Tumor Budding, Desmoplasia, and Lymphocytic Infiltration as Predictors of Aggressiveness in Invasive Breast Carcinoma of No Special Type

Abstract Background: Invasive breast carcinoma of no special type (IBC-NST) constitutes the predominant subtype of breast cancer. While conventional histopathological parameters guide prognostic assessment, increasing evidence underscores the relevance of tumor microenvironment (TME) components – including tumor-infiltrating lymphocytes (TILs), desmoplasia, and tumor budding – in predicting tumor aggressiveness and clinical outcomes. Objectives: To systematically evaluate the TME features (TILs, desmoplasia, and tumor budding) in IBC-NST and determine their associations with established histopathological parameters (tumor grade, lymph node status, and lymphovascular invasion [LVI]). The influence of patient age was also assessed. Materials and Methods: A retrospective cross-sectional study was conducted on 96 IBC-NST cases from January 2023 to January 2025. Formalin-fixed, paraffin-embedded tissue sections were evaluated for TILs (per International TILs Working Group 2014), desmoplasia (graded 0–3), and tumor budding (categorized as low or high). Associations with histopathological features were analyzed using Chi-square/Fisher’s exact tests, and multivariate logistic regression identified independent predictors of high tumor grade. Results: High TILs were significantly associated with high-grade tumors ( P = 0.041), lower LVI ( P = 0.003), and negative lymph node status ( P = 0.047). Severe desmoplasia and tumor budding were significantly linked with high-grade tumors ( P = 0.001 and P = 0.005, respectively), LVI, and nodal metastasis. In multivariate analysis, LVI (odds ratio [OR] = 4.65), tumor budding (OR = 3.42), and severe desmoplasia (OR = 2.91) emerged as independent predictors of high tumor grade. High TILs did not retain independent significance ( P = 0.211). Conclusions: Morphological features of TME – particularly tumor budding, desmoplasia, and LVI – are reliable independent predictors of tumor grade in IBC-NST, surpassing immune infiltration alone. Integrating these parameters into routine pathology reporting may enhance prognostication and guide personalized treatment planning.