[Cyclooxygenase 2 and breast cancer. From biological concepts to therapeutic trials]

Abstract

Cyclooxygenases (Cox) are prostaglandin synthetase enzymes which play a key role in mammary carcinogenesis. Several connections were demonstrated between Cox and a few oncogenes (v-src, v-Ha-ras, HER-2/neu, Wnt, p53 mutated), alimentary products (PUFAs), transcription factors (c-jun and c-fos), proapoptotic proteins [Bax et Bcl-x(L)] or antiapoptotic (Bcl-2), CYP19 aromatase gene, NFkappaB receptor (RANKL), angiogenesis (via VEGF, TXA2, oxid nitric synthetase, alphaVbeta3 integrin receptor), peroxisome gamma proliferator receptor (PPARgamma) and its ligand PGJ2 and with antitubuline chemotherapy drugs. No correlation of Cox2 expression with hormonal receptors was shown. In epidemiologic studies there is evidence of breast cancer risk reduction for women who take AINS for a long time. Alimentary factors like resveratrol or insaturated fat acid reduce Cox2 expression in animal and could be investigated in human studies. Clinical trials are planed with the anti Cox2 celecoxib for breast cancer prevention, in adjuvant setting, in metastatic situation combined with exemestane or antitubulin drugs or in neoadjuvant therapy.