VEGF-dependent angiogenesis in therapeutic pathomorphosis of breast cancer

INTRODUCTION: The involvement of angiogenic factors in the tumor progression and invasion processes, in escape from immunological surveillance and alterations in the signal sensitivity implicates the perspectiveness of investigating VEGF-dependent angiogenesis in the context of therapeutic regression of breast cancer (BC).

AIM: To study the immunohistochemical features of angiogenesis markers: vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang2) and its receptor tyrosine kinase (Tie2), depending on the degree of breast carcinoma regression with the underlying neoadjuvant chemotherapy (NACT).

METHODS: The study included 65 patients with verified locally advanced breast cancer and 10 patients with proliferative fibrocystic disease. Breast cancer patients underwent NACT according to the following regimen: 5-fluorouracil 500 mg/m², adriamycin (=doxorubicin) 50 mg/m², cyclophosphamide (FAC) 500 mg/m². At the screening stage, a core needle biopsy of the breast tumor was performed, and an examination of the surgical material upon completion of NACT. The key marker for breast cancer, the human epidermal growth factor receptor-2 (Her2/neu), and angiogenesis markers (VEGF-A, Ang2, Tie2) were assessed using the immunohistochemical method, and morphological regression of the tumor was determined using the residual cancer burden (RCB) system.

RESULTS: The most common type of breast carcinoma is invasive ductal breast carcinoma, luminal A, Her2/neu-negative subtype. Immunohistochemical characteristics of breast carcinoma angiogenesis are independent of the morphological and surrogate molecular subtype of tumor. Parameters of angiogenesis activity (VEGF-A, Ang2, Tie2) are maximally expressed in patients with the proliferative fibrocystic disease and BC before the start of NACT. NACT produces a weak suppressive effect on the parameters of angiogenesis activity irrespective of tumor type.

CONCLUSION: Objectification of the obtained results and clarification of the specific angiogenesis features in BC patients undergoing neoadjuvant chemotherapy requires further investigation of this matter using additional molecular genetic methods. We believe it would be appropriate to conduct experimental studies of the effects of cytostatic agents in various regimens (including ultra-low doses), as well as to conduct additional studies on the role of integrins and Notch receptors.