Although c­MYC contributes to tamoxifen resistance, it improves cisplatin sensitivity in ER­positive breast cancer.

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