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 developing countries. The burden is increasing in low-income and middle-income countries (LMCs) and threatens the public health of such societies. Introduction of expensive monoclonal antibodies to cancer treatment regimens poses a real challenge in the health systems of LMCs. Despite controversy of cost-effectiveness of bevacizumab in breast cancer, some studies indicate gain of patients from this drug. The present study aimed to propose a priority setting model for administration of anti-angiogenic agents in breast cancer via assessment of tumor angiogenesis by the microvessel density (MVD) method and associations with clinicopathological characteristics (including simultaneous mutations of TP53 and HER-2 genes).


METHODS
Age, axillary lymph nodes status, tumor size, stage and grade, estrogen and progesterone receptors status, HER-2/neu status (by immunohistochemistry and FISH test), TP53 mutation, Ki-67 (for proliferation assay) and CD34 (for angiogenesis assay) were assessed in 111 breast cancer patients. The molecular subtype of each tumor was also determined and correlations of simultaneous mutations of HER-2 and p53 genes with angiogenesis and other clinicopathological characteristics were evaluated.


RESULTS
There were significant associations between simultaneous mutations of HER-2 and p53 genes and all other parameters except tumor size. The degree of angiogenesis in the ERBB2 subtype was greater than the others. Younger patients showed a higher angiogenesis rate rather those older than 50 years.


CONCLUSIONS
Our results demonstrated that patients with simultaneous mutations of HER-2 and p53 genes, those with ERBB2 molecular subtype and also younger women (often triple negative) seem more eligible for obtaining anti-angiogenic agents. These results suggest a model for priority setting of patients with breast cancer for treatment with anti-angiogenic drugs in LMCs.
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran E-mail : ekeyhani1058@gmail.com.
Elahe
E
Keyhani
Ahad
A
Muhammadnejad
Farkhondeh
F
Behjati
Fereidoon
F
Sirati
Faranak
F
Khodadadi
Masoud
M
Karimlou
Fatemeh A
FA
Moghaddam
Reza
R
Pazhoomand
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D018275:Carcinoma, Lobular / Q000098:blood supply / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human