Title: Molecular Classification of Breast Carcinoma by Immuno-histochemical Analysis: A Tertiary Cancer Hospital Outcome in Bangladesh

Authors: Dr Md. Rassell, Dr K. M. Shaiful Islam, Dr Anindita Paul, Dr Shaila Parveen, Dr Zillur Rahman Bhuiyan

 DOI: https://dx.doi.org/10.18535/jmscr/v8i7.52

Abstract

Background: Carcinoma of the breast is a heterogeneous disease & the most common malignancy in women. The type of carcinoma determined by the involvement of specific cells in the breast that are affected. In Situ breast cancer starts in ductal & lobular epithelium having no penetration beyond the basement membrane. Invasive or infiltrating breast cancer goes beyond the basement membrane & infiltrate surrounding breast tissue.

Objective: The objective of this study was to identify the subtype of breast carcinoma by immune-histochemical analysis.

Materials & Method: This cross-sectional study was conducted in the department of surgical oncology, in a tertiary cancer hospital, Dhaka, Bangladesh from March 2015 to April 2016. 121 admitted patients were finalized for the study. Immuno-histochemical staining was performed to classify the subtypes of breast carcinoma.

Results: The mean age of the patients was 42.85(±9.6). Out of 121 patients, 98.34% were breast lump, 27.27% nipple discharge and 52% were upper outer quadrant lump. Among the total patients, Luminal A type was highest 38(31.4%), TNBC 37(30.54%), HER2 was 26(21.48%), Luminal B type was 16(13.22%) and 4(3.3%) as others. According to the molecular classification, well-differentiated tumors, Luminal A, Luminal B, TNBC, HER2, and other observed in 7, 3, 11, 4 and 0 cases and in moderately differentiated tumors Luminal A, Luminal B, TNBC, Her2, and others were observed in 28, 9, 6, 3, and 0 cases. In poorly differentiated tumors Luminal A, Luminal B, TNBC, Her2, and others observed in 3, 4, 20, 19, and 4 cases.

Conclusion: The most common tumor subtype is the Luminal A tumors, followed by triple-negative tumors. Luminal A and triple-negative tumors were found to be linked with increased frequency of lobular carcinomas. The HER2-positive and triple-negative tumors were associated with an increased frequency of large tumor size and poorly differentiated carcinomas as well as a more aggressive manifestation of cancer.

Keywords: Molecular sub-type, Immuno-histochemistry (IHC), breastcarcinoma (BC).

