Tumor budding in invasive breast carcinoma: an emerging prognostic factor


  • Reetika Devashwar Department of Lab Sciences and Molecular Medicine, Army Hospital Research and Referral, Delhi, India
  • P. S. Mishra Department of Lab Sciences and Molecular Medicine, Army Hospital Research and Referral, Delhi, India
  • S. Venkatesan Armed Forces Transfusion Centre, Delhi, India
  • Jasvinder Kaur Bhatia Department of Lab Sciences and Molecular Medicine, Army Hospital Research and Referral, Delhi, India




Breast carcinoma, Tumor budding, Lymphovascular invasion, Hormonal status


Background: Tumor budding refers to single or small cluster of tumor cells detached from the main tumor mass in histological sections. In colon cancer high tumor budding is associated with worse prognosis and correlates with metastatic lymph nodes. We studied tumor budding in modified radical mastectomy specimens to evaluate its utility as a prognostic factor by correlating high tumor budding score with known prognostic markers of breast cancer like axillary lymph nodal metastasis, clinical staging, tumor size, lymphovascular invasion, hormonal status and pathological grading. Aim was to evaluate tumor budding in invasive breast carcinoma and to describe clinical features and histopathological spectrum of Invasive Breast Carcinoma with/without lymph node metastasis on H&E slides. Secondly, to find association between grades of tumor budding and various clinical, gross, microscopic and immunohistochemical variables.

Methods: The present study is a cross sectional study of 70 modified radical mastectomy specimens from June 2018 to Dec 2022. Along with tumor budding various prognostic parameters like hormonal markers, pathological grading and clinical grading were evaluated. Immunohistochemical marker Pancytokeratin was utilized for counting the tumor buds, wherever necessary. Statistical Analysis: Chi Square test was utilized to study significant differences between variables, p<0.05 was considered statistically significant.

Results: A high tumor budding score (≥4/HPF) had significant association with axillary lymph node involvement and clinical staging.

Conclusions: In our study we detected the association of high tumor budding, PTB in invasive breast carcinoma with axillary lymph node involvement and clinical staging. Hence our results highlight the importance of tumor budding as a prognostic factor and submit that this histological feature could be included in diagnostic protocols just as in carcinoma of the colon.


Lap P, Tan KL, Chen B Correlation of HER-2status with Estrogen and progesterone receptors and Histologic features in 3,655 Invasive Breast Carcinoma. Am J Clin Pathol. 2005;123(4):541-6.

Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol. 2017;13(4):289-95.

Brunicardi CF. Schwartz’s Principle of Surgery. 11th ed. USA: Mc-Graw Hill; 2015: 453-500.

Park S. Textbook of Preventive and Social Medicine. 25th ed. India: Banarsidas Bhanot Publishers; 2021: 378-380.

Kumar V, Abbas AK, Aster JC. Pathological Basis of Disease. 9th ed. Philadelphia: Elsevier; 2015: 1051-1063.

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. 2001;98:10869-74.

Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, et al. Molecular portraits of human breast tumours. Nature. 2000;406(6797):747-52.

Polyak K, Hu M. Do myoepithelial cells hold the key for breast tumor progression? J Mammary Gland Biol Neoplas. 2005;10(3):231-47.

van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW et al. A geneexpression signature as a predictor of survival in breast cancer. N Engl J Med. 2001;347:1999-2009.

Gokmen-Polar Y, Badve S. Breast cancer prognostic markers: where are we now? MLO Med Lab Obs. 2012;44(22):24-5.

Wessels LF, van Welsem T, Hart AA, van’t Veer LJ, Reinders MJ, Nederlof PM. Molecular classification of breast carcinomas by comparative genomic hybridization: 80 a specific somatic genetic profile for BRCA1 tumors. Cancer Res. 2002;62:7110-7.

Almangush A, Bello IO, Keski-Säntti H. Depth of invasion, tumor budding, and worst pattern of invasion: prognostic indicators in early-stage oral tongue cancer. Head Neck. 2014;36(6):811-8.

Sriwidyani N, Manuaba I, Alit-Artha I, Mantik-Astawa I. Tumor budding in carcinoma: relation to E-Cadherin, MMP-9 expression, and metastasis risk. Bali Med J. 2016;5(3):497-501.

Lugli A, Karamitopoulou E, Zlobec I. Tumour budding: a promising parameter in colorectal cancer. Br J Cancer. 2012;106:1713-7.

Lugli A. Recommendations for reporting tumor budding in colorectal cancer based. Modern Pathol. 2017;30(9):1299-311.

