In situ levels of oestrogen producing enzymes and its prognostic significance in postmenopausal breast cancer patients.

Background: The risk of developing breast cancer is strongly correlated with the overall exposure to oestrogen and most tumours are more or less dependent on oestrogen for their growth. A great majority of breast cancers occur after menopause when the ovaries have ceased to be functional, yet breast tumours in postmenopausal women maintain high intratumoural oestrogen concentrations, primarily through enzymatic conversion of androgenic precursors.

Patients: with a hormone dependent tumour generally receive the anti-oestrogen tamoxifen that mediate its anti-tumour effect by competing with oestrogen for binding to the oestrogen-receptor (ER). We therefore propose that the levels of oestrogen producing enzymes may affect the prognosis in postmenopausal breast cancer patients treated with tamoxifen.

Methods: We measured the mRNA and protein levels of aromatase and sulfatase by real-time PCR (n=161) and immunohistochemistry (n=131) in postmenopausal women with breast cancer.

Results: A significant better recurrence-free survival was detected in patients with weak or high protein expression of stromal aromatase (P=0.0008), as also demonstrated by a decreased relative risk (RR=0.50, CI=0.33-0.76, P=0.003). When we combined patients with weak and high stromal aromatase and selected only ER-positive patients, the improved prognosis was even more evident (P=0.0000) and was shown to be a significant prognostic factor in a multivariate Cox-model (HR=0.15, CI=0.06-0.39, P=0.000). The mRNA expression of aromatase and sulfatase, as well as the protein expression of sulfatase revealed no prognostic significance.

Conclusion: Protein expression of stromal aromatase may serve as a significant prognostic marker in ER-positive patients.