Abstract P3-06-04: Modification and reversal of the aggressive behavior of triple negative breast cancer by caffeic acid phenethyl ester (CAPE)

Abstract

Abstract CAPE is the major active component of propolis, a widely available, safe, honeybee natural product with anti-inflammatory, antioxidant, and antitumor properties. We have previously shown diverse effects of CAPE in breast cancer. We postulated that CAPE may be useful in chemoprevention for women at high risk for triple-negative breast cancers (TNBC) and evaluated this in a radiation chimera mouse model in which the tumor spectrum is shifted to TNBC. The radiation chimera model consists of surgically clearing the mammary epithelium from the inguinal glands of 3-week old BALB/c mice, the mice were irradiated with 1 Gy or sham irradiated at 10–12 weeks of age, and bilaterally transplanted 3 days later with syngeneic Trp53 null mammary fragments. Mice were placed on a CAPE diet or a control diet at 1 month post transplantation that was maintained for the course of the experiment. Mammary tumor development was monitored by palpation for up to 18 months. The first tumor was resected at 1cm3 and mice monitored for tumor recurrence or second tumor formation. Tumors were immunostained for estrogen receptor (ER) status and ER negative tumors were selected from all the groups for RNA sequencing. No difference in body weight or tumor incidence was observed between mice on the CAPE versus control diet. Host irradiation significantly accelerated tumor growth rate compared to the control sham irradiated mice. CAPE treatment blocked this effect, but did not affect the control tumor growth rate. Resected tumors in CAPE treated mice recurred at significantly longer intervals (average of 40 days in the control group versus 90 days with CAPE treatment) and much less frequently than tumors from mice on a control diet. Mean expression analysis showed that CAPE induces a distinct gene expression pattern in ER negative tumors from irradiated mice. As previously described, the transcriptional profile of ER negative tumors was enriched in immune response genes in tumors from nonirradiated mice on a control diet, while irradiation suppresses these genes. Interestingly, this difference was abrogated in mice on the CAPE diet where we found that CAPE reverses the suppression of immune response genes in the ER negative tumors from the irradiated mice. These findings support the potential use of CAPE to modify the aggressive behavior of TNBC. This may be due to effects on the immune system in which CAPE acts to re-establish anti tumor immunity. Thus, CAPE may be useful in chemoprevention both for women at high risk for TNBC and to prevent or delay TNBC breast cancer recurrence. Citation Format: Omene C, Patel M, Illa Bochaca I, Barcellos-Hoff MH. Modification and reversal of the aggressive behavior of triple negative breast cancer by caffeic acid phenethyl ester (CAPE) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-06-04.