Angiogenesis Markers in Breast Cancer - Potentially Useful Tools for Priority Setting of Anti-Angiogenic Agents

Background: Breast cancer is the most common malignancy among women in both developed and developingcountries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens thepublic health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimensposes a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumabin breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose apriority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumorangiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics(including simultaneous mutations of TP53 and HER-2 genes). Materials and
Methods: Age, axillary lymphnodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (byimmunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesisassay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined andcorrelations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathologicalcharacteristics were evaluated.
Results: There were significant associations between simultaneous mutations ofHER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than50 years.
Conclusions: Our results demonstrated that patients with simultaneous mutations of HER-2 and p53genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligiblefor obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breastcancer for treatment with anti-angiogenic drugs in LMCs.