ANZ1001 SORBET: Study of estrogen receptor beta and efficacy of tamoxifen, a single arm, phase II study of the efficacy of tamoxifen in triple-negative but estrogen receptor beta-positive metastatic breast cancer.

TPS1136 Background: Targeted therapies are needed for triple negative breast cancer (BC). ERβ is expressed in at least 20% of triple negative BCs. ERβ binds estrogen and tamoxifen with a similar affinity to ERα. ERβ has 5 isoforms but only ERβ1 is fully functional. ERβ expression has been shown to be significantly associated with improved distant disease free survival and better overall survival in tamoxifen treated ERα negative patients in retrospective studies. 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, being conducted by the Australia and New Zealand Breast Cancer Trials Group, has a Simon's 2 stage optimal design. The primary end-point is objective response rate (complete and partial responses). Progression free survival and clinical benefit rate will also be assessed. Eligibility criteria include 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. To date 12 potentially eligible patients have been screened for ERβ; 4 had Allred score >4 (although 2 of these subsequently proved to be ineligible for the trial), 7 had Allred scores <4 and 1 result is pending. 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. Current accrual is 1. Registered on ANZCTR (12610000506099).