276P - Biological and Clinical Implications of Aromatase Inhibitors for Neoadjuvant Therapy in Breast Cancer

Abstract

ABSTRACT Aim: Neoadjuvant aromatase inhibitors (AIs) therapy has become acceptable. Estrogens play a major role in promoting the growth of breast cancers (BCs). Androst-5-ene-3b,17b-diol (ADIOL) possesses estrogenic properties. Here we report the efficacy of AIs and the influence of letrozole (LET) on BC tissue and plasma levels of estrone (E1), estradiol (E2), estrone sulfate (E1S), ADIOL, and androstendione (AONE) in postmenopausal women undergoing neoadjuvant therapy for estrogen receptor (ER)–positive BCs. Methods: Twenty-nine postmenopausal patients with stage I (n = 3), IIA (n = 11), IIB (n = 5), IIIA (n = 2) and IIIB (n = 9) BCs were treated with anastrozole, LET or exemestane as neoadjuvant treatment. One patient had bilateral BC. Plasma and BC tissue samples were obtained from 9 patients before and after 4 months of neoadjuvant therapy with LET. Steroids concentrations were measured by liquid chromatography/ electrospray tandem mass spectrometry. Results: One of 30 tumors showed complete response (CR), 15 showed partial response (PR) and 14 showed stable disease (SD). All treatments were well tolerated. After treatment, a decrease of progesterone receptor expression was more frequent in responding tumors (93.8%) than in non-responding tumors (35.7%). Suppression of Ki67 after treatment was significantly greater in responding tumors than in non-responding tumors (P = 0.002). The mean BC tissue levels of E1, E2, E1S, ADIOL, and AONE at base line were 0.534, 0.409, 0.13, 1.65, and 6.09 pmol/g, respectively. After neoadjuvant therapy, the levels of E1, E2, E1S, ADIOL, and AONE were 0.002, 0008, 0.002, 2.22, and 5.63 pmol/g, respectively. The mean plasma levels of E1, E2, E1S, ADIOL, and AONE at base line were 621.5, 27.0, 1799.5, 1033, and 2258 pmol/l, respectively. After therapy, the levels of E1, E2, E1S, ADIOL, and AONE were 1.7, 1.6, 3.4, 1111, and 2826 pmol/l, respectively. LET significantly suppressed estrogens. Although plasma and tissue ADIOL levels were high after treatment, there was no progress disease in the 9 cases. With a median follow up of 69 months, there was no significant difference in overall survival between patients with CR or PR and those with SD. Conclusions: Neoadjuvant AIs therapy provided satisfactory efficacy and safety profiles. The activity of AIs was correlated with significantly reduced estrogens levels, but not with ADIOL levels. Disclosure: All authors have declared no conflicts of interest.