Background: Patients with advanced triple negative breast cancer (BC) have limited treatment options and poor prognosis. At least 20% of triple negative BCs express estrogen receptor (ER) β, the second known isoform of the ER. ERβ binds estrogens and tamoxifen with a similar affinity to ERα and has 5 isoforms, but only ERβ1 is fully functional. There is no standardized method for measuring ERβ. Most published studies used antibodies to total ERβ and ERβ1 with immunohistochemistry (IHC) staining >10-20% or Allred scores to define positive. Two retrospective studies of the relationship between ERβ expression and tamoxifen in early BC have shown ERβ expression was significantly associated with better distant disease free survival and better overall survival in the tamoxifen treated ERα negative patients. This “proof of principle” study will determine the efficacy of tamoxifen in patients with triple negative but ERβ positive metastatic BC. Methods: This single arm phase II study has a Simon’s 2 stage optimal design. The primary end-point is objective response rate (complete and partial responses). Eligible patients have histologically or cytologically confirmed metastatic triple negative BC (ER and PR absent, HER2 ISH negative or IHC 0 or 1) and measureable disease as per RECIST 1.1. Consenting patients undergo central ERβ testing and confirmation of triple negative status on a metastatic biopsy sample. ERβ positive patients (ERβ1 nuclear staining with Allred score >4) are offered trial participation. Consenting patients receive tamoxifen 20mg per oral daily until disease progression, unacceptable toxicity or withdrawal of consent. If there are ≥2 responses in the first stage of 28 patients, an additional 38 patients will be accrued. Tamoxifen will be considered worthy of further research if there are ≥6 responses in the total 66 patients recruited. Progression free survival and clinical benefit rate will also be assessed.