Aromatase inhibitors in ovarian cancer: is there a role?

Abstract

Estrogen plays a role in ovarian tumorigenesis. Aromatase is the enzyme required for the synthesis of estrogen via conversion of androgen to estrogen, which is the major source of estrogen in postmenopausal women. Aromatase is present in normal ovaries and other tissues (e.g., fat and muscle) as well as in 33-81% tumor tissues of ovarian cancer. Aromatase inhibitors (AIs) block estrogen synthesis by inhibiting aromatase activity. In patients with recurrent ovarian cancer, single-agent AI therapy has been shown to elicit clinical response rates of up to 35.7% and stable disease rates of 20-42%. Given the limited treatment options for recurrent ovarian cancer and the favorable safety profile and convenient use, AI is a rational option for prolonging platinum-free interval in recurrent ovarian cancer. Further studies are required to determine the efficacy of combination treatment with AIs and biological agents, determine the benefit of AIs for treating special types of ovarian cancer (e.g., endometrioid type), and identify biomarkers for targeted patient selection. This review summarizes the current epidemiologic, preclinical, and clinical data regarding estrogen's role in ovarian cancer, the expression and regulation of aromatase in this disease, the development and characteristics of the three generations of AIs, and the preclinical and clinical studies of AIs in the treatment of ovarian cancer.

Aromatase Imaging with [N-Methyl-11C]Vorozole PET in Healthy Men and Women

“…Our results provide baseline information for future studies in neuropsychiatric disorders and cancer (24,25). We show that 11 C-vorozole is taken up by all major organs in humans, as would be expected on the basis of the reportedly widespread expression of Cyp19A1 in human organs, systems, and cell types, controlled by a large number of tissuespecific promoters (26).…”

“…33%-80% of ovarian tumors (25). Further studies of 11 C-vorozole uptake in the premenopausal ovary may establish a role for aromatase imaging in the diagnosis and treatment management of other endocrine reproductive disorders.…”

Estrogen receptor gene amplification occurs rarely in ovarian cancer

“…Monotherapy studies using tamoxifen, aromatase inhibitors, and GnRH analogues had yielded variable results with objective response rates ranging between 0 and 56%. 17,[19][20][21][34][35][36][37][38] Combinatorial treatment regimens combining tamoxifen and goserelin or tamoxifen and Gefitinib had obtained results with objective response rates of up to 11.5%. 39,40 Few of these studies had selected patients based on the immunohistochemically determined estrogen receptor status.…”

Telomerase in the ovary

“…During multi-step ovarian carcinogenesis, many alterations occur in the interactive network of estrogenresponsive genes, including the proto-oncogene MYC, anti-apoptotic protein BCL2, and TERT (Chow et al 1996). These estrogen-regulated genes may play important roles during ovarian tumorigenesis, such as aberrant epithelial cell proliferation, immortalization, transformation, invasion, and metastasis (Li et al 2008; Fig. 1).…”