Abstract 2120: Human epidermal growth factor receptor 3 might be a targetable molecule for treatment of chemotherapy resistant breast cancer

Abstract

Abstract Introduction: Disease control of chemotherapy refractory breast cancer patients (CRBC), who do not respond to conventional treatment strategies, is important. In the setting of neoadjuvant chemotherapy (NAC), susceptibility of the chemotherapeutic agents could be confirmed with clinical relevance. Doxorubicin, docetaxel and paclitaxel have been used as conventional NAC. Eribulin and platinum may also be added in the future. When the drug sensitivity is evaluated by NAC and it is not sensitive to the drugs, there is currently no effective therapy expected to be improved. This is one of the recent unmet medical needs in breast cancer treatment strategy. Materials and Methods: In this study, in order to establish a novel therapeutic strategy for CRBC, we established chemotherapy resistant breast cancer cell lines against doxorubicin, paclitaxel, docetaxel and eribulin using BT549, Hs578t, MDA-MB231, MDA-MB468, and HCC70. We evaluated human epidermal growth factor receptor 3 (HER3) expression in these parental and resistant cell lines. We used U3-1402 (a novel anti-HER3 antibody-drug conjugate) to test if HER3 targeting treatment inhibits the cell proliferation of the chemotherapy resistant cell line with positive conversion of HER3 expression. Results: We found that the change to positive expression of HER3 in paclitaxel resistant BT549 cell line (BT549/PTX) and eribulin resistant Hs578t cell line (Hs578t/ERI) while these two cell lines initially showed negative expression of HER3. In the cell proliferation assay, as we expected, there was no inhibition of proliferation by treatment with HER3 targeting antibody agent U3-1402 in these two cell lines. However, BT549/PTX and Hs578t/ERI with positive conversion of HER3 expression were clearly inhibited their cell proliferation by treatment with U3-1402. Conclusions: It suggests that even in cases whose tumor does not express HER3 initially and show no response for chemotherapy in the NAC, U3-1402 could be effective for the patients with positive conversion of HER3 expression after NAC. We are studying for the role of positive conversion of HER3 expression in the process of acquired chemo-resistance and the elucidation of the molecular mechanism of positive conversion of HER3 expression in these unique treatment condition. Citation Format: Takeshi Kotake, Eiji Suzuki, Fengling Pu, Tatsuki Kataoka, Masahiro Hirata, Eri Hohokabe, Masakazu Toi. Human epidermal growth factor receptor 3 might be a targetable molecule for treatment of chemotherapy resistant breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2120.