References

  1. Kumar V, Abbas AK, Aster JC. Robbins and Cotran Pathologic Basis of Disease, 9th edition, Elsevier. 2015; 1051-1052.
  2. Perou CM, Sorlie T, Eisen MB et al. Molecular portraits of human breast tumors. Nature. 2000; 406(6797):747–752.
  3. Prat A, Cheang MCU, Martín M et al. Prognostic significance of progesterone receptor–positive tumor cells within immunohistochemically defined luminal a breast cancer. J ClinOncol. 2013; 31(2):203–209..
  4. Cancer Registry Report 2008-2010. Published by Department of Cancer Epidemiology, National Institute of Cancer Research and Hospital, Published in December 2013, p-11.
  5. Stewart BW, Kleihues P (2003), editors. World Cancer report. Lyon: IARC Press.
  6. Parkin DM, Bray F, Ferlay J, Pisani P (2005). Global cancer statistics, 2002. CA: a cancer journal for clinicians; 55:74-108.
  7. Brown M, Goldie S, Draisma G, Harford J (2006). Health service interventions for cancer control in developing countries in Disease Control Priorities in Developing Countries. Oxford University Press,vol. 2, pp. 569-90.
  8. World Cancer Research Fund. Available from: http://www.wcrf.org/ cancer_facts/women-breast-cancer.php/. Accessed March 10, 2016.
  9. Glass AG, Lacey JV Jr, Carreon JD, Hoover RN (2007). Breast cancer incidence, 1980-2006: combined roles of menopausal hormone therapy, screening mammography, and estrogen receptor status. J Natl Cancer Inst; 99:1152-1161.
  10. Viale G: The current state of breast cancer classification. Ann Oncol 2012, 23 (Suppl 10): x207–x210.
  11. Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, et al. (2003) Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl AcadSci U S A 100: 8418–8423.
  12. Sorlie T, Perou CM, Tibshirani R, et al (2001). Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl AcadSci USA.; 98:10869-10874.
  13. Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, Livasy C, Carey LA, Reynolds E, Dressler L, Nobel A, Parker J, Ewend MG, Sawyer LR, Wu J, Liu Y, Nanda R, Tretiakova M, Ruiz Orrico A, Dreher D, Palazzo JP, PerreardL, Nelson E, Mone M, Hansen H, Mullins M, Quackenbush JF, Ellis MJ, Olopade OI, Bernard PS, et al (2006). The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics, 7:96.
  14. Farmer P, Bonnefoi H, Becette V, Tubiana-Hulin M, Fumoleau P, Larsimont D, Macgrogan G, Bergh J, Cameron D, Goldstein D, Duss S, Nicoulaz A-L, Brisken C, Fiche M, Delorenzi M, Iggo R (2005). Identification of molecular apocrine breast tumours by microarray analysis. Oncogene, 24:4660–4671.
  15. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y, Pietenpol JA (2011). Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest, 121:2750–2767.
  16. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, Hu Z, Rasmussen KE, Jones LP, Assefnia S, Chandrasekharan S, Backlund MG, Yin Y, Khramtsov AI, Bastein R, Quackenbush J, Glazer RI, Brown PH, Green JE, Kopelovich L, Furth PA, Palazzo JP, Olopade OI, Bernard PS, Churchill GA, Van Dyke T, Perou CM (2007). Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol; 8:R76.
  17. Prat A, Parker JS, Karginova O, Fan C, Livasy C, Herschkowitz JI, et al (2010). Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res; 12:68.
  18. Peddi, Matthew J.Ellis, and Cynthia Ma (2012). Molecular Basis of Triple Negative Breast Cancer and Implications for Therapy. Hindawi Publishing Corporation. International Journal of Breast Cancer. Article ID 217185, 7 pages.
  19. Tavassoli FA, Devilee P (2003). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press.
  20. Hammond MEH, Hayes DF, Wolff AC, 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 Oncol Practice, 6, 15-7.
  21. Wolff AC., Hammond EH, Schwartz KL, et al (2007). American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med, 33, 19-33.
  22. Gnant M, Harbeck N, Thomssen C (2011). St Gallen 2011: Summary of the consensus Discussion. Breast Cancer, 6, 136-41.
  23. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006). Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA; 295:2492-2502.
  24. Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, Ollila DW, Sartor CI, Graham ML, Perou CM (2007). The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res; 13:2329-2334
  25. Rakha EA, Reis-Filho JS, Ellis IO (2008). Basal-like breast cancer: a critical review. J ClinOncol.; 26:2568-2581.
  26. 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.; 101:736-750.
  27. Desmedt C, Haibe-Kains B, Wirapati P, et al (2008). Biological processes associated with breast cancer clinical outcome depend on the molecular subtypes. Clin Cancer Res.; 14:5158-5165.
  28. Zhao X, Malhotra GK, Lele SM, Lele MS, West WW, Eudy JD, et al (2010). Telomerase-immortalized human mammary stem/progenitor cells with ability to self-renew and differentiate. Proc Natl AcadSci USA; 107:14146-51.
  29. Fan C, Oh DS, Wessels L, Weigelt B, Nuyten DS, Nobel AB, van’t Veer LJ, Perou CM (2006). Concordance among gene-expression-based predictors for breast cancer. N Engl J Med; 355:560-569.
  30. Hayes DF, Thor AD, Dressler LG, Weaver D, Edgerton S, Cowan D, Broadwater G, Goldstein LJ, Martino S, Ingle JN, Henderson IC, Norton L, Winer EP, Hudis CA, Ellis MJ, Berry DA (2007). Cancer and Leukemia Group B (CALGB) Investigators. HER2 and response to paclitaxel in node-positive breast cancer. N Engl J Med; 357:1496-1506.
  31. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS (2005). ATAC Trialists’ Group. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet; 365:60-62.
  32. Brouckaert O, Pintens S, Van Belle V, Van Huffel S, Camerlynck E, Amant F, Leunen K, Smeets A, Berteloot P, Van Limbergen E, Decock J, Hendrickx W, Weltens C, Van den Bogaert W, VandenBempt I, Drijkoningen M, Paridaens R, Wildiers H, Vergote I, Christiaens MR, Neven P (2009). Short-term outcome of primary operated early breast cancer by hormone and HER-2 receptors. Breast Cancer Res Treat; 115:349-358.

Corresponding Author

Dr Md. Rassell

Assistant Professor, Department of Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh