FREQUENCY AND CORRELATION OF MOLECULAR SUBTYPES OF BREAST CANCER WITH CLINICOPATHOLOGICAL FEATURES

Authors

  • Mohammad Akbar
  • Kehkashan Akbar
  • Danish Naveed

Abstract

Background: Traditional clinicopathological classification of breast cancer has limitations as tumours with similar clinical and histological features behave differently regarding outcome and responsiveness to chemo/immunotherapy. The objectives of the study were to determine the frequency of different molecular subtypes of breast cancer based on immunohistochemical staining and to find the correlation of each subtype with clinicopathological features. Methods: Sixty patients with histologically diagnosed invasive ductal carcinoma were enrolled in this cross sectional study. Immunohistological staining of the tumour samples and based on receptor status tumours were classified in four subtypes, Luminal A, Luminal B, HER2/neu oncogene amplification subtype and Tripple negative subtype. Clinical features, stage of disease at presentation and histopathological grade of the tumours was also recoded in each subtype. Prevalence of each subtype was calculated and correlation with clinical and pathological features was determined. Results: Mean age of the patients was 47.55 years. Protective role of breast feeding was not confirmed in this study as 58 (96.67%) patients breast fed their children. Only two (3.33%) patients gave family history of breast cancer in the study. Thirty three (55%) patients had grade 2 tumours, 26 (43.33%) had grade 3 tumours while only one patient had grade 1 tumour. HER2/neu amplification subtype was the most common molecular subclass in the study, comprising 30% of all the patients. Ten patients (16.67%) in this study belonged to triple negative group. Triple negative disease was found in younger women with mean age of 40–60 years. Conclusion: Breast cancer particularly triple negative disease was found in younger age group and patients usually present in advanced stage of their disease.HER2/neu positive breast cancer was the most common subtype in this study.Keywords: Oestrogen receptors, Progesterone receptors, Molicular Targeted therapy, Gene expression profiling, microarray analysis, Fluorescence, in situ hybridization

References

Perou CM, Sørlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406:747–52

Pusztai L, Mazounia C, Anderson K, Wu Y, Symmans WF. Molecular Classification of Breast Cancer: Limitations and Potential. The Oncologist 2006;11(8):868–77

Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 2001;98:10869–74.

Spitale A, Mazzola P, Soldini D, Mazzucchelli L, Bordoni A. Breast cancer classification according to immunohistochemical markers: clinicopathologic features and short-term survival analysis in a population-based study from the South of Switzerland. Ann Oncol 2009;20(4):628–35.

Hu Z, Fan C, Oh DS, Marron JS, He X, Qaqish BF, et al. The molecular portraits of breast tumours are conserved across microarray platforms. BMC Genomics 2006;7:96.

Gjuliano AE. Breast disorders. In: Doherty GM, editor. Current diagnosis and treatment Surgery. LANGE McGraw-Hill 2010 13th edition. page 279–304.

Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, et al. (editors). SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda, MD. Available at: http://seer.cancer.gov/csr/1975_2007/. Accessed in November 2009.

Anderson WF, Rosenberg PS, Menashe I, Mitani A, Pfeiffer RM. Age-Related Crossover in Breast Cancer Incidence Rates Between Black and White Ethnic Groups. J Natl Cancer Inst 2008;100(24):1804–14.

Rashid M U, Zaidi A, Torres D, Sultan F, Benner A, Naqvi B, et al. Prevalence of BRCA1 and BRCA2 mutations in Pakistani breast and ovarian cancer patients. Int J Cancer 2006;119:2832–9.

Naeem M, Khan N, Aman Z, Nasir A, Samad A, Khattak A. pattern of breast cancer: experience at lady reading hospital, Peshawar. J Ayub Med Coll Abbottabad 2008;20(4):22–5.

Press M F, Slamon D J, Flom K J, Park J, Zhou J Y, Bernstein L. Evaluation of HER-2/neu Gene Amplification and Overexpression: Comparison of Frequently Used Assay Methods in a Molecularly Characterized Cohort of Breast Cancer Specimens. J Clin Oncol 2002;20(14):3095–105.

Telli ML, Chang ET, Kurian AW, Keegan TH, McClure LA, Lichtensztajn D, et al. Asian race and breast cancer subtypes: A study from the California Cancer Registry. Breast Cancer Res Treat 2011;127:471–8

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, et al. Race breast cancer subtypes, and survival inthe Carolina Breast Cancer Study. JAMA 2006; 295(21):2492–502.

Kumar V, Tewari M, Singh U, Shukla HS. Significance of Her-2/neu protein over expression in Indian breast cancer patients. Indian J Surg 2007;69(4):122–8

Chang JC, Hilsenbeck SG, Fuqua SA. The promise of microarrays in the management and treatment of breast cancer. Breast Cancer Res 2005;7(3):100–4

Kakarala M, Rozek L, Cote M, Liyanage S, and Brenner DE. Breast cancer histology and receptor status characterization in Asian Indian and Pakistani women in the U.S. - a SEER analysis. BMC Cancer 2010;10:191.

Trivers KF, Lund MJ, Porter PL, Liff JM, Flagg EW, Coates RJ, et al. The epidemiology of triple-negative breast cancer, including race. Cancer Causes Control 2009;20(7):1071–82.

Lund MJ, Trivers KF, Porter PL, Coates RJ, Leyland-Jones B, Brawley OW, et al. Race and triple negative threats to breast cancer survival: a population-based study in Atlanta, GA. Breast Cancer Res Treat. 2009;113(2):357–70.

Peppercorn J. Breast Cancer in Young Women: A New Color or a Different Shade of Pink? J Clin Oncol 2008;26(20):3303–5.

Anders CK, Hsu DS, Broadwater G, Acharya CR, Foekens JA, Zhang Y, et al. Young Age at Diagnosis Correlates With Worse Prognosis and Defines a Subset of Breast Cancers With Shared Patterns of Gene Expression. J Clin Oncol 2008;26(20):3324–30.

Desai SB, Moonim MT, Gill AK, Punia RS, Naresh KN, Chinoy RF. Hormone receptor status of breast cancer in India: a study of 798 tumours. Breast 2000;9:267–70.

Ahmad S, Mahmood H, Kanwal S, Mahmood A, Ahmad K., Masood M., Faheem, M, Akbar N, Hafeez M. Relationship of Age at First Live Birth, Parity and Duration of Breast Feeding with Non Familial Breast Cancer in Pakistani Women. A Study of the Cancer Research Group Pakistan. Cancer Research 2009;69(24):1158

Most read articles by the same author(s)