterone receptors in breast cancer among women of different racial groups. Cancer Res, 2, 2117-20.
  43. Prat A, Perou CM (2011). Deconstructing the molecular portraits of breast cancer. Mol Oncol, 1, 5-23.
  44. Rudat V, El-Sweilmeen H, Brune-Erber I, et al (2014). Identification of breast cancer patients with a high risk of developing brain metastases: a single-institutional retrospective analysis. BMC Cancer, 14, 289-95.
  45. Ruder AM, Lubin F, Wax Y, et al (1989). Estrogen and progesterone receptors in breast cancer patients. Epidemiologic characteristics and survival differences. Cancer, 1, 196-202.
  46. Runnak MA, Hazha MA, Hemin HA, et al (2012). A populationbased study of Kurdish breast cancer in northern Iraq: hormone receptor and HER2 status. A comparison with Arabic women and United States SEER data. BMC Womens Health, 12, 16-25.
  47. Sandhu DS, Sandhu S, Karwasra RK, Marwah S (2010). Profile of breast cancer patients at a tertiary care hospital in north India. Indian J Cancer, 47, 16-22.
  48. Stead LA, Lash TL, Sobieraj JE, et al (2009). Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res, 2, 18.
  49. Shak S (1999). Overview of the trastuzumab (Herceptin) anti-HER2 monoclonal antibody clinical program in HER2 overexpressing metastatic breast cancer. Herceptin Multinational Investigator Study Group. Semin Oncol, 12, 71-7.
  50. Slamon DJ, Clark GM, Wong SG, et al (1987). Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science, 4785, 177-82.
  51. Stanford JL, Szklo M, Brinton LA (1986). Estrogen receptors and breast cancer. Epidemiol Rev, 8, 42-59.
  52. Stierer M, Rosen H, Weber R, et al (1993). Immunohistochemical and biochemical measurement of estrogen and progesterone receptors in primary breast cancer. correlation of histopathology and prognostic factors. Ann Surg, 1, 13-21.
  53. Sughayer MA, Al-Khawaja MM, Massarweh S, Al-Masri M (2006). Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan. Pathol Oncol Res, 2, 83-6.
  54. Tamimi RM, Colditz GA, Hazra A, et al (2012). Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res Treat, 1, 159-67.
  55. Tarawneh M, Nimri O, Arkoob K, Al-Zaghal M (2010). Cancer incidence in Jordan 2010. National Cancer Registry, Ministry of Health/Jordan.
  56. Taucher S, Rudas M, Mader RM, et al (2003). Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer, 98, 2547-53.
  57. Tavassoli FA, Devilee P (2003). Pathology and genetics of tumours of the breast and female genital organs. IARC Press. Lyon pp 1-432.
  58. Vaidyanathan K, Kumar P, Reddy CO, et al (2010). ErbB-2 expression and its association with other biological parameters of breast cancer among Indian women. Indian J Cancer, 47, 8-15.
  59. Wittliff JL (1984). Steroid-hormone receptors in breast cancer. Cancer, 3, 630-43.

Cited by

  1. Effect of Hormone Therapy on Long-term Outcomes of Patients with Human Epidermal Growth Factor Receptor 2-and Hormone Receptor-Positive Metastatic Breast Cancer: Real World Experience in China vol.16, pp.3, 2015,
  2. Efficacy of TCH/TEC neoadjuvant chemotherapy for the treatment of HER‑2‑overexpressing breast cancer pp.1792-1082, 2015,
  3. First report on molecular breast cancer subtypes and their clinico-pathological characteristics in Eastern Morocco: series of 2260 cases vol.17, pp.1, 2017,