The relationship between tumour budding, the tumour microenvironment and survival in patients with invasive ductal breast cancer

Background: Tumour budding has previously been reported to predict survival in several solid organ tumours, including breast; however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between tumour budding, the tumour microenvironment and survival was examined in patients with invasive ductal breast cancer. Methods: Patients presenting between 1995 and 1998 were studied (n = 474). Using routine pathological sections, tumour budding was measured at the invasive margin and its association with clinicopathological characteristics and cancer-specific survival (CSS) was examined. Results: Tumour budding was associated with several adverse pathological characteristics, including lymph node involvement, lymph vessel invasion (LVI), increased tumour stroma percentage (TSP) and weaker local inflammatory infiltrative. Tumour budding was associated with reduced CSS (hazard ratio (HR) 2.08, 95% confidence interval (CI) 1.14-3.09, P = 0.004), independent of nodal status, molecular subtypes, tumour necrosis, CD8+; CD138+, LVI, blood vessel invasion and TSP. Further, tumour budding was independently associated with reduced CSS in node-negative patients (HR 2.63, 95% CI 1.16-5.92, P = 0.020) and those who have low TSP (HR 1.98, 95% CI 1.09-3.57, P = 0.024) and high-grade local inflammatory infiltrative (HR 2.27, 95% CI 1.35-5.36, P = 0.014). Conclusions: Tumour budding was a significant predictor of survival in patients with invasive ductal breast cancer, independent of adverse pathological characteristics and components of tumour microenvironment. The present study further confirms the clinical utility of both tumour and host-based factors of tumour microenvironment.