Abstract P4-09-10: Prospective Analysis of Fatty Acid Synthase (FASN) in Breast Cancer Tissue of Early-Stage Breast Cancer Patients

Abstract

Abstract Background: Cancer cells require nutrients to survive in the unfavorable microenvironment of primary solid tumors or metastases before angiogenesis development. Fatty acid synthase (FASN) is a multi-enzyme protein that catalyzes fatty acid synthesis. Expression levels of FASN are low or undetectable in normal human tissues except for the liver and the adipose tissue. In contrast, high levels of FASN expression have been detected in breast cancer tumors and other human carcinomas. Several reports highlight that FASN overexpression in tumor samples correlates with progression, aggressiveness and metastatic potential of the disease. In adition, some studies have suggested the same correlation with serum levels of FASN. Our aim was to analyze the association between the expression of tumor and serum levels of FASN with clinical and pathological prognostic factors in early-stage breast cancer patients. Methods: Fifty-five patients with early-stage breast cancer treated with surgery and post-operative chemotherapy were included in the study. We prospectively measured the levels of FASN in tumor and serum samples. Clinical data included demographic characteristics, menarche, pregnancy, breast feeding, menopausal status and body mass index (BMI). Pathological and molecular data included: pathological state, histological grade, estrogen and progesterone receptors, HER2 status, p53 mutation and Ki 67 levels. FASN tissue expression levels were determined by IHC and circulating FASN levels were determined by ELISA. FASN expression was graded from 0 to 3+, meaning 0–1+ normal amounts of FASN protein compared to non-tumor breast tissue, 2+ moderate amounts and 3+ the highest levels of FASN expression. Baseline characteristics were summarized descriptively. Categorical variables were compared by c2 or Fisher's exact. For continuous variables, if the data are approximately normal, the two groups were compared using ANOVA. If the normality assumption is not warranted, then the Kruskall-Wallis test has been used. Results: Median age was 49 (rage 33–77). 51% of the patients were menopausal and median BMI was 24,75. Thirty-four percent of the patients had stage I, 51% stage II and 15% stage III. We observed a statistically significant association between FASN over expression and the lack of progesterone receptors (p = 0.027) in tumor samples. In contrast, we found no relation between FASN and estrogen receptor nor between FASN and HER2 tumor expression in this setting. Menopause and age were strongly related to higher levels of FASN tumor expression (p < 0.001). Patients with higher BMI had higher levels of FASN in tumor tissue although this association was not statistically significant (p = 0.07). Finally, we observed a positive relation between breast cancer stage and the levels of FASN tumor (p = 0.05). In contrast, circulating FASN levels were not associated with any pathological or clinical prognostic factor. Conclusions: Our study suggests that FASN overexpression is significantly related to age, menopausal status, more advanced stages and lack of progesterone receptor expression in early-stage breast cancer patients. However, no relation between serum levels of FASN and the clinical or molecular prognostic factors have been observed. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-10.