Determinants of breast cancer growth rate: exploring the role of histological grade features, tumor subtype, size, the presence of ductal carcinoma in situ and tumor‑infiltrating lymphocytes

Purpose: Breast cancer is a heterogeneous disease with well-established prognostic factors; however, in vivo tumor growth studies are rare. This study aimed to evaluate factors associated with tumor specific growth rate (SGR), including histological grade features and the presence of tumor-infiltrating lymphocytes (TILs). Methods: We conducted a retrospective cohort study including patients whose breast lesions were either missed on imaging examinations or who experienced a delay between breast cancer diagnosis and treatment. Tumor volume was calculated in the first and last abnormal imaging examinations. New histological slides were prepared for histologic and immunohistochemical evaluation. Results: Among the 89 lesions analyzed, the mean SGR (x10-2) was 0.31 (±0.28). On multivariate analysis, factors associated with faster tumor growth were: nuclear pleomorphism score of 3 compared to scores 1 and 2 (unstandardized B = 0.198; 95% confidence interval [CI], 0.097-0.300); triple-negative subtype versus other subtypes (B = 0.187, 95% CI, 0.024-0.350); and larger tumor size at the initial examination (B = 0.010, 95% CI, 0.004-0.016). The presence of ductal carcinoma in situ (DCIS) was associated with slower tumor growth (B = -0.120, 95% CI, -0.218- 0.022). On univariate analysis, tumors with ≥ 60% of TILs showed a marginally higher SGR compared with those with associated with ≤ 10% TILs (0.44 versus 0.26, p = 0.058). Conclusions: Several established breast cancer prognostic factors were associated with SGR. Higher nuclear pleomorphism, triple‑negative subtype, and larger initial tumor size were independently associated with faster tumor growth, whereas the presence of DCIS was associated with slower growth. Higher TIL levels were marginally associated with increased SGR, suggesting a potential role in breast cancer growth dynamics.