Background: Oral metronomic chemotherapy may target tumor cells indirectly via antiangiogenic activity, restoration of anticancer immune response, or induction of tumor dormancy. This phase II study (NCT01526499) aims to evaluate the efficacy of metronomic oral cyclophosphamide in addition to docetaxel as first-line therapy. Methods: Eligible patients with ER or PR positive or HER-2-overexpressed ABC who previously untreated were randomly assigned to receive docetaxel 75 mg/m²on day 1 with or without continuous oral cyclophosphamide 50mg daily in a 21-day cycle. Patients with HER-2-overexpressed tumors also receive trastuzumab. All patients received docetaxel until disease progression or unacceptable toxicity or withdrawal of consent. Maintenance endocrine and/or trastuzumab were allowed. The primary endpoint was PFS. Results: Between Dec 2011 and Nov 2012, 31 patients were randomized to docetaxel (T) group while 35 to cyclophosphamide plus docetaxel (Metro-TC) group. The majority of the patients (83.3%) were hormonal receptor positive; 31.8% were HER2 over-expressed; 84.8% had visceral metastasis and 48.5% had ≥3 metastatic organ sites. Patients’ characteristics were well balanced. Median treatment cycles of docetaxel for both groups were eight cycles. In intention-to-treat population with median follow-up of 18 months, median PFS was statistically longer in the Metro-TC group ( not reached) than it was in the T group (13.6 months, 95%CI, 7.0 to 20.2) (P =.04). Median OS had not been reached. The ORR were 51.6% (16/31) in the T and 71.4% (25/35) in Metro-TC group, respectively (P =.09). There was no significant difference of grade 3/4 toxicities between the two groups. Adverse effects were mainly docetaxel-related, including grade 3/4 neutropenia (100%) and febrile neutropenia (n=19, 29.2%). The only significant difference between the two treatment was mucositis (all grade, 10% versus 43%, P=0.003). Conclusions: The addition of metronomic cyclophosphamide to standard chemotherapy as first-line treatment for non-triple-negative ABC shows a benefit in PFS without significant increase in toxicity. Clinical trial information: NCT01526499.