DOI QR코드

DOI QR Code

HER-2/neu Status: A Neglected Marker of Prognostication and Management of Breast Cancer Patients in India

  • Zubeda, Syeda (Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre) ;
  • Kaipa, Prabhakar Rao (Department of Genetics, Osmania University) ;
  • Shaik, Noor Ahmad (Princess Al-Jawhara Centre of Excellence in Research of Hereditary Disorders, Department of Genetic Medicine, Faculty of Medicine, King Abdul Aziz University) ;
  • Mohiuddin, Mohammed Khaliq (Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre) ;
  • Vaidya, Sireesha (Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre) ;
  • Pavani, Boddana (Department of Genetics and Molecular Medicine, Kamineni Hospitals) ;
  • Srinivasulu, Mukta (Department of Surgical Oncology, Mehdi Nawaz Jung Hospital) ;
  • Latha, Manolla Madhavi (Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre) ;
  • Hasan, Qurratulain (Department of Genetics and Molecular Medicine, Vasavi Medical and Research Centre)
  • Published : 2013.04.30

Abstract

Background: Categorizing breast tumors based on the ER, PR and HER/Neu 2 receptor status is necessary in order to predict outcome and assist in management of breast cancer. Herfe we assessed this question in South Indian patients. Materials and Methods: A total of 619 formalin fixed paraffin embedded breast tumor tissues were collected from pathology archives after receipt of ethical clearance. With the help of primary and secondary conjugated antibodies, expression status of ER, PR and HER2/neu was determined. All the experimental data were assessed for correlations with histopathological features of tumors and clinical presentation of the subjects. Results: In the present study, the ages ranged from 20-87 years with a mean of $50.0{\pm}12.q$ years, and majority of the tumors (84%) were of infiltrating duct cell carcinoma type. Assessment of ER, PR and Her-2/neu expression showed that 46% were triple negative. Interestingly, an inverse relation between ER, PR and HER-2/neu was apparent in 41.2% (p<0.0001) of the tumors, of which 24.5% (p<0.0001) were ER and PR co-negative but HER-2 positive. Conclusions: ER and PR positive tumors are less common (i.e<30%) compared to HER-2/neu positive tumors (i.e>50%) in Indian breast cancer patients, underlining the need for effective diagnostic screening and specific therapeutic managements in order to improve the survival rate of patients in low resource countries such as India.

