Background/Objectives: The fundamental classification based on white, brown, pink, and beige adipose tissue morphology together with fat vacuole content released into the tumor microenvironment incompletely defines breast cancer-associated adipose tissue (BCAAT) heterogeneity and does not sufficiently explain its controversial impact on invasion, recurrence, or survival in breast cancer (BC). We aim to expand BCAAT characterization by systematically evaluating stromal cellular elements within peritumoral adipose tissue, including CD34-positive fibroblasts, smooth muscle actin (SMA)-positive myofibroblasts, inflammatory cells, and microvascular structures to define distinct BCAAT subgroups. Methods: CD34 and smooth muscle actin (SMA) double immunohistochemistry was performed on 109 BC tissue specimens from patients aged 35 to 79 years old, followed by microscopic evaluation of cellular and vascular components inside peritumor adipose tissue. Microscopic findings were then correlated to age, body mass index (BMI), lymphovascular (LVI) and perineural invasion (PnI), recurrence (R), and tertiary lymphoid structures (TLSs). Results: Four BCAAT subtypes have been identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed-vascular and inflammatory-rich (VI^Rich_BCAAT). The F^Rich_BCAAT subtype predominates for the age subgroup 35 to 49 years old and is a significantly worse prognostic factor for survival (p = 0.022). For the age subgroup of 50 to 69 years old, the VI^Rich_BCAAT subtype significantly influences PnI (p = 0.05) but not survival (Log-rank test, z = 0.57, p = 0.57). V^Rich_BCAAT was significantly impactful for BC patient survival aged 70 to 75 years old (p = 0.043). BMI did not correlate with any of the BCAAT subtypes but was strongly correlated with prognostic markers for each BCAAT subtype. Conclusions: Based on immunohistochemically detected cellular and vascular components, four microscopic BCAAT subtypes were identified. Three of four BCCAT subtypes specifically affect BC patient prognosis and survival depending on age.

Background/Aim. We previously described four distinct breast cancer (BC)-associated adipose tissue (BCAAT) subtypes that have a significant impact on survival. In this exploratory study, we aimed to determine whether these BCAAT subtypes exhibit significant correlations with neoadjuvant and adjuvant therapies and BC molecular subtypes. Methods. Four BCAAT subtypes previously identified as fibroblast-rich (F^Rich_BCAAT), myofibroblast-rich (MyoF^Rich_BCAAT), vascular-rich (V^Rich_BCAAT), and mixed vascular- and inflammation-rich (VI^Rich_BCAAT) were analyzed according to their distribution in BC molecular subtypes, as well as in relation to neoadjuvant therapy and survival. Results. Triple-negative BC and Luminal B (LB) BC are related to V^Rich and VI^Rich BCAAT subtypes and were affected by Epirubicin/Cyclophosphamide (EC)+ paclitaxel (PTX) therapy, which significantly enhanced overall survival (OS) and disease-free survival (DFS). For the Luminal A (LA) BC subtype, EC + docetaxel (DTX) had significant impact on survival independent of BCAAT subtype. Conclusions. BCAAT subtypes strongly influenced neoadjuvant therapy response and survival depending on BC molecular subtype.