P5-01-03: Correlation between Aromatase Expression in Metastatic and Primary Breast Cancer.
Authors: Ribeiro JM , Luis IV , Correia L , Casimiro S , Fernandes A , Quintela A , Mestan J , Ramos M , Costa L 
Published: June 2012

Background: Estrogens are the major mitogenic factor in hormone dependent breast cancer. In postmenopausal women, estrogen production results mainly from extra-glandular conversion of androstenedione to estrone. This conversion is catalyzed by the enzyme aromatase (Aro). It is known that an higher expression and activity of the enzyme Aro is present in primary breast carcinoma compared with normal breast tissue. These data may indicate that tumors have the ability to produce their own estrogen. However, it is not known whether this process can occur at the level of metastasis. This study aims to determine the expression of aromatase in metastatic breast cancer and to analyze its correlation with expression at primary tumor and response to aromatase inhibitors (AI).

Material and Methods: We selected 41 patients with metastatic breast cancer, followed in the Department of Medical Oncology since 1995, undergoing surgery or biopsy of a metastatic lesion in the course of the disease (24 liver metastases; 10 bone metastases; 6 lung metastases; 1 lymph node metastases). For all these patients a detailed clinical chart review regarding clinical information (including treatment and tumor status) was obtained. Samples (formalin fixed and paraffin embedded) were analyzed for aromatase expression by immunohistochemistry (IHC), using the anti-aromatase monoclonal antibody # 677 (Novartis). Slides were scored considering the proportion of immunoreactive cells and intensity of the staining, and evaluating separately the epithelial and stromal component. The Fisher and log-rank test were used to determine the correlation between Aro expression in metastatic tissue and response to AI. Results: Aromatase was expressed in 51% (21/41) of the samples (13 liver metastases; 8 bone metastases). The average combined score was 130 (10 — 320). The average score was higher in the epithelial component versus the stromal component (123 vs. 17.5). There was a strong expression of Aro in bone metastases (average combined score: 176) compared with other sites.

There was no correlation between Aro expression and estrogen receptors expression. In 15 patients, it was also possible to evaluate the expression of Aro in the primary tumor. Aro was expressed in four cases (36%), with an average combined score of 52.5. The Aro expression between the primary tumor and metastasis was concordant in nine cases.

Thirty-four patients received AI to treat metastatic disease. The median time to progression (TTP) with AI in the entire population was 17.8 months. In the group of patients with Aro expression in metastasis, the median TTP in AI was 19.5 months, significantly higher than that obtained in the group without detectable Aro expression: 6.5 months (p = 0.045). The overall survival in the group with Aro expression was125 months and the 77 months in patients without Aro expression (p = 0.54).

Conclusions: Aromatase is expressed by metastatic tumor cells from breast cancer, with a positive and statistically significant correlation between its expression in the metastasis and the clinical benefit to IA. Its expression was higher in bone metastases compared with other sites of metastasis although this difference was not, in our study, statistically significant.

Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-03.