Histological factors for accurately predicting first locoregional recurrence of invasive ductal carcinoma of the breast

Abstract

The accurate assessment of the risk of first locoregional recurrence is very important for improving the survival of patients with invasive ductal carcinoma of the breast. The present study investigated which histological factors (both well-known histological factors and factors that we have proposed) were the most capable of accurately predicting first locoregional recurrence among 1042 patients with invasive ductal carcinoma and various tumor statuses (overall, nodal status, Union Internationale Contre le Cancer pathological TNM stage, adjuvant therapy status, and adjuvant radiotherapy status) using multivariate analyses by the Cox proportional hazard regression model. The present study clearly demonstrated that the best factor for accurately predicting locoregional recurrence was grade 3 lymph vessel tumor embolus (>4 mitotic figures and >6 apoptotic figures in tumor embolus), followed by type 2 invasive ductal carcinoma (negative for fibrotic foci but positive for atypical tumor-stromal fibroblast), grade 2 lymph vessel tumor embolus (1-4 mitotic figures and >0 apoptotic figures in tumor embolus; >0 mitotic figures and 1-6 apoptotic figures in tumor embolus), primary invasive tumor cell-related factors (>19 mitotic figures, presence of tumor necrosis, presence of skin invasion) and >5 mitotic figures in metastatic carcinomas to the lymph node. Our proposed factors were superior to well-known histological factors of primary invasive tumors or clinicopathological factors for the accurate prediction of first locoregional recurrence in patients with invasive ductal carcinoma of the breast.

Figure 1

(a–c) Type 2 invasive ductal carcinoma. One atypical tumor‐stromal fibroblast with a large spindle nucleus is visible in the tumor stroma (arrow). The fibroblast was stained negative for AE1/3 (arrow, b) and positive for smooth muscle actin (arrow, c). The invasive tumor cells were stained positive for AE1/3 (b). (d–f) Grade 3 lymph vessel tumor emboli. Three large lymph vessel tumor emboli are present, and the wall of one of the tumor lymph vessels containing the embolus was positive for D2–40 (arrowheads, e). Five mitotic tumor cells (arrows) and eight apoptotic tumor cells (arrowheads) are visible within the tumor embolus (f).

Figure 2

First locoregional recurrence‐free survival curves for overall patients with invasive ductal carcinoma (a and b). (a) Patients with grade 3 lymph vessel tumor emboli had the shortest locoregional recurrence‐free survival curve. Patients with grade 2 lymph vessel tumor emboli also had a significantly shorter locoregional recurrence‐free survival curve than patients with grade 1 lymph vessel tumor emboli or patients with grade 0 lymph vessel tumor emboli. (b) Patients with type 2 invasive ductal carcinoma had a significantly shorter first locoregional recurrence‐free survival curve than patients with type 1 invasive ductal carcinoma, patients with type 3 invasive ductal carcinoma and patients with type 4 invasive ductal carcinoma.