Tumor Budding and Its Clinicopathological Correlations in Invasive Breast Carcinoma: A Cross-sectional Study

Introduction: Breast carcinoma is the leading cause of cancer-related mortality among women in India. Tumor budding is usually defined as isolated single cancer cells or clusters of up to four cancer cells located at the invasive tumor front. Tumor budding is associated with poor clinicopathological characteristics, such as Tumor size, tumor differentiation, lymph node invasion, lymphatic or vascular invasion, etc. One of the poor prognostic factors in breast carcinoma is an association between tumor budding and positive lymph node metastasis. Henceforth, tumor budding could be a reliable parameter that predicts the aggressive behaviour of tumor, overall survival, risk of recurrence, hormonal therapy response, distant metastasis along with the response to chemotherapy and targeted therapy. Tumor buds which are predominantly located at the invasive tumor front are associated with epithelial-mesenchymal transition (EMT) and are an essential part of the tumor microenvironment.

Aims: The aim of the study is to study tumor budding, predominantly located at the invasive tumor front representing EMT and its association with known clinicopathological parameters like age, tumor size, grade, laterality, LVI, lymph node metastases, treatment status and hormone receptor status in invasive breast carcinoma.

Materials and Methods: The index study is a cross sectional study of 50 mastectomy and lumpectomy specimens. It was conducted after approval from the ethics committee. Before conducting the study, informed consent was taken from all the participants whose biopsies were considered for the study. The duration of the study was 1.5 years from January 2022 to June 2023. The number of tumor buds was counted in 10 low-power fields (10x) of hematoxylin and eosin-stained sections. Tumor buds were further classified into low grade(<10/10 HPF) and high grade (
10/10 HPF) in most infiltrative areas at higher magnification (400x). Chi-square tests were used to know the association between tumor budding and the included variables of the study, pvalue<0.05 was considered statistically significant.

Results: A total of fifty cases of invasive breast carcinomas were included in this study. Here, 70%(35 cases) were >50 years of age, and 65% (33 cases) were in T2 (tumor size) category. Also, 82%(41 cases) of Invasive duct carcinoma, No specific type, 12% (6 cases) of mixed carcinomas followed by three cases, one is invasive lobular carcinoma (6%), others are invasive papillary carcinoma (6%) and mucinous carcinoma (6%). Moreover, 76% (38 cases) showed presence of lymphovascular invasion, 74% (37 cases) showed absence of necrosis, 54%(27 cases) were categorized as grade 2. High-grade tumor budding was seen in 54% (27 cases).
Conclusion: The following variables had a significant association with the tumor budding in the present study - Tumor size, TNM staging, treatment status, and lymphovascular invasion showing a p-value of <0.05. ER-positive tumors are also associated with high-grade tumor budding.