Abstract Background Currently, an anthracycline followed by a taxane as adjuvant or neoadjuvant chemotherapy is considered the most effective treatment for patients with triple-negative breast cancer. However, docetaxel followed by an anthracycline as neoadjuvant chemotherapy results in a higher rate of pathological complete response (pCR) than the regimen including an anthracycline followed by docetaxel (Iwata et al. Jpn J Clin Oncol 2011). Adjuvant docetaxel/cyclophosphamide (DC) treatment resulted in prolonged survival compared to adjuvant doxorubicin/cyclophosphamide. Therefore, we planned a phase II trial of DC followed by epirubicin/cyclophosphamide (EC) (Trial registration: UMIN000011031). Trial design This is a phase II trial to evaluate the efficacy and toxicity of DC followed by EC as neoadjuvant therapy for triple-negative breast cancer. Patients will receive four cycles of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) every 21 days, followed by four cycles of epirubicin (90 mg/m2) and cyclophosphamide (600 mg/m2) every 21 days. Eligibility criteria Patients with histologically diagnosed triple-negative breast cancer, T1–4, N1–3, or T2–T4, N0 based on a core needle biopsy, will be included in this trial. Eligible patients must be between 20 and 70 years of age with a performance status of 0–2 and adequate organ function. They must not have undergone any prior operation, radiation therapy, chemotherapy, endocrine therapy, or immunotherapy. Specific aims The primary endpoint is the pCR rate in the breast and axilla, and the secondary endpoints are the breast-conserving rate, toxicities, feasibility, and 5-year overall survival and relapse-free survival. pCR is defined as disappearance of invasive cancer cells, including those in the axilla, although the presence of residual intraductal cancer is acceptable. Statistical methods The sample size was calculated using the Simon method, with a type I error of 10% and a study power of 80%. The expected pCR rate is 25%, with a threshold pCR rate of 10%, and the required number of patients has been estimated to be 33. Present and target accrual Patient accrual within two medical centers was started in September 2013. We plan to enroll a total of 34 patients in the trial. Citation Format: Tanaka N, Hirano A, Inoue H, Ogura K, Hattori A, Jibiki N, Yukawa H, Matsuoka A, Kodera A, Kamimura M, Naritaka Y, Shimizu T. A phase II trial of neoadjuvant docetaxel/cyclophosphamide followed by epirubicin/cyclophosphamide for triple-negative breast cancer [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 OT1-01-02.