Although c-MYC contributes to tamoxifen resistance, it improves cisplatin sensitivity in ER-positive breast cancer

Abstract

Tamoxifen (TAM) resistance is a major challenge in the treatment of estrogen receptor-positive (ER+) breast cancer. To date, to the best of our knowledge, there are only a few studies available examining the response of patients with TAM-resistant breast cancer to chemotherapy, and the guidelines do not specify recommended drugs for these patients. In the present study, TAM-resistant cells were shown to exhibit increased proliferation and invasion compared with the parent cells, and the increased expression of c-MYC was demonstrated to play an important role in TAM resistance. Furthermore, the TAM-resistant cells were significantly more sensitive to cisplatin compared with the parent cells, and the silencing of c-MYC expression desensitized the cells to cisplatin through the inhibition of the cell cycle. An increased c-MYC expression was observed in 28 pairs of primary and metastatic tumors from patients treated with TAM, and the clinical remission rate of cisplatin-based chemotherapy was significantly higher compared with other chemotherapy-based regimens in 122 patients with TAM resistant breast cancer. Taken together, the data of the present study demonstrated that although c-MYC was involved in TAM resistance, it increased the sensitivity of ER+ breast cancer to cisplatin. Thus, cisplatin may be a preferred chemotherapeutic agent for the treatment of patients with TAM-resistant breast cancer, particularly in patients where the rapid control of disease progression is required.