Guzinska-Ustymowicz K. The role of tumour budding at the front of invasion and recurrence of rectal carcinoma. Anticancer Res. 2005;25(2B):1269-72.

Karamitopoulou E, Zlobec I, Born D, Kondi-PafitiA, Lykoudis P, Mellou A, et al. Tumour budding is a strong and independent prognostic factor in pancreatic cancer. Eur J Cancer. 2013;49(5):1032-9.

Ellis O, Collins L, Ichihara S, Mac Grogan G. Invasive carcinoma of no special type In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, van de Vijver MJ, eds. WHO classification of tumours of the breast. 4th ed. France: IARC press; 2012: 34.

Colditz G, Chia KS. Invasive breast carcinoma: Introduction and general features. In: Lakhani SR, Ellis IO, Schnitt SJ, Tan PH, eds. WHO Classification of Tumors of the Breast. 4th ed. France: IARC press; 2012: 14.

Polyak K, Hu M. Do myoepithelial cells hold the key for breast tumor progression? J Mammary Gland Biol Neoplas. 2005;10(3):231-47.

Renuka IV, Madhavi K, Premalatha P. Tumor budding in invasive carcinoma of breast of no special type (NST): value as a prognostic factor. J Diagnos Pathol Oncol. 2019;4(2):125-9.

Gabal SM, Bassam AM, Sedqi ME. Tumour budding and MMP-2 expression in breast invasive ductal carcinoma. J Clin Diagnos Res. 2018;12(5):EC25.

Salhia B, Trippel M, Pfaltz K. High tumor budding stratifies breast cancer with metastatic properties. Breast Cancer Res Treat. 2015;150(2):363-71.

Fulga V, Rudico L, Balica AR, Cimpean AM, Saptefrati L, Raica M. Invasive ductal carcinoma of no special type and its corresponding lymph node metastasis: do they have the same immunophenotypic profile? Pol J Pathol. 2015;66(1):30-7.

Li X, Wei B, Sonmez C, Li Z, Peng L. High tumor budding count is associated with adverse clinicopathologic features and poor prognosis in breast carcinoma. Hum Pathol. 2017;66:222-9.

Falck AK, Fernö M, Bendahl PO, Rydén L. St Gallen molecular subtypes in primary breast cancer and matched lymph node metastases-aspects on distribution and prognosis for patients with luminal A tumours: results from a prospective randomised trial. BMC Cancer. 2013;13:558-83.

Masilamani DS. Evaluation of clinicopathologic significance of tumor budding in breast carcinoma. Int J Clin Diagn Pathol. 2019;2(1):171-3.

Liang F, Cao W, Wang Y. The prognostic value of tumor budding in invasive breast cancer. Pathol Res Pract. 2013;209(5):269-75.

Gujam FJ, McMillan DC, Mohammed ZM. The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer. Br J Cancer. 2015;113(7):1066-74.

Agarwal R, Khurana N, Singh T. Tumor budding in infiltrating breast carcinoma: correlation with known clinicopathological parameters and hormone receptor status. Indian J Pathol Microbiol. 2019;62(2): 222-5

Lugli A, Kirsch R, Ajioka Y Recommendations for reporting tumor budding in colorectal cancer based on the international tumor budding consensus conference (ITBCC) 2016. Mod Pathol. 2017;30(9):1299-311.

Lloyd A, Ryan E, Boland M. The histopathological and molecular features of breast carcinoma with tumour budding a systematic review and meta-analysis. Breast Cancer Res Treat. 2020;183(3):503-14.

Aleskandarany MA, Green AR, Benhasouna AA, Barros FF, Neal K, Reis-Filho JS, et al. Prognostic value of proliferation assay in the luminal, Her2-positive, and triple-negative biologic classes of breast cancer. Breast Cancer Res. 2012;14:21-8.

Rummel S, Hueman MT, Costantino N, Shriver CD, Ellsworth RE. Tumour location within the breast: Does tumour site have prognostic ability? Ecancer Med Sci. 2015;9:552.

Huang T, Bao H, Meng YH, Zhu JL, Chu XD, Chu XL, Pan JH. Tumour budding is a novel marker in breast cancer: the clinical application and future prospects. Ann Med. 2022;54(1):1303-12.

Voutsadakis IA. Prognostic role of tumor budding in breast cancer. World J Exp Med. 2018;8(2):12-7.




How to Cite

Devashwar, R., Mishra, P. S., Venkatesan, S., & Bhatia, J. K. (2024). Tumor budding in invasive breast carcinoma: an emerging prognostic factor. International Journal of Research in Medical Sciences, 12(6), 1931–1935. https://doi.org/10.18203/2320-6012.ijrms20241536



Original Research Articles