References

  1. Al-Ahwal MS (2006). HER-2 positivity and correlations with other histopathologic features in breast cancer patients hospital based study. J Pak Med Assoc, 56, 65-8.
  2. Almasri NM, Al Hamad M, (2005). Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan. Breast Cancer Res, 7, 598-604. https://doi.org/10.1186/bcr1200
  3. Ambroise M, Ghosh M, Mallikarjuna VS, Kurtian A (2011). Immuno histochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev, 12, 625-9.
  4. Ariga R, Zarif A, Korasick J, et al (2005). Correlation of her-2/ neu gene amplification with other prognostic and predictive factors in female breast carcinoma. Breast, 11, 278-80. https://doi.org/10.1111/j.1075-122x.2005.21463.x
  5. Barnes DM, Harris WH, Smith P, Millis RR, Rubens RD (1996). Immunohistochemical determination of oestrogen receptor: comparison of different methods of assessment of staining and correlation with clinical outcome of breast cancer patients. Br J Cancer, 74, 1445-51. https://doi.org/10.1038/bjc.1996.563
  6. Desai SB, Moonim MT, Gill AK, et al (2000). Hormone receptor status of breast cancer in India: a study of 798 tumours. Breast, 9, 267-70. https://doi.org/10.1054/brst.2000.0134
  7. Dutta SM CV, Chopra SM BGS, Sahai Lt CK, Nema B SK, (2008). Hormone receptors, Her-2/Neu and chromosomal aberrations in breast cancer. MJAFI, 64, 11-5.
  8. Ferlay J, Shin HR, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  9. Francis GD, Dimech M, Giles L, Hopkins A (2007). Frequency and reliability of oestrogen receptor, progesterone receptor and HER2 in breast carcinoma determined by immunohistochemistry in Australasia: results of the RCPA quality assurance program. J Clin Pathol, 60, 1277-83. https://doi.org/10.1136/jcp.2006.044701
  10. Higgins MJ, Baselga J (2011). Targeted therapies for breast cancer. J Clin Invest, 121, 3797-803. https://doi.org/10.1172/JCI57152
  11. 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. https://doi.org/10.1136/jcp.2004.022772
  12. Ivkovic-Kapicl T, Knezevic-Usaj S, Djilas-Ivanovic D, Panjkovic M (2007). Correlation of HER-2/neu protein overexpression with other prognostic and predictive factors ininvasive ductal breast cancer. In Vivo, 21, 673-8.
  13. Kamil M, Yusuf N, Khalid I, et al (2010). Association between HER-2/neu over-expression and clinico-pathologic parametersof breast cancer in northern Malaysia. Ceylon Med J, 55, 9-13.
  14. Kraft P, Haiman CA (2010). GWAS identifies a common breast cancer risk allele among BRCA1 carriers. Nat Genet, 42, 819-20. https://doi.org/10.1038/ng1010-819
  15. Kumar V, Abbas AK, Fausto N, Aster J (2010). Robbins and cotran pathologic basis of disease, 8th edn. 1119-54, USA, Elsevier.
  16. Kumar V, Tewari M, singh U, Shukla HS (2007). Significance of Her-2/neu protein over expression in Indian breast cancer patients. Indian J Surg, 69, 122-8. https://doi.org/10.1007/s12262-007-0002-8
  17. Lal P, Tan LK, Chen B (2005). Correlation of HER-2 status with estrogen and progesterone receptors and histologic features in 3,655 invasive breast carcinomas. Am J Clin Pathol, 123, 541-6. https://doi.org/10.1309/YMJ3A83TB39MRUT9
  18. Liu Y, el-Ashry D, Chen D, Ding IY, Kern FG (1995). MCF-7 breast cancer cells over expressing transfected c-erbB-2 have an in vitro growth advantage in estrogen-depleted conditions and reduced estrogen-dependence and tamoxifin-sensitivity in vivo. Breast Cancer Res Treat, 34, 97-117. https://doi.org/10.1007/BF00665783
  19. Livi L, Meattini I, Saieva C, et al (2011). Prognostic value of positive human epidermal growth factor receptor 2 status and negative hormone status in patients with T1a/T1b, lymph node-negative breast cancer. Cancer, 118, 3236-43.
  20. Lovekin C, Ellis IO, Locker A, et al (1991). c-erbB-2 oncoprotein expression in primary and advanced breast cancer. Br J Cancer, 63, 439-43. https://doi.org/10.1038/bjc.1991.101
  21. Lu M, Whelan SA, He J, et al (2010). Hydrophobic proteome analysis of triple negative and hormone receptor Her2 negative breast cancer by mass spectrometer. Clin Proteomics, 3, 93-103
  22. Marsiglinate S, Muscella A, Ciardo V, et al (1993). Enzymelinked immunosorbent assay of HER-/neu gene product (p185) in breast cancer: its correlation with sex steroid receptors, cathepsins D and histologic grades. Cancer Lett, 75, 195-206. https://doi.org/10.1016/0304-3835(93)90062-E
  23. Masood S (2010). The current status of breast cancer among resource-limited countries. Middle East J Cancer, 1, 1-4. https://doi.org/10.1080/21520841003741463
  24. Massarweh S, Schiff R (2007). Unraveling the mechanisms of endocrine resistance in breast cancer: new therapeutic opportunities. Clin Cancer Res, 13, 1950-4. https://doi.org/10.1158/1078-0432.CCR-06-2540
  25. Misrahi M, Atger M, dAuriol L, et al (1987). Complete amino acid sequence of the human progesterone receptor deduced from cloned cDNA. Biochem Biophys Res Commun, 143, 740-8. https://doi.org/10.1016/0006-291X(87)91416-1
  26. Munjal K, Ambaye A, Evans MF, et al (2009). Immunohistochemical analysis of ER, PR, Her2 and CK5/6 in infiltrative breast carcinomas in Indian patients. Asian Pac J Cancer Prev, 10, 773-89.
  27. Naeem M, Nasir A, Aman Z, Ahmad T, Samad A (2008). Frequency of HER-2/neu receptor positivity and its association with other features of breast cancer. J Ayub Med Coll Abbottabad, 20, 23-6.
  28. Oh AS, Lorant LA, Holloway JN, et al (2001). Hyperactivation of MAPK induces loss of ER alpha expression in breast cancer cells. Mol Endocrinol, 15, 1344-59. https://doi.org/10.1210/me.15.8.1344
  29. Patil VW, Singhai R, Patil A V, Gurav (2011). PD Triple-negative (ER, PgR, HER-2/neu) breast cancer in Indian women. Breast Cancer: Targets and Therapy, 3, 9-19.
  30. Ratnatunga N, Liyanapathirana LV (2007). Hormone receptor expression and Her/2neu amplification in breast carcinoma in a cohort of Sri Lankans. Ceylon Med J, 52, 133-6.
  31. Rhodes A, Jasani B, Balaton AJ, Barnes DM, Miller KD (2000). Frequency of oestrogen and progesterone receptor positive by immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value, and mammographic screening. J Clin Pathol, 53, 688-96. https://doi.org/10.1136/jcp.53.9.688
  32. Shyamala G, Yang X, Cardiff RD, Dale E (2000). Impact of progesterone receptor on cell-fate decisions during mammary gland development. Proc Natl Acad Sci USA, 97, 3044-9. https://doi.org/10.1073/pnas.97.7.3044
  33. Taucher S, Rudas M, Mader RM, et al (2003). Do we need HER-2/neu testing for all patients with primary breast carcinoma? Cancer, 198, 2547-53.
  34. 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. https://doi.org/10.4103/0019-509X.58852

Cited by

  1. Expression and Significance of ER, PR, VEGF, CA15-3, CA125 and CEA in Judging the Prognosis of Breast Cancer vol.14, pp.6, 2013, https://doi.org/10.7314/APJCP.2013.14.6.3937
  2. Clinico-Morphological Profile and Receptor Status in Breast Cancer Patients in a South Indian Institution vol.15, pp.18, 2014, https://doi.org/10.7314/APJCP.2014.15.18.7839
  3. Triple Negative Breast Cancer vol.15, pp.6, 2014, https://doi.org/10.7314/APJCP.2014.15.6.2427
  4. Investigation of Antitumor Effects of Sorafenib and Lapatinib Alone and in Combination on MCF-7 Breast Cancer Cells vol.15, pp.7, 2014, https://doi.org/10.7314/APJCP.2014.15.7.3185
  5. Expression and significance of DOK2 in colorectal cancer pp.1792-1082, 2014, https://doi.org/10.3892/ol.2014.2672
  6. HER-2 Positive Breast Cancer - a Mini-Review vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.1609
  7. Pedigree and BRCA gene analysis in breast cancer patients to identify hereditary breast and ovarian cancer syndrome to prevent morbidity and mortality of disease in Indian population vol.39, pp.2, 2017, https://doi.org/10.1177/1010428317694303
  8. MED12 somatic mutations encompassing exon 2 associated with benign breast fibroadenomas and not breast carcinoma in Indian women vol.120, pp.1, 2018, https://doi.org/10.1002/jcb.27293
  9. LncRNA AWPPH promotes the growth of triple-negative breast cancer by up-regulating frizzled homolog 7 (FZD7) vol.38, pp.6, 2018, https://doi.org/10.1042/BSR20181223
  10. Triple Negative Breast Cancer: Experience from a North Indian Tertiary Care Center vol.80, pp.5, 2018, https://doi.org/10.1007/s12262-017-1638-7
  11. Patterns of Care of Breast Cancer Patients in a Rural Cancer Center in Western India vol.9, pp.3, 2018, https://doi.org/10.1007/s13193-018-0748-4